Medicines & Treatments
Selank (10mg)
Selank is a short, synthetic heptapeptide composed of seven amino acids. Selank was developed to mimic the naturally occurring peptide Tuftsin,(5) a short fragment from the immunoglobulin G (IgG), a natural tetrapeptide involved in certain biological functions that regulate the immune system. After the discovery and initial isolation of Tuftsin, researchers suggested that the peptide might be involved in the functions of phagocytic cells, including phagocytosis, motility, and immunological cell functions.(2) Since then, various synthetic analogs of Tuftsin have been synthesized in laboratories by conventional and polymeric reagent methods.(4) Overview Selank is a peptide chain composed of two fragments – one is Tuftsin at the N-terminus, and the other is a tripeptide Pro-Gly-Pro (PGP) at the C-terminal end of the molecule. The inclusion of a Pro-Gly-Pro (PGP) sequence in the peptide Selank might enhance its potential to penetrate various biological barriers, including the blood-brain barrier (BBB). The BBB is a highly selective and semi-permeable membrane that delineates the circulating blood from brain tissues and extracellular fluid within the central nervous system. It is deemed to play a pivotal role in controlling the entry of molecules. Integrating the PGP sequence might modify the peptide's hydrophilicity or lipophilicity, which might increase its compatibility with the lipid-rich milieu of the BBB. Moreover, the PGP motif might interact with certain transport systems or receptors on the BBB membrane, potentially facilitating receptor-mediated endocytosis or active transport. These mechanisms may permit Selank to circumvent the tight junctions that typically impede the transit of larger molecules through the BBB. Additionally, the presence of the PGP sequence might alter the tertiary structure of Selank, potentially rendering it more amenable to traversing the BBB. This alteration might arise from changes in the peptide's spatial configuration, which may influence its interaction with the cellular components of the BBB.(6) Chemical Makeup Molecular Formula: C33H57N11O9 Molecular Weight: 751.88 g/mol Other Known Titles: TP-7, Selanc Research and Clinical Studies Selank Peptide and BDNF Levels There is a possibility that Selank may influence the expression of brain-derived neurotrophic factor (BDNF), deemed a crucial protein in the brain that supports neuronal survival and growth.(1) Research indicates that Selank may markedly increase the levels of BDNF mRNA in the hippocampus, an integral region of the brain involved in memory and emotional responses. The potential of Selank to boost BDNF expression, particularly under conditions where stress and glucocorticoids suppress BDNF levels, suggests its relevance in research studies within the context of neuroplasticity decline. This protein's perceived role in synaptic function and neuronal adaptation underscores the significance of such investigations. Selank Peptide and Serotonin Signaling Selank may potentially influence serotonin signaling mechanisms. Serotonin signaling is theorized to play a crucial role in the management of mood and anxiety within the brain. Research utilizing murine models where serotonin synthesis was inhibited has indicated that Selank might be able to alter serotonin levels in cases where the serotonergic system is impaired. It has been proposed by researchers that Selank may potentially boost serotonin metabolism in the brainstem, indicating its potential action on the serotonin system. More specifically, the peptide is thought to facilitate an increase in the metabolic processing of serotonin in brain regions considered essential for mood and anxiety regulation. Additionally, the hypothesis that Selank may enhance serotonin metabolism suggests a potential pathway by which Selank might ameliorate issues stemming from diminished serotonin activity. Selank Peptide and GABA Signaling Studies have suggested that Selank may act on the gamma aminobutyric acid (GABA) receptors. GABA is considered an inhibitory neurotransmitter within this context, playing a role in diminishing neuronal excitability, fostering relaxation, and mitigating anxiety observations, as observed in animal research models. In one study,(7) the expression of 84 genes involved in neurotransmission was studied in murine models. The experimental murine models were exposed to either Selank or GABA, and gene expression was studied after one and three hours via a PCR method. All the gene expressions studied for Selank and GABA appeared positively correlated. The results suggested that Selank had the potential to induce several alterations in the neurotransmission process, suggesting by proxy that Selank may exert possible action via modulating the GABAergic system. Moreover, the literature indicates that the influence of Selank might not be confined to mere direct actions on the transcriptional activity of genes associated with GABA receptors. It might also involve allosteric modulation of the GABAergic system. This is inferred from observed variations in gene expression following exposure to Selank compared to GABA, where Selank has been speculated to distinctly affect the expression of specific genes. Such differential gene expression alludes to a more complex interaction of Selank with the GABAergic system, possibly diverging from the direct receptor activation typically seen with GABA. Selank has also been proposed to instigate enduring modifications within neurotransmitter systems, a characteristic that might account for its extended anxiolytic actions observed in experimental frameworks. These alterations suggest a broader and potentially long-term impact on neurotransmitter dynamics beyond potential receptor interaction, emphasizing the complex potential of Selank on neural regulation. Selank Peptide and Genome Expression Studies have been conducted to understand the potential of Selank peptide on genome expression and its involvement in the inflammatory process. These studies(8) were conducted on male murine models weighing 250 grams. These murine models were separated into three groups – a control group, an experimental group with a single exposure to Selank, and an experimental group under routine exposure to Selank. After the study, the RNA was isolated from the rat spleen and hippocampus and studied via PCR method. Based on the results, it was suggested by the researchers that Selank might have the potential to impact gene expression, exhibited more definitively in the spleen and the hippocampus. One of the gene expressions reported during the study was the change in CX3CR1, which was involved in the inflammatory process. This suggested that Selank might regulate the inflammatory process through the mechanism of gene expression, mainly the CX3CR1 alteration. Selank Peptide and Enkephalin Signaling In a clinical study,(9) 62 research models of Generalized Anxiety Disorder (GAD) were examined. These models were divided into two groups – 48% were exposed to Selank, whereas 52% were exposed to a generic benzodiazepine compound. Following the study, the psychometric levels of all models were analyzed. Results suggested that the impact of Selank appeared to be similar to those of the generic compound. Researchers also reported that enkephalin levels of tau leu-enkephalin were apparently reduced in the Selank-exposed group before the experiment, and the addition of Selank may have reversed this observation. Selank is hypothesized to exert suppressive actions on enzymes that break down enkephalins. Enkephalins, which are endogenous ligands for opioid receptors, have been implicated in the regulation of pain, mood, and stress responses. Therefore, the potential inhibition of these degrading enzymes by Selank might result in increased levels of enkephalins, potentially augmenting their physiological actions. This could lead to a noticeable elevation in tau(1/2) leu-enkephalin concentrations during experiments involving anxiety models where Selank is evaluated. Selank Peptide and Memory This study(11) was conducted on murine models that were enrolled in a "training" session of four days for learning conditioned avoidance response (CAR). CAR is a learned response in delaying or preventing avoidance behavior. Selank exposure was begun 15 minutes before the training session on all four days. Upon monitoring the behavior of the murine models, researchers suggested that the learning abilities of the murine models appeared to improve with each exposure of the peptide, as the number of errors reduced and the number of correct solutions increased. This potential impact might be mediated through multiple interconnected pathways, including the modulation of neuropeptide systems within the brain. These neuropeptides are deemed critical as they are believed to play significant roles in various cognitive functions, potentially boosting processes related to learning and memory. Additionally, the peptide Selank might alter neural circuits involved in memory consolidation. This alteration may enhance synaptic stability and efficiency in learning processes. Moreover, Selank might indirectly boost cognitive performance by mitigating anxiety-related factors that frequently impede learning efficiency. This suggests that Selank may influence the emotional aspects of cognition, enhancing the overall cognitive process. Furthermore, Selank may promote neural plasticity or the capacity of neurons to adapt, particularly in cognitive circuits that are not performing optimally, thus potentially elevating their function. This enhancement of neural adaptability may be vital for the maintenance and improvement of cognitive abilities, suggesting that Selank might be a valuable compound for further research in neurocognitive fields. Selank Peptide and Immunomodulation This clinical study(12) was conducted on research models of GAD with neurasthenia, with a control group and experimental group exposed Selank peptide for 14 days. After the study, the peripheral blood samples were collected and analyzed. The analytical results suggested peak elevation in the levels of IL-6 cytokine and changes in the Th1 and Th2 cytokine ratio, all of which are believed to regulate the immune system. Selank Peptide and Withdrawal In this study,(13) murine models were infused with 10% ethanol as their sole fluid source for 24 weeks. Consequently, these murine models were experimentally induced with alcohol withdrawal symptoms once the ethanol drip was removed. The murine models were then exposed to Selank, to study its potential impact on the withdrawal symptoms. After 48 hours, researchers reported that the alcohol withdrawal symptoms appeared to have reduced, based on the results of their social interaction and maze tests. Selank Peptide and Cardiovascular Activity In this study,(14) Selank was presented to feline models. The main goal of this study was to examine the cardiovascular and respiratory potential of the peptide in this specific model. Upon exposure to the peptide, it was reported by the researchers that there appeared to be a 32% decrease in arterial blood pressure within 3 minutes of peptide presence. Moreover, the peptide possibly induced a 24% increase in cerebral blood flow within the first 10 minutes, slowly decreasing to optimal levels. Selank was not reported to have induced any action on the respiratory system or the heart rate. Selank Peptide and Weight, Cholesterol In this study,(15) murine models were first exposed to a high-fat diet for 6 consecutive weeks until the weights of murine models were measured between 280g to 300g. Later, these murine models were divided into two groups, a control group given sodium chloride, and an experimental group exposed to Selank peptide. Additionally, a group of control murine models were used for this study, which were not presented with either of the agents but were simply monitored for the purpose of the study. Upon analysis, it was suggested by the researchers that the Selank group exhibited apparently decreased levels of cholesterol and fat anywhere between 25% and 58%. Based on the findings, Selank may also reduce specific forms such as low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) cholesterol, and triglycerides. This indicates that Selank might play either a direct or an indirect role in influencing the mechanisms of lipid metabolism and could potentially display actions that lower cholesterol (hypocholesterolemic) and lipid levels (hypolipidemic). Moreover, the investigation noted discernible enhancements in parameters related to hemostasis, including elevated total fibrinolytic activity and decreased platelet aggregation, which may suggest improvements in conditions that favor clot formation. Additionally, the study points to a possible modulatory action of Selank on glucose homeostasis, which involves maintaining stable blood glucose levels. The fat metabolism rate of the Selank group also was reportedly improved and was eventually measured at the same rate as those in control models. Upon weight determination of the murine models, it was noted that the control group exhibited an average weight gain of 40g throughout the study, whereas the experiment group maintained the same weight throughout the study, with gradual weight reduction upon peptide presentation. Selank peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Inozemtseva, L. S., Karpenko, E. A., Dolotov, O. V., Levitskaya, N. G., Kamensky, A. A., Andreeva, L. A., & Grivennikov, I. A. (2008). Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections, 421, 241–243. https://doi.org/10.1134/s0012496608040066 Najjar VA. Tuftsin, a natural activator of phagocyte cells: an overview. Ann N Y Acad Sci. 1983;419:1-11. doi: 10.1111/j.1749-6632.1983.tb37086.x. https://pubmed.ncbi.nlm.nih.gov/6370072/ Semenova, T. P., kozlovskiĭ, I. I., Zakharova, N. M., & Kozlovskaia, M. M. (2009). Eksperimental'naia i klinicheskaia farmakologiia, 72(4), 6–8. Fridkin M, Stabinsky Y, Zakuth V, Spirer Z. Tuftsin and some analogs: synthesis and interaction with human polymorphonuclear leukocytes. Biochim Biophys Acta. 1977 Jan 24;496(1):203-11. https://pubmed.ncbi.nlm.nih.gov/576412/ Kozlovskaya MM, Kozlovskii II, Val'dman EA, Seredenin SB. Selank and short peptides of the tuftsin family in the regulation of adaptive behavior in stress. Neurosci Behav Physiol. 2003 Nov;33(9):853-60. https://pubmed.ncbi.nlm.nih.gov/14969422/ Elena Filatova et al., GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells. https://doi.org/10.3389/fphar.2017.00089 Volkova, A., Shadrina, M., Kolomin, T., Andreeva, L., Limborska, S., Myasoedov, N., & Slominsky, P. (2016). Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission. Frontiers in pharmacology, 7, 31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757669/ T.A Kolomin et al., Transcriptomic Response of Rat Hippocampus and Spleen Cells to Single and Chronic Administration of the Peptide Selank. June 2, 2009. DOI: 10.1134/S1607672910010023 Zozulia AA, Neznamov GG, Siuniakov TS, Kost NV, Gabaeva MV, Sokolov OIu, Serebriakova EV, Siranchieva OA, Andriushenko AV, Telesheva ES, Siuniakov SA, Smulevich AB, Miasoedov NF, Seredenin SB. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(4):38-48. Russian. https://pubmed.ncbi.nlm.nih.gov/18454096/ Medvedev VE, Tereshchenko ON, Israelian AIu, Chobanu IK, Kost NV, Sokolov OIu, Miasoedov NF. A comparison of the anxiolytic effect and tolerability of selank and phenazepam in the treatment of anxiety disorders. Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114(7):17-22. Russian. https://pubmed.ncbi.nlm.nih.gov/25176261/ Kozlovskii II, Danchev ND. The optimizing action of the synthetic peptide Selank on a conditioned active avoidance reflex in rats. Neurosci Behav Physiol. 2003 Sep;33(7):639-43. https://pubmed.ncbi.nlm.nih.gov/14552529/ Uchakina ON, Uchakin PN, Miasoedov NF, Andreeva LA, Shcherbenko VE, Mezentseva MV, Gabaeva MV, Sokolov OIu, Zozulia AA, Ershov FI. Immunomodulatory effects of selank in patients with anxiety-asthenic disorders. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(5):71-5. Russian. https://pubmed.ncbi.nlm.nih.gov/18577961/ Kolik LG, Nadorova AV, Kozlovskaya MM. Efficacy of peptide anxiolytic selank during modeling of withdrawal syndrome in rats with stable alcoholic motivation. Bull Exp Biol Med. 2014 May;157(1):52-5. https://pubmed.ncbi.nlm.nih.gov/24913576/ Gan'shina TS, Kozlovskiĭ II. [Effects of the new peptide anxiolytic drug selank on the cardiovascular system functioning and respiration in cats]. Eksp Klin Farmakol. 2005 Jul-Aug;68(4):33-5. Russian. https://pubmed.ncbi.nlm.nih.gov/16193654/ N.F. Mjasoedov et al, The Influence of Selank on the Parameters of the Hemostasis System, Lipid Profile, and Blood Sugar Level in the Course of Experimental Metabolic Syndrome. April 14, 2014. Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Livagen (20mg)
Livagen is a short peptide containing four amino acids: lysine, alanine, aspartic acid, and glutamic acid. Considered to be a bioregulator, this peptide may act on the DNA structure and impact functionality. The primary potential of Livagen is identified in how it acts on chromatin, DNA, and genes. Scientists have formalized that DNA is a double helix structure surrounded by proteins called "histones." These histones bind together, forming chromatin, and several chromatins then condense together, forming the chromosomes. These chromosomes appear crucial to forming genetic material specific to each organism.(1) Livagen has been considered by researchers for its potential to 'de-condense' these chromatin materials. As a result, some genes that had become non-functional might become active, possibly improving cell activity and production.(2) Researchers posit that Livagen may increase energy levels and skin elasticity and possibly induce improvements in immune system functionality via this mechanism. Researchers have suggested that the lipid peptide acts on the lymphocytes, possibly reactivating the ribosomes by 'unpacking' the chromatin and modifying gene expression. These lymphocytes are white blood cells that are deemed essential in attacking foreign impurities entering the system and enhancing immunity. In this manner, Livagen may exhibit potential to improve the immune system by coordinating cellular responses and controlling inflammatory responses.(3) T. Lezhava et al., who conducted a clinical research study stated that “These results indicate that peptide bioregulators Epitalon, Livagen, and Vilon cause activation (deheterochromatinization) of chromatin in lymphocytes of [aged models].” Chemical Makeup Molecular Formula: C18H31N5O9 Molecular Weight: 461.5 g/mol Other Known Titles: KEDA Research and Clinical Studies Livagen and Gene Regulation Cardiac disorders such as hypertrophic cardiomyopathy (HCM), atherosclerosis, and cardiac injury are considered to be characterized by dysregulation in gene expression and chromatin structure. A bioregulatory peptide such as Livagen has been suggested by researchers to enact potential mitigation of such gene regulation dysfunctions. Studies(4,5) have suggested that Livagen peptides may help reduce specific long-term impacts of such conditions when applied to cell culture models of HCM. A publication related to the same study(6) also reported on the potential of the peptide’s exposure in the presence of cobalt ions to evaluate their combined potential on chromatin structures in experimental models of hypertrophic cardiomyopathy. The study suggested that this combination possibly induces the de-condensation of chromatin. The results of this study are stated to be critical “because it provides new information about the protective effect of Livagen and Livagen + Cobalt ions on the lymphocytes” in hypertrophic cardiomyopathy models.(6) Livagen, either alone or in combination with cobalt ions, appears to modify the activity of nucleolar organizer regions (NORs) and the associative behavior of acrocentric chromosomes. The study posits that the combined application of Livagen and cobalt ions increases frequency, scoring 2 NORs, which are integral to ribosomal RNA synthesis. Such an action on NORs may indicate enhanced or altered protein synthesis capabilities in these cells, which might be crucial in understanding how cellular function is modified in the context of cardiac hypertrophy seen in HCM. Additionally, an increase in the association of acrocentric chromosomes was noted, which is speculated to be more pronounced with the combined exposure of Livagen and cobalt ions compared to each agent alone. This phenomenon might reflect changes in the chromatin state, specifically the decondensation of heterochromatin. The study suggests that this chromatin remodeling might facilitate the exposure and possible transcriptional activation of previously inactivated genes within these regions. Livagen and Nociception Enkephalins are considered to be naturally occurring neurotransmitters that may bind with mu- and delta- receptors and reduce pain signal transmission. Bioregulatory peptides such as Livagen may possibly act on enzymes and prevent the degradation of these neurotransmitters, possibly increasing enkephalin levels. The activity of these degrading enzymes was assessed in vitro, based on the rate of hydrolysis of 3H-Leu-enkephalin, a labeled enkephalin peptide.(7) The study also explored whether Livagen might interact directly with mu- and delta- receptors in the brain, using a radioreceptor method with the tracer [3H][D-Ala2, D-Leu5]-enkephalin. This component of the study posited that there appeared to be no observable interaction between Livagen and the mu- or delta-opioid receptors of the membrane fraction from murine models' brains. This outcome suggests that while Livagen may influence opioid peptide levels by inhibiting their degradation, it does not appear to directly bind or affect opioid receptors in the brain. Livagen and Antioxidant Systems A study explored the potential hepatoprotective and immunoprotective properties of the Livagen, particularly in liver fibroid induration and both acute and chronic hepatitis models. The findings suggest that Livagen may help normalize immune response and antioxidant status, which might restore liver function during episodes of hepatitis, particularly in cases where liver function typically declines. Livagen potentially offers positive actions in mitigating liver fibroid induration and combating various forms of hepatitis, though the exact mechanisms of action remain unclear.(8) Livagen and DNA Repair DNA alteration over time is considered to lead to increased chromatin condensation and decreased cellular repair.(9) Researchers have suggested the Livagen peptide to inhibit and possibly reverse these alterations, improving cellular functions and 'reversing' cell aging.(3) Thus, specific chromosomal abnormalities may also be addressed through Livagen based on the exact mechanism. However, no direct studies have been conducted. Livagen peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: National Human Genome Research Institute. Chromatin. May 10, 2022. https://www.genome.gov/genetics-glossary/Chromatin Khavinson VKh, Lezhava TA, Monaselidze JG, Dzhokhadze TA, Dvalishvili NA, Bablishvili NK, Ryadnova IY. Effects of Livagen peptide on chromatin activation in lymphocytes from old people. Bull Exp Biol Med. 2002 Oct;134(4):389-92. https://pubmed.ncbi.nlm.nih.gov/12533768/ Lezhava T, Monaselidze J, Kadotani T, Dvalishvili N, Buadze T. Anti-aging peptide bioregulators induce reactivation of chromatin. Georgian Med News. 2006 Apr;(133):111-5. PMID: 16705247. https://pubmed.ncbi.nlm.nih.gov/16705247/ Dzhokhadze Ta et al., Functional regulation of genome with peptide bioregulators by hypertrophic cardiomyopathy (by patients and relatives), December 1, 2013. https://www.semanticscholar.org/paper/Functional-regulation-of-genome-with-peptide-by-(by-Ta-TZh/ddda519986d5793a0aedc2293f00f0e5fa540b4d Lezhava T et al., Activation of pericentromeric and telomeric heterochromatin in cultured lymphocytes from old individuals, 01 Apr 2007. https://europepmc.org/article/MED/17460203 [Effect of peptide bioregulator and cobalt ions on the activity of NORs and associations of acrocentric chromosomes in lymphocytes of patients with hypertrophic cardiomyopathy and their relatives]. Georgian Med News. 2014 Sep;(234):134-7. Russian. https://pubmed.ncbi.nlm.nih.gov/25341254/ Kost NV, Sokolov OIu, Gabaeva MV, Zolotarev IuA, Malinin VV, Khavinson VKh. Vliianie novykh peptidnykh bioreguliatorov livagena i épitalona na énkefalindegradiruiushchie fermenty syvorotki krovi cheloveka [Effect of new peptide bioregulators livagen and epitalon on enkephalin-degrading enzymes in human serum]. Izv Akad Nauk Ser Biol. 2003 Jul-Aug;(4):427-9. https://pubmed.ncbi.nlm.nih.gov/12942748/ Kuznik BI, Khasanova NB, Ryzhak GA, Mezsheriakova IE, Khavinson VK. [The influence of polypeptide liver complex and tetrapeptide KEDA on organism physiological function in norm and age-related pathology.]. Adv Gerontol. 2020;33(1):159-164. Russian. PMID: 32362099. Lezhava TA. Funktsional'nye osobennosti khromosom cheloveka i starenie [Human chromosome functional characteristics and aging]. Adv Gerontol. 2001;8:34-43. Russian. PMID: 11582753. https://pubmed.ncbi.nlm.nih.gov/11582753/ Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Ovagen (20mg)
Ovagen, also known by its sequence Glu–Asp–Leu (EDL), is classified among the short regulatory peptides that are proposed to act as genome-level bioregulators.(1) Within this conceptual framework, these compounds are often referred to as cytomedines, aka peptide messengers that may operate as independent signaling molecules, helping cells adapt their functional programs to internal and external cues. Within this broader family, Ovagen has been described by experts as a tripeptide that may form complexes with d(ATATATATAT )sequences located in the minor groove of DNA. It is proposed that this peptide may bind preferentially to AT-rich stretches of mammalian DNA in the minor groove, where many regulatory interactions usually occur. Through these types of interactions, Ovagen is suggested to interact with the expression of genes encoding cellular aging markers and other regulators of cellular stress responses. In vitro data from renal and hepatic models further suggest that Ovagen may display protective potential, possibly by modulating gene expression programs linked to proliferation, redox balance, and cellular resilience. Chemical Makeup Other Known Titles: EDL; H-Glu-Asp-Leu-OH Molecular Weight: 375.37 g/mol Molecular Formula: C15H25N3O8 Research and Clinical Studies Ovagen Research in Cellular Aging Further research by Khavinson et al. describes Ovagen as having possible geroprotective actions on aging kidney (renal) cell cultures.(2) When added to both young and aged renal cells, Ovagen apparently increases cell proliferation while at the same time reducing the expression of several cellular aging-associated markers. Ovagen associates with specific AT-rich DNA regions, possibly modulating the transcription of genes related to p16, p21, p53, and SIRT6, and thereby may shift the balance of renal cells away from senescence and toward renewed proliferative capacity under in-vitro conditions. These proteins are described in the paper as markers of cellular aging, so their downregulation in the presence of Ovagen may indicate a partial shift away from a senescent-like state toward a more proliferative phenotype. In parallel, Ovagen is reported to increase the expression of SIRT6 in renal cell cultures. Because the authors state that “the reduction of SIRT-6 synthesis in cells is one of the causes of cell senescence”, and the observed upregulation of SIRT6 in response to Ovagen is posited as a key element of its potential geroprotective activity at the cellular level. Taken together, within the limits of this single cell-culture study, Ovagen potential is described as a combination of better-supported proliferation, reduced expression of classical cellular aging markers, and increased expression of SIRT6. Ovagen Research in Kidney Cells Further research by Zamorskii et al in kidney cells suggests that Ovagen may induce a reduction in tubular water reabsorption by around 2.9% and a 1.6-fold rise in sodium excretion, while absolute and relative sodium reabsorption and proximal sodium transport remained stable.(3) The authors also noted that “EDL increased distal sodium transport by 1.2–1.3 times.” At the same time, the experiment by Zamorskii et al. reveals that the distal sodium transport apparently increased, and the correlations that describe glomerulo-tubular and tubular–tubular balance were preserved. Researchers such as these have suggested that Ovagen may shift distal tubular handling of sodium and water without disrupting intrinsic intrarenal autoregulation. Histological assessment after Ovagen exposure revealed no negative consequences in aged renal cells studied in laboratory settings. The study also suggests that Ovagen may relevantly support the prooxidant–antioxidant balance in aged kidney cells. Ovagen was associated with reduced lipid peroxidation and a decrease in oxidatively modified proteins. At the same time, catalase and glutathione peroxidase activities both increased, with the rise in glutathione peroxidase activity being especially pronounced compared to control laboratory models. This pattern is posited as a potential attenuation of oxidative stress in renal cells. Thus, Ovagen may modestly support water and sodium excretion via tubular mechanisms, adjust distal sodium handling, and possibly dampen oxidative damage in kidney cells, all while apparently preserving normal intrarenal regulatory relationships and baseline histoarchitecture. Ovagen Research in Liver Cells Further experimental work, largely reported in the patent by Khavinson et al. and earlier liver-cell investigations, describes Ovagen as a tripeptide with potential hepatoregenerative and hepatoprotective actions under laboratory conditions.(4) In liver cell systems, Ovagen was observed to possibly prolong the survival of liver cells while at the same time stimulating the growth of neoplastic liver tissue, which the authors interpret as an indication of its capacity to modulate hepatic cell proliferation. In parallel, murine models of liver regeneration after partial hepatectomy and experimental cirrhosis suggest that Ovagen apparently increases the proportion of dividing cells in regenerating liver tissue, may support biochemical markers associated with liver injury, and potentially increases hepatic glycogen content. Ovagen’s potential mechanisms behind these actions may involve interacting with genomic targets and thereby modulating the expression of genes that control proliferation, stress responses, and metabolic pathways in hepatic cells. Ovagen peptide is available for research and laboratory purposes only. Please review our Terms and Conditions before ordering. References: Khavinson, Vladimir Khatskelevich, et al. "Peptide regulation of gene expression: A systematic review." Molecules 26.22 (2021): 7053. Khavinson VKh, Tarnovskaia SI, Lin'kova NS, Poliakova VO, Durnova AO, Nichik TE, Kvetnoĭ IM, D'iakonov MM, Iakutseni PP. [Tripeptides slow down the aging process in renal cell culture]. Adv Gerontol. 2014;27(4):651-6. Russian. PMID: 25946838. Zamorskii, I. I.; Shchudrova, T. S.; Zeleniuk, V. G.; Linkova, N. S.; Nichik, T. E.; Khavinson, V. Kh. (2019). The Influence of Peptides on the Morphofunctional State of Kidneys in Old Rats. Advances in Gerontology, 9(1), 75–80. doi:10.1134/S207905701901017X Khavinson, Vladimir Khatskelevich, et al. "Пептид, стимулирующий регенерацию ткани печени, фармацевтическая композиция на его основе и способ ее применения." in Russian (2007). Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
BPC-157 (5mg / 10mg)
The BPC-157 peptide, also known as Pentadecapeptide BPC 157 or Body Protection Compound 157, is a synthetic compound that has been suggested in various studies to assist with healing joint, tendon, and muscle tissue, as well as nerve tissue. BPC-157 is a peptide composed of 15 amino acids with potential protective properties. As the name suggests, Body Protection Compound (BPC) is an amino acid fragment isolated from gastric juice.(1) BPC-157 is also commonly known as pentadecapeptide due to the 15 amino acids it is comprised of.(1) Overview BPC-157 has been steadily researched for its potential in wound healing. Presentation of BPC-157 may stimulate the growth hormone (GH) receptors, thereby inducing similar GH potential. BPC-157 peptide appears to bind with growth hormone receptors, possibly stimulating cell proliferation. This may lead to the development of new tissue composed of collagen and the development of a network of blood vessels in a process also called ‘angiogenesis.’ Consequently, the wound is ‘rebuilt’ and healed faster than the usual rate.(1) BPC-157 has also been studied in correlation to gastrointestinal function. Serotonin, an enteric neurotransmitter, is localized in the GI tract and GI mucosa. Altered serotonin levels may inhibit gastric acid secretion, affecting gut mucosal function and influencing gastric blood flow.(2) BPC-157 appears to have a particular antidepressant activity, which may counteract serotonin-induced action. The peptide may counteract the 5-HT2A receptors, restricting the serotonin binding with these receptors and thereby inhibiting its action.(3) The peptide has been researched for its potential action across diverse functions, including tissue repair, pain perception, gastrointestinal regulation, and tendon, ligament, muscle, and bone cell reparations. Multiple studies have since been conducted to understand the full action of the peptide, especially in the area of healing gastrointestinal ulceration, which is elaborated on below. Studies have suggested the peptide may increase the build-up of the blood vessels and induce anti-inflammation potential via improving functional recovery.(4) Chemical Makeup Molecular Formula: C62H98N16O22 Molecular Weight: 1419.55 g/mol Other Known Titles: Body Protection Compound-157 Research and Clinical Studies BPC-157 Peptide and Wound Healing In a study, three experimental murine models were used – first with skin tissue wounds, second with colon tissue anastomosis, and third with synthetic sponge implantation. A portion of the murine models were presented with a placebo, whereas others were presented with the BPC 157 peptide. After the study, all models were histologically examined. The researchers reported that the BPC-157 murine models appeared to exhibit higher numbers of collagen, reticulin, and blood vessel development than the ones in the control group.(5) In a particular study, researchers explored the theory that the peptide BPC-157 might potentially hasten wound healing compared to a control group. This hypothesis was rooted in observing possible improvements in several key areas of wound healing. These included the formation of new granulation tissue, which is critical in the healing process, along with reepithelialization. In this process, new epithelial cells form to replace those damaged by the wound. Additionally, there was an observation of potential improvements in dermal remodeling, a phase where the skin regains strength and elasticity, and collagen deposition, crucial for tissue repair.(6) The study also suggested that BPC-157 might have enhanced the expression of vascular endothelial growth factor (VEGF) in the injured skin tissues. VEGF is a significant protein that promotes blood vessel growth, vital to healing damaged tissues. The researchers further speculated that the peptide could have influenced umbilical vein endothelial cell proliferation (HUVECs). These cells line the blood vessels and are considered to be integral to forming new blood vessels during wound healing.(6) Additionally, there was a conjecture about a noticeable increase in the migration of HUVECs. This observation was based on results from wound healing assays, tests designed to measure various aspects of wound healing. The presence of BPC-157 might have led to an increased expression of VEGF-a, a variant of VEGF, and consequently accelerated the formation of vascular tubes in a laboratory setting. Moreover, the study hinted at the possibility that BPC-157 might influence the activity of specific proteins and enzymes involved in cellular signaling pathways. Specifically, it seemed that BPC-157 could regulate the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Phosphorylation is a process that activates or deactivates many protein enzymes and is a crucial step in sending signals within cells. The affected enzymes, ERK1/2, along with their downstream targets, including c-Fos, c-Jun, and Egr-1, are believed to play significant roles in cell growth, migration, and angiogenesis, which is the development of new blood vessels.(6) BPC-157 Peptide and Tendon Healing An experiment was conducted in the cultured tendon fibroblasts derived from the tendons of murine models. The cultures were divided into two groups; one was the control, whereas the other was presented with the peptide. Following the study, the following was reported:(1) The peptide appeared to promote the outgrowth of tendon fibroblasts and tissue healing; Even under H2O2 stress, BPC-157 appeared to stimulate apparent cell survival under stress; The peptide appeared to promote migration of the tendon fibroblasts; BPC-157 reportedly induced increased levels of phosphorylation of both PAK and paxillin, while the total protein level remained unchanged. Upon analysis, it was suggested that the peptide may impact tendon healing, tendon outgrowth, and cell survival via the F-actin formation and activation of the FAK and paxillin pathways.(1) F-actin formation is considered a key component in the cell's cytoskeleton, providing structure and aiding in cell movement. If BPC-157 enhances F-actin formation, this might indicate an improvement in the cytoskeletal organization and cell motility of tendon fibroblasts, which are essential for the repair and regeneration of tendon tissues. Further into the study, researchers utilized Western blotting, a laboratory method to detect specific proteins in a sample. Through this analysis, they suggested that BPC-157 might activate focal adhesion kinase (FAK) and paxillin, two proteins that play a significant role in cellular processes. The tentative finding was that the phosphorylation levels of FAK and paxillin appeared to increase in the presence of BPC-157. Interestingly, the total amounts of these proteins appeared to have remained unchanged, leading to the speculation that BPC-157's role might be more about activating existing molecules rather than increasing their production. This led to a further hypothesis that BPC-157 might activate the FAK-paxillin pathway. This pathway is considered to promote cell migration and adhesion, especially in tendon fibroblasts. The activation of this pathway could imply that BPC-157 plays a role in enhancing the movement and adherence of these cells, which are key processes in tendon healing and regeneration. BPC-157 Peptide and Gastrointestinal Healing A study was conducted to scrutinize the action of BPC-157 peptide against similar angiogenic growth factors such as EGF, FGF, and VEGF. The primary assumptions were that BPC-157 is highly stable, biocompatible, and sufficient to exert action when presented by itself. While the study reported improved healing, only BPC-157 appeared to have exhibited consistent results in all wound types (i.e., chronic and acute) on the esophagus, stomach, duodenum, and lower GI tract. This study suggested the extent of the angiogenic potential of the peptide is apparently very high as it appeared to extend not only on local wounds and ligaments but also on GI wounds and bone healing.(7) BPC-157 Peptide and Tissue Damage A study was conducted to understand the extent of the angiogenic potential of the peptide beyond local wounds, ligaments, and GI tract wounds and to study its action on multiple gastrointestinal lesions on the pancreas, liver injuries, heart damage, endothelium damage, and blood pressure. Following the results, scientists suggested that the BPC-157 peptide may induce a network of activities via peptidergic defense systems. There is also a possibility that BPC-157 may play a role in addressing both acute and chronic inflammation, aiding in wound healing, and assisting in the healing of fractures, including cases of pseudoarthrosis. This broad spectrum of potential suggests that BPC-157 could be part of the organism's unique peptidergic defense system.(8) There are several neurotransmitters and functions considered by scientists to be important, such as dopamine, nitrous oxide, prostaglandin, and other neuron systems. Any over-activity or inhibition of these systems may lead to lesions in different organs. BPC-157, through its defense system, appears to counteract these systems and possibly reverse their over-activation and inhibition. The researchers commented that these might include important systems, ”namely, dopamine-, NO-, prostaglandin-, somatosensory neuron-system,” and more.(8) BPC-157 Peptide and Muscle Healing A study was conducted on murine models with injured gastrocnemius muscle complex. These murine models were then presented with methylprednisolone (corticosteroid). These corticosteroid murine models were then divided into two groups: one was presented with BPC-157, and the other was presented with a placebo. Both compounds were presented once in 24 hours and examined on days 1, 2, 4, 7, and 14. Upon examination, it was reported that the corticosteroid appeared to significantly worsen the muscle damage in the murine models. However, BPC-157 appeared to exhibit apparent signs of healing and restoration of the damaged gastrocnemius muscle and restoring functioning ability.(9) Amphetamine-Induced Hypersensitivity Laboratory experiments have suggested that the BPC-157 peptide may have the ability to heal multiple different lesions – in the GI tract, liver, pancreas, and others. This trend in lab findings indicated that the peptide had some interaction with the dopamine system. To investigate further, this study presented the BPC-157 peptide in amphetamine (dopamine agonist) murine models. It was observed that BPC-157 appeared to be able to reverse the amphetamine-induced excitability in the murine models. Furthermore, murine models were presented with another dopamine agonist, haloperidol, and then presented with amphetamine on days 1, 2, 4, and 10. These murine models were then presented with BPC-157 to illustrate its action. Upon examination, it was suggested by the researchers that the peptide appeared to cause an almost complete reversal of the haloperidol action.(10) BPC-157 Peptide and Central Nervous System In a particular study using a murine model, researchers explored the potential of BPC-157 in the context of traumatic brain injury (TBI). BPC-157 might have played a role in significantly reducing the damage caused by TBI in experimental models, as indicated by improved early outcomes in the experiments conducted. During the critical 24-hour period following the injury, the observations hinted a minimal mortality rate in the BPC-157 group. Furthermore, the severity of traumatic lesions typically associated with TBI, such as subarachnoid hemorrhage (bleeding in the space between the brain and the tissues that cover it), intraventricular hemorrhage (bleeding inside the brain's ventricular system), brain laceration, and hemorrhagic laceration, appeared to be less pronounced in the murine models of the BPC-157 group. This suggested a protective potential of the peptide against such injuries.(11) Another interesting observation was the considerable improvement in brain edema, swelling in the brain tissue often caused by traumatic injuries. The hypothesis extended to the possibility that if BPC-157 were introduced before the occurrence of TBI, it might show an improved ratio of conscious/unconscious/death states in the test subjects. In other words, the peptide might potentially prevent or reduce the severity of unconsciousness and lower mortality rates associated with TBI in experimental models. Moreover, there was a suggestion that the immediate exposure of BPC-157 immediately before the injury may have mitigated the damage in the murine models subjected to a force impulse, typically used to simulate TBI in research. This hinted at the possibility of the peptide having preventive or protective potential against the immediate consequences of traumatic brain injury in experimental models.(11) BPC 157 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Chang, Chung-Hsun et al. “The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration.” Journal of applied physiology (Bethesda, Md. : 1985) vol. 110,3 (2011): 774-80. doi:10.1152/japplphysiol.00945.2010. https://pubmed.ncbi.nlm.nih.gov/21030672/ Ormsbee, H S 3rd, and J D Fondacaro. “Action of serotonin on the gastrointestinal tract.” Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) vol. 178,3 (1985): 333-8. doi:10.3181/00379727-178-42016. https://pubmed.ncbi.nlm.nih.gov/3919396/ Sikiric, Predrag et al. “Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications.” Current neuropharmacology vol. 14,8 (2016): 857-865. doi:10.2174/1570159x13666160502153022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333585/#r1 Krivic, A., Majerovic, M., Jelic, I. et al. Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone. Inflamm. res. 57, 205–210 (2008). https://doi.org/10.1007/s00011-007-7056-8 S Seiwerth, et al. “BPC 157's effect on healing.” Journal of physiology, Paris vol. 91,3-5 (1997): 173-8. doi:10.1016/s0928-4257(97)89480-6. https://pubmed.ncbi.nlm.nih.gov/9403790/ Huang, T., Zhang, K., Sun, L., Xue, X., Zhang, C., Shu, Z., Mu, N., Gu, J., Zhang, W., Wang, Y., Zhang, Y., & Zhang, W. (2015). Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro. Drug design, development and therapy, 9, 2485–2499. https://doi.org/10.2147/DDDT.S82030 Seiwerth, Sven et al. “BPC 157 and Standard Angiogenic Growth Factors. Gastrointestinal Tract Healing, Lessons from Tendon, Ligament, Muscle and Bone Healing.” Current pharmaceutical design vol. 24,18 (2018): 1972-1989. doi:10.2174/1381612824666180712110447. https://pubmed.ncbi.nlm.nih.gov/29998800/ Sikiric P. (1999). The pharmacological properties of the novel peptide BPC 157 (PL-10). Inflammopharmacology, 7(1), 1–14. https://doi.org/10.1007/s10787-999-0022-z https://pubmed.ncbi.nlm.nih.gov/17657443/ Pevec D, Novinscak T, Brcic L, Sipos K, Jukic I, Staresinic M, Mise S, Brcic I, Kolenc D, Klicek R, Banic T, Sever M, Kocijan A, Berkopic L, Radic B, Buljat G, Anic T, Zoricic I, Bojanic I, Seiwerth S, Sikiric P. Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application. Med Sci Monit. 2010 Mar;16(3):BR81-88. PMID: 20190676. https://pubmed.ncbi.nlm.nih.gov/20190676/ Jelovac, N et al. “A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by amphetamine and the development of haloperidol-induced supersensitivity to amphetamine.” Biological psychiatry vol. 43,7 (1998): 511-9. doi:10.1016/s0006-3223(97)00277-1. https://pubmed.ncbi.nlm.nih.gov/9547930/ Tudor, M., Jandric, I., Marovic, A., Gjurasin, M., Perovic, D., Radic, B., Blagaic, A. B., Kolenc, D., Brcic, L., Zarkovic, K., Seiwerth, S., & Sikiric, P. (2010). Traumatic brain injury in mice and pentadecapeptide BPC 157 effect. Regulatory peptides, 160(1-3), 26–32. https://doi.org/10.1016/j.regpep.2009.11.012 Gwyer, D., Wragg, N.M. & Wilson, S.L. Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing. Cell Tissue Res 377, 153–159 (2019). https://doi.org/10.1007/s00441-019-03016-8 Veljaca, Marija et al, The development of PL 14736 for treatment of inflammatory bowel disease, Advanced in GI pharmacology, 2002 O-32. https://www.bib.irb.hr/192824 Phase I clinical trial in healthy volunteers to study safety and pharmacokinetics of BPC-157, a pentadecapeptide from gastric source. https://clinicaltrials.gov/ct2/show/NCT02637284? Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Fragment 176-191 & Mod GRF 1-29 & Ipamorelin Blend (12mg)
Modified GRF 1-29 is a truncated version of Growth Hormone-Releasing Hormone (GHRH). Unlike GHRH, Mod GRF 1-29 is not a full-length peptide but rather a shorter version containing only 29 amino acids. In Mod GRF 1-29, four of the original amino acids have been modified, to enhance its stability. These modifications serve to make the molecule more resistant to degradation by dipeptidyl peptidase-4 (DPP-4) enzymes, which would otherwise break down the peptide structure. By reducing susceptibility to enzymatic degradation, these modifications may potentially increase the peptide's half-life and improve its pharmacokinetics.(1) Ipamorelin is a synthetic pentapeptide, falling under the growth hormone secretagogue receptor (GHSR) agonist category. The peptide was derived from GHRP-1, which in turn is an analog of met-enkephalin, but potentially may not possess affinity to the opioid receptors. It appears to activate the ghrelin receptors (GHSR) which appear to trigger growth hormone synthesis. Fragment 176-191, as the name implies, is a small ‘fragment’ of the growth hormone (hGH), also referred to as the “fat-burning peptide” for its potential in that area.(2) Fragment 176-191 peptide, composed of 16 amino acids, including the last 15 amino acids from 177 to 191 found in hGH, has tyrosine added at the N-terminus (beginning). The peptide is also known as AOD 9604.(3) Chemical Makeup(1)(3)(4) Molecular formula Fragment 176-191: C78H125N23O23S2 Modified GRF 1-29: C152H252N44O42 Ipamorelin: C38H49N9O5 Molecular weight Fragment 176-191: 1817.12 g/mol Modified GRF 1-29: 3367.9 g/mol Ipamorelin: 711.8 g/mol Other known titles Modified GRF 1-29: Mod GRF 1-29, CJC-1295 without DAC Ipamorelin Ipamorelin Acetate, IPA Fragment 176-191: AOD 9604, GH (hGH) lipolytic fragment, Somatostatin (177-191), tyrosyl Research and Clinical Studies Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and Lipolytic Action The peptide in the blend that is believed to possess the most potent lipolytic (fat-breaking) action is likely Fragment 176-191. In one study,(2) obese experimental murine models were subjected to the peptide for two consecutive weeks. After the completion of the study, it was noted that there appeared to be a significant reduction in the body weight of these murine models, including a reduction of excess body lipids. These results were deemed correlated to the increased concentration of the lipolytic ß3-AR receptors, indicating the peptides may work via the beta-adrenergic pathway. Further studies were conducted on the experimental mice with knocked-out lipolytic receptors. The peptide mice were reported to have experienced considerable weight loss, suggesting that the peptide may not depend on the lipolytic receptors to exert any action. Instead, it may possibly produce some fat-burning action via energy expenditure and fat oxidation. As per M Heffernan and his team, “this study demonstrates that the lipolytic actions of both hGH and AOD9604 are not mediated directly through the beta(3)-AR although both compounds increase beta(3)-AR expression, which may subsequently contribute to enhanced lipolytic sensitivity.” (2) Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and the Pituitary Gland One review of the available literature(5) suggested that these peptides appeared to yield various physiological changes, including “increase lean body mass, reduce fat mass, increase exercise tolerance and maximum oxygen uptake, enhance muscle strength, and improve linear growth…” in obese test models.(5) While Fragment 176-191 was suggested to exert its potential action for weight loss via peripheral mechanisms, the aforementioned observation in the review are related to the apparent central action of peptides like Mod GRF 1-29 and Ipamorelin on the pituitary gland. For example, Ipamorelin appears to work by potentially binding to the GHS-R1a receptor, also known as the growth hormone secretagogue receptor type 1a, which is found in the pituitary gland and the hypothalamus. Upon binding, this receptor activation may trigger a series of intracellular events that potentially culminate in the release of stored growth hormone from somatotroph cells (GH-producing cells) in the anterior pituitary. The apparent activation of the GHS-R1a receptor by Ipamorelin may lead to increased intracellular calcium ions through the phospholipase C pathway. The elevated calcium levels may prompt the secretory vesicles inside somatotropic cells to release growth hormone. On the other hand, Mod GRF 1-29 appears to interact with the GHRH receptors on somatotrophs in the anterior pituitary gland. Upon binding to the GHRH receptors, Mod GRF 1-29 appears to instigate a cascade of intracellular signaling events. One of the key pathways activated appears to be the adenylyl cyclase pathway. Activation of this pathway may result in the conversion of ATP (adenosine triphosphate) into cAMP (cyclic adenosine monophosphate). This rise in cAMP appears to activate protein kinase A (PKA), which then may lead to the phosphorylation of various proteins, including voltage-dependent calcium channels on the cell membrane. The subsequent opening of these calcium channels potentially facilitates the influx of calcium ions into the somatotropic cells. Elevated intracellular calcium concentrations, in turn, appear to prompt the secretory vesicles inside these cells to release growth hormone into the bloodstream. It is posited that through this series of intracellular events that Mod GRF 1-29, upon binding to GHRH receptors, the peptide might facilitate the release and synthesis of growth hormone. The combination of Mod GRF 1-29 with certain growth hormone-releasing peptides like Ipamorelin, may potentially lead to a synergistic action, apparently amplifying the release of growth hormone. Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and Fat Burning In 2004, a clinical trial(6) was launched, consisting of 300 obese test subjects. All these subjects were presented with the Fragment 176-191 peptide for 12 consecutive weeks. All subjects were divided into 6 groups – one group was presented with saline placebo, and the rest were given different peptide concentrations. After 12 weeks, when the subjects were examined, the group presented with the minor concentration appeared to exhibit the highest reduction in subject body weight (up to an average of 2.8 kilograms). Moreover, the trial also suggested that the peptide may have helped to improve these candidates’ cholesterol profiles and glucose tolerance levels. As per Chris Belyea, “The evidence from the trial is that over 12 weeks AOD9604 induces competitive weight loss with accompanying health benefits at a low dose and has superior tolerability.” (6) Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and Regeneration In one 2015 study,(7) 32 experimental rabbits were enrolled and divided into four groups of eight. All four groups were presented with placebo, Fragment 176-191 peptide, hyaluronic acid, or a combination of the peptide and hyaluronic acid. This study was conducted for approximately 7 weeks. After the completion of the study, all rabbits were examined for cartilage damage. Among all groups, the rabbits presented with the peptide and hyaluronic acid combination appeared to exhibit minor cartilage degeneration. The report concluded that “Intra-articular AOD9604 [administration] using ultrasound guidance enhanced cartilage regeneration, and combined AOD9604 and HA [administration] were more effective than HA or AOD9604 [doses] alone in the collagenase-induced knee OA rabbit model.” (7) Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend and Bone Mineralization Considering the different peptides in the blend, Ipamorelin appears to be the one with a potential for improving bone mass and mineralization in experimental models. Preliminary experiments on murine models suggest that Ipamorelin may have mitigated the loss of muscle strength, which can occur in artificially-induced catabolic conditions.(8) The researchers also commented that introduction of the peptide appeared to have increased bone mineralization in the murine models subjected to a combination of Ipamorelin and catabolism-inducing agents, in contrast to the control group receiving only catabolism-inducing agents. Other trials on experimental murine models also suggest that Ipamorelin may elevate bone mineral content, pointing toward denser and more robust bone formation.(9) The researchers utilized dual X-ray absorptiometry (DEXA) to observe the potential impact of Ipamorelin on bone mineral density in real-time, focusing on areas like the femur and L6 vertebrae. Post-research, the femurs of the murine subjects were analyzed using mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. The DEXA observations hint at a possible increase in tibial and vertebral BMC (bone mineral content) due to the peptide, differing from the control group. Additionally, the pQCT findings imply that the enhanced cortical BMC might stem from an expanded cross-sectional bone area, suggesting that the femur and L6 vertebrae could have seen heightened bone mineralization. Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend and Appetite Ipamorelin appears to activate the ghrelin receptors in the pituitary (GHSR1a) but may also trigger the receptors for ghrelin in other systems. Considering its potential impact on ghrelin receptors, Ipamorelin may enhance appetite, possibly leading to weight gain. Research indicates that Ipamorelin might have contributed to an approximate 15% increase in the body weight of murine models.(10) Some theories suggest that Ipamorelin may have proportionally increased fat pad weights relative to total body weight, resulting in a noticeable rise in body fat, as detected by DEXA. Additionally, there are hints that Ipamorelin may have boosted serum leptin levels, a hormone associated with energy and appetite control. As a result, researchers theorize that murine models in the Ipamorelin groups could have consumed more food, leading to the observed weight gain. Fragment 176-191 & Modified GRF 1-29 & Ipamorelin peptide blend is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 91976842, CJC1295 Without DAC. https://pubchem.ncbi.nlm.nih.gov/compound/CJC1295-Without-DAC. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001 Dec;142(12):5182-9. doi: 10.1210/endo.142.12.8522. PMID: 11713213. https://pubmed.ncbi.nlm.nih.gov/11713213/ National Center for Biotechnology Information (2023). PubChem Substance Record for SID 319360420, 386264-39-7, Source: ToxPlanet. https://pubchem.ncbi.nlm.nih.gov/substance/319360420 National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 9831659, Ipamorelin. https://pubchem.ncbi.nlm.nih.gov/compound/Ipamorelin. Sigalos, John T, and Alexander W Pastuszak. “The Safety and Efficacy of Growth Hormone Secretagogues.” Sexual medicine reviews vol. 6,1 (2018): 45-53. doi:10.1016/j.sxmr.2017.02.004 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632578/ News, Medical and Life Sciences, Obesity drug codenamed AOD 9604 highly successful in trials, 16 December 2004, https://www.news-medical.net/news/2004/12/16/6878.aspx. Kwon DR, Park GY. Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Ann Clin Lab Sci. 2015 Summer;45(4):426-32. PMID: 26275694. https://pubmed.ncbi.nlm.nih.gov/26275694/ Andersen, N. B., Malmlöf, K., Johansen, P. B., Andreassen, T. T., Ørtoft, G., & Oxlund, H. (2001). The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 11(5), 266–272. https://doi.org/10.1054/ghir.2001.0239 Svensson, J., Lall, S., Dickson, S. L., Bengtsson, B. A., Rømer, J., Ahnfelt-Rønne, I., Ohlsson, C., & Jansson, J. O. (2000). The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. The Journal of endocrinology, 165(3), 569–577. https://doi.org/10.1677/joe.0.1650569 Lall, S., Tung, L. Y., Ohlsson, C., Jansson, J. O., & Dickson, S. L. (2001). Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues. Biochemical and biophysical research communications, 280(1), 132–138. https://doi.org/10.1006/bbrc.2000.4065 Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Follistatin-344 (1mg)
Follistatin-344 is a naturally occurring glycoprotein that is considered to be present in almost all tissues. It is considered an autocrine chemical, meaning that the cell produces a chemical messenger through a cell signal, which binds to its autocrine receptors, resulting in cell modification.(1) Follistatin naturally occurs in two isoforms, FST 317 and FST 344, each containing 288 and 315 amino acids, respectively. These two isoforms may be produced through an alternative splicing process of the mRNA.(2) Their names are based on the parent molecules from which they are derived and contain 317 and 344 amino acids, respectively. Follistatin-344 is considered to be the predominantly expressed molecule in most tissues, while the Follistatin-317 isoform may account for less than 5% of the encoded mRNA. Follistatin-344 is a synthetic version of the endogenous Follistatin-344 protein isoform. Although the number of amino acids differs in Follistatin isoforms, at its core, the protein comprises 63 amino acid residues and three domains: FSD1, FSD2, and FSD3, with an identical structure in the synthetic peptide.(3) These domains comprise 73-77 amino acid residues and are characterized by 10 conserved cysteine residues. Overview Researchers posit that Follistatin's primary potential may exist in activin-binding action.(4) Follistatin has been suggested to have a collaborative role in reproductive functioning alongside other chemicals like activin and inhibins. Scientists posit that the ovarian follicle mainly releases activin to enhance the secretion of follicle-stimulating hormone. Follistatin may bind with activin and attenuate its action by inhibiting the secretion of the FSH hormone. While the origin and mechanism of the peptide hormone are not entirely understood, it has been suggested that Follistatin-344 is locally produced in the pituitary gland, gonads, testes, and ovaries. Additionally, Follistatin may be vastly distributed in various organs and potentially may be present in blood circulation due to its secretion from the blood vessels. Further, Follistatin-344 is hypothesized to interact with various proteins within the Transforming Growth Factor-beta (TGFβ) superfamily.(16) This superfamily includes several key regulatory proteins in cellular growth and differentiation. One potential interaction is with the Bone Morphogenetic Proteins (BMPs), which are believed to play roles in bone formation, embryonic development, and cellular growth. It is conjectured that Follistatin-344 might modulate the activity of certain BMPs, though the specific proteins and mechanisms remain uncertain and require further exploration. Another possible interaction involves Growth Differentiation Factor 9 (GDF9), crucial for ovarian follicle development in female organisms. The binding of Follistatin-344 to GDF9 may suggest a regulatory role in reproductive processes, but this interaction is not fully understood and is subject to ongoing research. However, the most notable of these interactions is with Growth Differentiation Factor 8 (GDF8), commonly known as myostatin. Myostatin is deemed integral to controlling muscle cell growth and differentiation, acting as a natural inhibitor to prevent excessive muscle development. It is proposed that Follistatin-344 binds to myostatin, potentially inhibiting its function. This inhibition may theoretically facilitate an increase in muscle mass by allowing muscle cells greater freedom to grow and differentiate. The potential for Follistatin-344 to enhance muscle growth through myostatin inhibition presents a significant area of interest, although the actual outcomes may vary and are highly dependent on singular biological conditions. Chemical Makeup Molecular Formula: N/A Molecular Weight: 3780 g/mol Other Known Titles: Activin-Binding Protein, FSH-Suppressing Protein, FST Research and Clinical Studies Follistatin-344 and Muscle Development Myostatin is a protein considered to be synthesized by muscle cells, hindering muscle cell differentiation and growth. As mentioned, myostatin protein belongs to the transforming growth factor-beta (TGF-beta) protein, which Follistatin may inhibit. During one 1997 study,(5) it was suggested that mice given Follistatin-344 exhibited reduced levels of myostatin, which might have led to the improved skeletal muscle mass with each mouse weighing 2 to 3 times more than usual, and the increase in mass appeared to result from a combination of muscle cell hyperplasia and hypertrophy. In another study,(6) Follistatin-344 was induced in mice via a nanoparticle-mediated mode of delivery of mRNA in the liver. The researchers reported that the mRNA messenger appeared to stimulate the hepatic liver cells to naturally synthesize and secrete Follistatin. Results of this study suggested that the peptide mice, given this mRNA-containing nanoparticle, exhibited apparently increased serum levels of Follistatin within three days as compared to the levels in control mice. The research posits that Follistatin mRNA is translated in the liver, leading to increased serum levels of Follistatin. This elevation in Follistatin was suggested to persist for up to 72 hours post-presentation and was associated with decreased serum concentrations of myostatin and activin A. Activin A is a protein considered to be involved in a myriad of biological processes. It is a member of the transforming growth factor-beta (TGF-β) superfamily. It appears to play significant roles in regulating various cellular functions such as proliferation, differentiation, and apoptosis in numerous cell types. In the context of muscle physiology, activin A is particularly noteworthy for its role in muscle metabolism and remodeling. It is thought to be a critical regulator of muscle mass, as it appears to negatively influence muscle growth by promoting catabolic pathways that lead to muscle atrophy. This action is mediated primarily through its interaction with the activin type IIB receptor (ActRIIB) on muscle cells. Upon binding to this receptor, activin A activates intracellular signaling pathways that increase muscle protein breakdown and inhibit muscle protein synthesis. After 8 weeks of continuous peptide presentation, the lean muscle mass of the peptide mice was reportedly 10% more than the control mice. In contrast to experiments targeting myostatin—such as anti-myostatin antibodies—Follistatin offers a broader research approach by also antagonizing activin A. Myostatin-specific experiments primarily focus on inhibiting pathways that directly limit muscle growth, thus promoting hypertrophy. However, they might not address other pathways that contribute to muscle loss, such as fibrosis or inflammation, which are influenced by activin A. Follistatin’s dual antagonistic action might lead to more comprehensive impact in muscle dystrophy models. By inhibiting both myostatin and activin A, Follistatin may not only enhance muscle mass but also reduce muscle stiffness and weakness associated with fibrotic changes. This potential dual action is particularly advantageous because it may address both the loss of muscle mass and the quality of the remaining muscle tissue, potentially leading to improvements in muscle function and strength that surpass those achieved by solely blocking myostatin.(7) Follistatin-344 and Carcinogenic Cells Breast Cancer Cells Through reverse transcription polymerase chain reaction study (RT-PCR), researchers suggested that Follistatin levels may fluctuate in animal models of breast cancer.(8) One study(9) examined the available gene expression data of mice with breast cancer. In most cases, Follistatin was reportedly under-expressed in carcinogenic breast cells, possibly leading to the increased spread of cancer cells caused by activin proteins. As Follistatin is suggested to bind to and inhibit activin proteins, it was further posited by the researchers that restoring Follistatin in these mice might prevent the prognosis of activin-induced metastasis and improve overall survival. Esophageal Cancer Cells Research suggests that bone morphogenic protein (BMP) is one of the causative factors in the transition of normal esophageal tissue to cancerous tissues. Follistatin, speculated to host the capacity to bind and neutralize activin and myostatin, may also interact with BMPs. By modulating the activity of BMP, Follistatin may serve a protective role against the over-proliferation of cellular pathways often seen in cancerous tissues. Experimental studies in Follistatin-344 suggest that the peptide may counteract acid reflux actions, thereby possibly preventing an over-activation of BMP and the development of esophageal cancer cells. More specifically, Follistatin's potential to inhibit BMP might theoretically prevent the initial steps required for the transformation of normal tissue into cancerous tissue, particularly in environments exacerbated by chronic inflammation or external insults like acid reflux.(10) Follistatin-344 and Cell Proliferation There is an odd contrast in the working of Follistatin: it may potentially inhibit metastasis, as well as possibly promote cell proliferation. This is why the peptide is researched in studies scrutinizing increased tumor growth (tumorigenesis) and metastasis.(12) Research has suggested that hepatocytes (i.e., liver cells) may require Follistatin to proliferate. When studied in experimental rats, it was reported by the researchers that the inactivation of activin by Follistatin-344 may be a precondition for cell proliferation to occur. They believed there might be some energy exchange amongst the cells where the energy used for cell migration is shut off to switch with cellular growth and proliferation. Follistatin-344 and Liver Protection One study(13) was conducted to determine the potential of Follistatin on early liver fibrosis. In this study, rats were divided into one control group and one Follistatin-exposed group for a period of four weeks. Researchers reported that the peptide group showed a 32% decrease in liver fibrosis compared to the control group. They further reported that hepatocytic apoptosis was decreased by almost 90% in the Follistatin mice. Follistatin-344 and Follicle Growth Follistatin may exhibit wound healing potential via possible stimulation of interfollicular stem cells, which may lead to increased hair growth. A clinical study was conducted where the potential of this synthetic protein formulation, Hair Stimulating Complex (HSC), was studied in subjects with hair loss.(14) A cohort of 26 subjects were presented with the peptide for a period of 52 weeks. Histopathological evaluation of the tissues reportedly showed improved hair growth after 52 weeks compared to the control group. Besides hair growth, researchers reported an apparent improvement in hair thickness and density by almost 13%. Follistatin-344 and Diabetic Mice Models Researchers suggested that when Follistatin-344 was presented to diabetic murine models, it appeared to lead to overexpression of the protein in the pancreatic cells, resulting in increased pancreatic beta cell (β-cell) mass, reduced glucose level, and overall reduction in diabetic symptoms.(15) β-cells are a population of cells in the pancreas primarily tasked with producing insulin to lower glucose levels. The data suggest that this β-cell proliferation is possibly due to the inhibition of SMAD2/3 signaling, a pathway typically activated by transforming growth factor-beta (TGF-β) superfamily members such as activin and myostatin, which are believed to be antagonized by Follistatin. This inhibition might indirectly activate the insulin-phosphoinositide 3-kinase (PI3K)-Akt pathway, posited as crucial for cell growth and survival, potentially contributing to increased β-cell mass and improved glucose homeostasis. The researcher’s comments suggest that β-cell specific overexpression of Follistatin may lead to several notable outcomes in the tested db/db mice: a substantial increase in pancreatic islet mass, enhanced β-cell proliferation indicated by co-immunofluorescent staining for Ki67 and insulin, and improved overall metabolic profiles including reduced hyperglycemia. It is also noted that these actions were accompanied by changes in insulin signaling within the pancreas, as detailed by elevated insulin levels and enhanced activation of the insulin-PI3K-Akt signaling pathway. Moreover, the study posits that Follistatin may influence the expression of other regulatory proteins and genes within the pancreas. For instance, the increased mRNA levels of myostatin and activin, along with their inhibitors BAMBI and inhibin-α, suggest a complex interplay where Follistatin may act to modulate these signaling molecules, possibly leading to an enhanced β-cell proliferative environment. Additionally, the study explores the potential modulation of betatrophin, a hormone implicated in β-cell proliferation. The researchers observed a significant increase in betatrophin expression in the Follistatin groups, which might be facilitated by the suppressed activity of activin and myostatin due to Follistatin action. This suggests that Follistatin may be enhancing β-cell proliferation not only through direct inhibition of negative growth regulators but also by promoting positive growth signals such as betatrophin. Follistatin-344 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Hiroyuki Kaneko, Handbook of Hormones, 2016. FST follistatin [Homo sapiens (human)]. https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=DetailsSearch&Term=10468 Shi, L., Resaul, J., Owen, S., Ye, L., & Jiang, W. G. (2016). Clinical and Therapeutic Implications of Follistatin in Solid Tumours. Cancer genomics & proteomics, 13(6), 425–435. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219916/ Rodino-Klapac, L. R., Haidet, A. M., Kota, J., Handy, C., Kaspar, B. K., & Mendell, J. R. (2009). Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle & nerve, 39(3), 283–296. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717722/ McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997 May 1;387(6628):83-90. https://pubmed.ncbi.nlm.nih.gov/9139826/ Schumann C, Nguyen DX, Norgard M, Bortnyak Y, Korzun T, Chan S, Lorenz AS, Moses AS, Albarqi HA, Wong L, Michaelis K, Zhu X, Alani AWG, Taratula OR, Krasnow S, Marks DL, Taratula O. Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA. Theranostics 2018; 8(19):5276-5288. doi:10.7150/thno.27847. https://www.thno.org/v08p5276.htm Iskenderian A, Liu N, Deng Q, Huang Y, Shen C, Palmieri K, Crooker R, Lundberg D, Kastrapeli N, Pescatore B, Romashko A, Dumas J, Comeau R, Norton A, Pan J, Rong H, Derakhchan K, Ehmann DE. Myostatin and activin blockade by engineered follistatin results in hypertrophy and improves dystrophic pathology in mdx mouse more than myostatin blockade alone. Skelet Muscle. 2018 Oct 27;8(1):34. https://pubmed.ncbi.nlm.nih.gov/30368252/ Zabkiewicz C, Resaul J, Hargest R, Jiang WG, Ye L. Increased Expression of Follistatin in Breast Cancer Reduces Invasiveness and Clinically Correlates with Better Survival. Cancer Genomics Proteomics. 2017 Jul-Aug;14(4):241-251. https://pubmed.ncbi.nlm.nih.gov/28647698/ Seachrist DD, Sizemore ST, Johnson E, Abdul-Karim FW, Weber Bonk KL, Keri RA. Follistatin is a metastasis suppressor in a mouse model of HER2-positive breast cancer. Breast Cancer Res. 2017 Jun 5;19(1):66. target="_blank" rel="noopener"https://pubmed.ncbi.nlm.nih.gov/28583174/ Lau MC, Ng KY, Wong TL, Tong M, Lee TK, Ming XY, Law S, Lee NP, Cheung AL, Qin YR, Chan KW, Ning W, Guan XY, Ma S. FSTL1 Promotes Metastasis and Chemoresistance in Esophageal Squamous Cell Carcinoma through NFκB-BMP Signaling Cross-talk. Cancer Res. 2017 Nov 1. https://pubmed.ncbi.nlm.nih.gov/28883005/ Shi L, Resaul J, Owen S, Ye L, Jiang WG. Clinical and Therapeutic Implications of Follistatin in Solid Tumours. Cancer Genomics Proteomics. 2016 11-12;13(6):425-435. https://pubmed.ncbi.nlm.nih.gov/27807065/ Ooe H, Chen Q, Kon J, Sasaki K, Miyoshi H, Ichinohe N, Tanimizu N, Mitaka T. Proliferation of rat small hepatocytes requires follistatin expression. J Cell Physiol. 2012 Jun;227(6):2363-70. https://pubmed.ncbi.nlm.nih.gov/21826650/ Patella S, Phillips DJ, Tchongue J, de Kretser DM, Sievert W. Follistatin attenuates early liver fibrosis: effects on hepatic stellate cell activation and hepatocyte apoptosis. Am J Physiol Gastrointest Liver Physiol. 2006 Jan;290(1):G137-44. https://pubmed.ncbi.nlm.nih.gov/16123203/ Zimber MP, Ziering C, Zeigler F, Hubka M, Mansbridge JN, Baumgartner M, Hubka K, Kellar R, Perez-Meza D, Sadick N, Naughton GK. Hair regrowth following a Wnt- and follistatin containing treatment: safety and efficacy in a first-in-man phase 1 clinical trial. J Drugs Dermatol. 2011 Nov;10(11):1308-12. https://pubmed.ncbi.nlm.nih.gov/22052313/ Zhao C, Qiao C, Tang RH, Jiang J, Li J, Martin CB, Bulaklak K, Li J, Wang DW, Xiao X. Overcoming Insulin Insufficiency by Forced Follistatin Expression in β-cells of db/db Mice. Mol Ther. 2015 May;23(5):866-874. doi: 10.1038/mt.2015.29. Epub 2015 Feb 13. PMID: 25676679; PMCID: PMC4427879. https://pubmed.ncbi.nlm.nih.gov/25676679/ Reichel C, Gmeiner G, Thevis M. Detection of black market follistatin 344. Drug Test Anal. 2019 Nov;11(11-12):1675-1697. doi: 10.1002/dta.2741. Erratum in: Drug Test Anal. 2020 Oct;12(10):1522-1533. PMID: 31758732. Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
B7-33 (6mg)
H2-relaxin is a naturally occurring, endogenous protein compound, which was synthetically mimicked and named the “B7-33” peptide. The H2-relaxin protein class comprises relaxin, H3-relaxin, insulin-like peptide-3, and insulin-like peptide-5. All these proteins have been suggested to exhibit a variety of biological actions, including possibly affecting genetic functions and the reproductive, musculoskeletal, and cardiovascular systems.(2) Considered structurally similar to H2-relaxin, the synthetic equivalent B7-33 may possess anti-fibrotic potential. There are four different receptors that these naturally produced relaxin proteins are speculated to bind with, namely RXFP-1, RXFP-2, RXFP-3, and RXFP-4. Each receptor has a different action, as outlined below:(2) RXFP-1 receptor is suggested to influence sperm motility RXFP-2 receptor appears to impact testicular development RXFP-3 receptor may play a role in circadian rhythm and sleep cycle regulation RXFP-4 receptor has shown indications of affecting hunger hormone signaling cycles Due to the variety of receptors involved and a wide range of biological impact, extensive research has been conducted on the relaxin protein and its analogs, such as the B7-33 peptide, to fully understand their potential. Overview B7-33 is a singular chain peptide, a smaller analogous derivative of the endogenous relaxin protein.(3) Typically, the relaxin peptide comprises four components - a signal peptide, B chain, C chain, and COOH terminal. Several studies were conducted initially to replicate these peptide structures, however the researchers reported that results indicated it being highly insoluble and inactive. After extensive subsequent research, scientists modified the structure by producing a B chain and elongating the COOH terminal, thereby forming the first-ever soluble analog - B7-33 peptide - in 2016.(3) Besides the structural difference, the peptide has other variations from the endogenous protein. B7-33 peptide has been suggested to act via the pERK pathway instead of the cAMP pathway. The pERK pathway is a signaling route within cells that may affect cell function, often related to cell growth and survival. In contrast, the cAMP pathway involves different cellular activities primarily related to energy balance and metabolism. H2-relaxin has been suggested to produce antifibrotic potential via the cAMP pathway, which may stimulate tumor formation.(1) Furthermore, the peptide may have a strong affinity towards the RXFP-1 receptors. The peptide appears to bind with these RXFP-1 receptors, stimulating the pERK pathway, which then may lead to increased synthesis of MMP-2 matrix metalloproteinase chemicals. MMP-2 is an enzyme that breaks down proteins and plays a crucial role in tissue remodeling and repair. These chemicals then possibly inhibit the scarring of tissues, thereby preventing fibrosis.(1) Fibrosis is considered the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process, which is associated with a loss of function. Chemical Makeup Molecular Formula: C131H228N40O37S Molecular Weight:2987,75 g/mol Other Known Titles: (B7-33)H2, GTPL9321 Research and Clinical Studies B7-33 Peptide and Vasoprotection This 2017 study(4) was conducted on male Wistar murine models where their tails were presented with a control compound (which was sodium acetate), H2 relaxin, or B7-33 peptide. After three hours, these mice were examined for their vascular functions, mainly in the mesenteric artery, renal artery, and abdominal aorta. While the results were not as promising in the renal artery and abdominal aorta, B7-33 and H2 relaxin exhibited potential vasodilatory properties in the mesenteric artery. Thus, the results suggest that both B7-33 and serelaxin may preferentially augment bradykinin-induced endothelium-dependent relaxation, particularly emphasizing the mesenteric artery in rats. This augmentation appears to be linked to enhanced endothelium-derived hyperpolarization. To understand better, the researchers reported an additional study(4) carried out in female murine models experimentally induced with endothelial dysfunction. These mice were then either given B7-33 or H2 relaxin. Following the study, the researchers suggested that both compounds may have helped combat and prevent the further spread of endothelial dysfunction in mice. These results suggest that B7-33 has the potential to replicate the vasoprotective action of H2 relaxin and thereby protect blood vessels from further damage. B7-33 Peptide and Preeclampsia Preeclampsia is a pregnancy ailment characterized by increased hypertension in mothers and decreased fetal weight. This clinical study(5) was conducted to understand the potential of B7-33 peptide in pregnant females with preeclampsia. A cell culture of cytotrophoblasts (CTBs) was used. Cytotrophoblasts are the cells found in the inner cellular layer of the embryo. These cells were given either control compound, a marinobufagenin steroid, or glucose for two days. Following this preparation, some of these cells were given either a relaxin antagonist, or the B7-33 compound. Upon examination, the cells given B7-33 peptide appeared to exhibit an upregulation of the vascular endothelial growth factor, VEGF. Cells that were given relaxin antagonists exhibited apparent reduced VEGF concentration. VEGF is thought to stimulate the proliferation and migration of endothelial cells, which line the interior surfaces of blood vessels. By potentially enhancing these processes, VEGF may play a vital role in forming new vascular structures, essential for supplying tissues with oxygen and nutrients, especially during rapid growth or healing periods. VEGF's actions are primarily mediated through two tyrosine kinase receptors, VEGFR-1 and VEGFR-2, located on the surface of endothelial cells. The binding of VEGF to these receptors is thought to trigger a cascade of signaling pathways that could lead to endothelial cell proliferation, migration, and survival. B7-33 Peptide and Anti-Fibrosis Studies(6)(7) have suggested that when presented with a fully extended strain of H2 relaxin protein, it may induce an increased heart rate and possibly stimulate the spread of carcinogenic cells. This is mainly attributed to its mechanism as it appears to activate the cAMP pathway. Hence, researchers are looking for a derivative that might produce the exact biological action of anti-fibrosis without cAMP activation. When the peptide was exposed in mice with myocardial infarction, it was reported to result in almost 50% reduction in cardiac tissue fibrosis. Furthermore, a study(1) was also conducted in mice with prostate diseases. These mice were presented with two different concentrations of B7-33 peptide. At both concentrations, the results were the same, and researchers suggested that the compound might contribute to the development of fibrosis without promoting the spread of prostate tumors. This suggested that the peptide may have the potential to act via the pERK pathway and not via cAMP activation. The designation "pERK" refers to the phosphorylated state of extracellular signal-regulated kinase (ERK), indicating its activated status. It is hypothesized that the activation pathway initiates when a growth factor interacts with its corresponding receptor on the cellular surface, potentially activating the receptor's intrinsic kinase capabilities. This interaction is believed to initiate a sequence of phosphorylation events, transmitting the signal through a network of intermediary proteins, such as RAF and MEK (MAPK/ERK kinase). This sequence is thought to ultimately result in the phosphorylation and subsequent activation of ERK. Following activation, it is suggested that ERK translocates to the nucleus where it may phosphorylate various transcription factors, potentially leading to changes in gene expression that might influence cellular processes, including division and differentiation. B7-33 Peptide as a Coating Material In one animal study(8), a peptide-coated device was implanted in murine models. The researchers were curious to see if the peptide might counteract possible fibrotic actions in the mice. As a result of this peptide release from the device coating, the reduction in device thickness (by fibrosis) was reported to be decreased by 49.2% over the 6-week duration of the study. B7-33 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Mohammed Akhter Hossain et al, A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1, Drug Discovery Biology Pharmacology Monash Biomedicine Discovery Institute, Vol 7, 2016. R J Summers, Recent progress in the understanding of relaxin family peptides and their receptors, British Journal of Pharmacology, Vol 174, issue 10, pg 915-920. https://doi.org/10.1111/bph.13778 Nitin A Patil et al, Relaxin family peptides: structure–activity relationship studies, British Pharmacological Society, vol 174 issue 10, published 06 December 2016. https://doi.org/10.1111/bph.13684 Marshall SA, O'Sullivan K, Ng HH, Bathgate RAD, Parry LJ, Hossain MA, Leo CH. B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin). Eur J Pharmacol. 2017 Jul 15;807:190-197. doi: 10.1016/j.ejphar.2017.05.005. Epub 2017 May 3. PMID: 28478069. https://pubmed.ncbi.nlm.nih.gov/28478069/ S.H Afroze et al, Abstract P3042: Novel Peptide B7-33 and It's Lipidated Derivative Protect Cytotrophoblasts From Preeclampsia Phenotype in a Cellular Model of the Syndrome, 4 Sep 2019. https://doi.org/10.1161/hyp.74.suppl_1.P3042 Silvertown JD, Ng J, Sato T, Summerlee AJ, Medin JA. H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis. Int J Cancer. 2006 Jan 1;118(1):62-73. https://pubmed.ncbi.nlm.nih.gov/16049981 Shu Feng, Irina U. Agoulnik, Natalia V. Bogatcheva, Aparna A. Kamat, Bernard Kwabi-Addo, Rile Li, Gustavo Ayala, Michael M. Ittmann and Alexander I. Agoulnik, Relaxin Promotes Prostate Cancer Progression, March 2007. https://clincancerres.aacrjournals.org/content/13/6/1695 N.Welch et al, Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic Encapsulation, ACS Applied Materials and Interfaces, Nov 2019. www.researchgate.net/publication/337205944_Coatings_Releasing_the_Relaxin_Peptide_Analogue_B7-33_Reduce_Fibrotic_Encapsulation Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Humanin (10mg)
Humanin is a short natural peptide with suggested potential in cell metabolism and inflammation response.(3) Researchers have suggested that a mitochondrial genome called ‘16S ribosomal RNA gene’ encodes the Humanin peptide.(4) Researchers further posit that the peptide's length may depend on the location of its synthesis. The peptide may contain 21 amino acids if synthesized inside the mitochondria, whereas it may contain 24 amino acids if synthesized outside the mitochondria but inside the cytosol.(5) Both of these peptides exhibit potential biological activity. Mitochondria are considered the powerhouses of the cell, and are formed from the engulfment of individual prokaryotes. Eventually, the eukaryotes appear to engulf the prokaryotic (single-celled) organism, and the prokaryotes form an endosymbiotic relationship with the host cell and gradually develop into mitochondria.(1) Mitochondria are considered to be responsible for several vital cellular activities, including energy production, regulation of apoptosis, hemostasis, and formation of heme proteins, among several other functions. All these functions appear to be regulated by mitochondria via their communications to the cell through several retrograde signals. These signals may be encoded by the nuclear genome present in the mitochondria, possibly due to its prokaryotic origin.(2) A small peptide called Humanin is derived from this genome. Since this genome appears to play an important role, this peptide has been explored for its potential action in several biological functions. Overview The peptide appears to exert potential actions via binding with intracellular molecules and cell membrane receptors, possibly inducing cytoprotective and/or neuroprotective functions.(9) Researchers suggest that Humanin may bind with the Bcl-2-associated X protein (also called Bax protein). Bax protein is considered to play a vital role in cellular death (apoptosis). Upon binding with the inactive form of the Bax protein, Humanin may inhibit the changes in the Bax protein and potentially thereby prevent cellular apoptosis.(9) Apart from research into its possible interaction with Bax, Humanin studies suggest the peptide may also bind with other intracellular molecules, such as actinin-4 and phosphoprotein 8, which are both involved in cellular apoptosis. Upon binding with these proteins, Humanin may induce cytoprotective actions. Researchers suggest Humanin may bind with two G protein-coupled peptide receptors, namely FPRL-1 and FPRL-2 receptors, which are considered to be involved with neurological function.(9) By binding with this receptor, Humanin may potentially prevent amyloid β binding with the FPRL-1 and FPRL-2 receptors, which may mitigate some instances of neurological degradation. Chemical Makeup Molecular Formula: C119H204N34O32S2 Molecular Weight: 2687.3 g/mol Other Known Titles: HNGF6A protein Research and Clinical Studies Humanin Peptide and Mitochondrial Functions Mitochondria appear to be susceptible to reactive oxygen species (ROS), and the presence of such ROS may reduce its functioning. Studies in Humanin mechanisms of action suggest that the peptide may inhibit these reactive oxygen species to some degree, thereby mitigating mitochondria degeneration.(10) One study was produced wherein the researchers attempted to explore the peptide's action on retinal pigment epithelial cells. These cells were isolated and introduced to tert-butyl hydroperoxide to exert oxidative stress in the cells. Some of these cells were then presented with Humanin peptide for 24 hours. When examined, the cells exposed to Humanin reportedly inhibited the formation of tert-butyl hydroperoxide-induced reactive oxygen species. The researchers suggested the peptide may have restored the bioenergetics in the retinal pigment epithelial cells and increased the functioning of mitochondria. Humanin Peptide and Cellular Longevity Studies(11) were conducted on several murine models to determine the relation between Humanin with growth hormone (GH) and immunoglobulin (IGF-1). In GH-transgenic murine models, the levels of growth hormone and IGF-1 appeared to be extremely high, which the researchers suggested led to increased body size, accelerated cell aging, and reduced life span. Researchers reported that the levels of Humanin naturally present in the murine models were extremely low, about 70% lower than the control. Another set of murine models had undetectable levels of GH and IGF-1, along with a reported 40% increase in the Humanin levels. These murine models showed an increased life span compared to normal murine models. These results supported the researchers' hypothesis that Humanin may be negatively correlated to GH and IGF-1 levels and directly correlated to cellular longevity. Humanin Peptide and Neurological Deterioration A study(12) was conducted on 9-month-old murine models, all of which reportedly possessed high levels of amyloid proteins. These amyloid chemicals are indicative of some neurological deterioration. Some murine models were presented with Humanin, while others were given a placebo. Following the study, the researchers suggested that the placebo models showed impaired memory and poor learning skills. In contrast, the murine models presented with Humanin for 3 months reportedly exhibited significantly improved learning ability and enhanced memory. In another study,(13) murine models with experimentally induced impairment in neurological functioning were exposed to Humanin and a similarly structured peptide, PAGA, to determine the potential of both peptides on the brain function of the murine models. Both the peptides showed some modest improvement in the impairment of the brain, as suggested by the researchers. Another study explored the potential neuroprotective action of Humanin on neurotoxicities induced by Calyculin A in cortical neurons as a model of exposure to neurotoxins. The researchers focused on the potential capability of the peptide to safeguard cortical neurons from Calyculin A-induced neurotoxic action. In this investigation, cortical neurons were preincubated with Humanin to examine its protective role against neurotoxicity. The methodologies utilized in this research included employing 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and Calcein-AM assays to evaluate the extent of neural damage. Furthermore, caspase 3 signaling and TUNEL assays were conducted to assess neural apoptosis. The study also used Western blot analysis to detect potential expressions of phosphorylated tau, a protein associated with neurodegenerative diseases. Additionally, the study measured the apparent contents of malondialdehyde (MDA) and superoxide dismutase (SOD), and the activity of protein phosphatase 2A (PP2A), which are potential indicators of oxidative stress in neurons. The results from these investigations posited that preincubation with Humanin may preserve cell viability and potentially protect neurons from Calyculin A-induced damage. Notably, the peptide appeared to alleviate oxidative stress in the neurons and preserved the activity of PP2A, an enzyme involved in dephosphorylating tau proteins. Humanin also may have inhibited the over-phosphorylation of tau at specific sites (Ser199/202, Ser396, and Thr231), which are considered critical to the pathological changes observed in neurodegenerative diseases. From these findings, it was inferred that Humanin potentially offered protective action against neurotoxicities induced by harmful agents like Calyculin A.(14) Humanin Peptide and Insulin Resistance To determine the potential of Humanin on insulin resistance, a study(15) was conducted on nonobese diabetic murine models. When a group of these models were presented with Humanin, it appeared to restore to some degree the levels of glucose tolerance within 6 weeks. Furthermore, Humanin also potentially delayed the onset of diabetes in the murine models presented with the peptide for 20 weeks. Researchers suggested that following the study results, Humanin may exhibit some action in insulin resistance. In another study,(16) 12-week-old murine models were subjected to a 60% high-fat diet and were presented with Humanin for 4 weeks. After the study, there appeared to be no difference in the food intake. However, the weight gain had reportedly been reduced by about 20%. Furthermore, there appeared to be a high expenditure of energy, decreased fasting glucose levels, and increased insulin levels. Another study also explored the potential role of Humanin in influencing insulin sensitivity. The investigation suggested that continuous exposure of Humanin to the central nervous system of murine models appeared to enhance overall insulin sensitivity. This improvement in insulin action seemed to be linked to the activation of STAT-3 (Signal Transducer and Activator of Transcription 3) signaling within the hypothalamus. However, this action was negated when hypothalamic STAT-3 was co-inhibited, suggesting a potential role of this signaling pathway in mediating Humanin actions on insulin sensitivity. Furthermore, centrally-acting Humanin also appeared to improve insulin resistance in peripheral tissues such as liver cells. Ultimately, this appeared to result in reduced blood glucose levels in the murine models.(17) Humanin Peptide and Hypoxia A study(18) was conducted in which the isolated retinal cells were exposed to cobalt chloride, which appeared to induce hypoxia, leading to cell apoptosis. When the hypoxia-induced cells were presented with Humanin, researchers reported that the peptide appeared to reverse the impact of cobalt chloride and protect the cell from reduced oxygen levels. Additional studies (19) have suggested that Humanin may possibly increase metabolic activity and, thereby, cell survival rates in the event of lymphocyte death, which has some implications in ischemia. Humanin Peptide and Ischemia This study(20) was conducted to further examine the neuroprotective potential of Humanin in the presence of cerebral ischemia. In this study, murine models were experimentally induced with cerebral artery occlusion. Murine models were presented with low concentrations of Humanin for 30 minutes and then, following the procedure, were reintroduced to Humanin at 0, 2, 4, and 6 hours after ischemia. Other murine models were solely presented with Humanin one hour before ischemia. It was suggested that continual introduction to the peptide appeared to reduce the ischemia volume by almost 30%. Humanin presence following ischemia reportedly further reduced the ischemic impact. Another study on Humanin investigating its potential in mitigating ischemia in cells suggests that the peptide may be capable of reducing infarct size in murine models.(21) In this notable study, researchers suggested that Humanin may exhibit a potential to significantly reduce infarct size by 41% in a large animal model when introduced alongside standard reperfusion intervention after an ischemic period of 60 minutes, followed by 48 hours of reperfusion. However, it is important to note that the beneficial action of Humanin was not observed when the ischemic period was extended to 75 minutes, followed by the same duration of reperfusion, highlighting a potentially critical window for Humanin. The study also highlights that Humanin has been implicated in various protective roles across multiple organs, attributed to the potential to modulate oxidative stress, regulate insulin sensitivity, and inhibit apoptotic signaling, among other actions. Humanin Peptide Additional Studies Studies(22) have suggested that Humanin may bind with the FPR2 receptor in the brain, producing possible anxiolytic action. Consequently, the researchers of this study suggested that Humanin may potentially reduce anxiety symptoms. In this study,(23) murine carcinogenesis models were exposed twice weekly with an antineoplastic agent (used in cancer cases) and Humanin to explore their potential impact on the carcinogenic cells. While the control agent appeared to induce cell apoptosis, the combination of Humanin and the agent exhibited some potential, somewhat reversing the apoptosis of the healthy cells. Humanin peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: The origin of mitochondria and chloroplasts. https://www.nature.com/scitable/content/the-origin-of-mitochondria-and-chloroplasts-14747702/ Lee, Changhan et al. “Humanin: a harbinger of mitochondrial-derived peptides?.” Trends in endocrinology and metabolism: TEM vol. 24,5 (2013). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641182/ Gong, Zhenwei et al. “Humanin and age-related diseases: a new link?.” Frontiers in endocrinology vol. 5 210. 4 Dec. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255622/ Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6336-41. https://pubmed.ncbi.nlm.nih.gov/11371646/ Yen K, Lee C, Mehta H, Cohen P. The emerging role of the mitochondrial-derived peptide humanin in stress resistance. J Mol Endocrinol. 2013 Jan 11;50(1):R11-9. https://pubmed.ncbi.nlm.nih.gov/23239898/ Gong, Zhenwei et al. “Humanin and age-related diseases: a new link?.” Frontiers in endocrinology vol. 5 210. 4 Dec. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255622/ Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, Satterthwait AC, Reed JC. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature. 2003 May 22;423(6938):456-61. https://pubmed.ncbi.nlm.nih.gov/12732850/ Ikonen M, Liu B, Hashimoto Y, Ma L, Lee KW, Niikura T, Nishimoto I, Cohen P. Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13042-7. https://pubmed.ncbi.nlm.nih.gov/14561895/ Gong, Zhenwei et al. “Humanin and age-related diseases: a new link?.” Frontiers in endocrinology vol. 5 210. 4 Dec. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255622/ Sreekumar PG, Ishikawa K, Spee C, Mehta HH, Wan J, Yen K, Cohen P, Kannan R, Hinton DR. The Mitochondrial-Derived Peptide Humanin Protects RPE Cells From Oxidative Stress, Senescence, and Mitochondrial Dysfunction. Invest Ophthalmol Vis Sci. 2016 Mar;57(3):1238-53. https://pubmed.ncbi.nlm.nih.gov/26990160/ Changhan Lee et al, IGF-I regulates the age-dependent signaling peptide humanin. Published 18 July 2014, Vol 13 Issue 5. https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12243 Zhang W, Zhang W, Li Z, Hao J, Zhang Z, Liu L, Mao N, Miao J, Zhang L. S14G-humanin improves cognitive deficits and reduces amyloid pathology in the middle-aged APPswe/PS1dE9 mice. Pharmacol Biochem Behav. 2012 Jan;100(3):361-9. https://pubmed.ncbi.nlm.nih.gov/21993310/ Krejcova G, Patocka J, Slaninova J. Effect of humanin analogues on experimentally induced impairment of spatial memory in rats. J Pept Sci. 2004 Oct;10(10):636-9. https://pubmed.ncbi.nlm.nih.gov/15526713/ Zhao, J., Zeng, Y., Wang, Y., Shi, J., Zhao, W., Wu, B., & Du, H. (2021). Humanin protects cortical neurons from calyculin A-induced neurotoxicities by increasing PP2A activity and SOD. The International journal of neuroscience, 131(6), 527–535. https://doi.org/10.1080/00207454.2020.1769617 Hoang PT, Park P, Cobb LJ, Paharkova-Vatchkova V, Hakimi M, Cohen P, Lee KW. The neurosurvival factor Humanin inhibits beta-cell apoptosis via signal transducer and activator of transcription 3 activation and delays and ameliorates diabetes in nonobese diabetic mice. Metabolism. 2010 Mar;59(3):343-9. https://pubmed.ncbi.nlm.nih.gov/19800083/ Zhenwei Gong et al, Central effects of humanin on hepatic triglyceride secretion, Endocrinology and Metabolism. Muzumdar, R. H., Huffman, D. M., Atzmon, G., Buettner, C., Cobb, L. J., Fishman, S., Budagov, T., Cui, L., Einstein, F. H., Poduval, A., Hwang, D., Barzilai, N., & Cohen, P. (2009). Humanin: a novel central regulator of peripheral insulin action. PloS one, 4(7), e6334. https://doi.org/10.1371/journal.pone.0006334 Men J, Zhang X, Yang Y, Gao D. An AD-related neuroprotector rescues transformed rat retinal ganglion cells from CoCl₂-induced apoptosis. J Mol Neurosci. 2012 May;47(1):144-9. doi: 10.1007/s12031-011-9701-5. Epub 2012 Jan 5. https://pubmed.ncbi.nlm.nih.gov/22222604/ Kariya S, Takahashi N, Hirano M, Ueno S. Humanin improves impaired metabolic activity and prolongs survival of serum-deprived human lymphocytes. Mol Cell Biochem. 2003 Dec;254(1-2):83-9. https://pubmed.ncbi.nlm.nih.gov/14674685/ Xu X, Chua CC, Gao J, Hamdy RC, Chua BH. Humanin is a novel neuroprotective agent against stroke. Stroke. 2006 Oct;37(10):2613-9. Epub 2006 Sep 7. https://pubmed.ncbi.nlm.nih.gov/16960089/ Sharp, T. E., 3rd, Gong, Z., Scarborough, A., Goetzman, E. S., Ali, M. J., Spaletra, P., Lefer, D. J., Muzumdar, R. H., & Goodchild, T. T. (2020). Efficacy of a Novel Mitochondrial-Derived Peptide in a Porcine Model of Myocardial Ischemia/Reperfusion Injury. JACC. Basic to translational science, 5(7), 699–714. Zhao H, Sonada S, Yoshikawa A, Ohinata K, Yoshikawa M. Rubimetide, humanin, and MMK1 exert anxiolytic-like activities via the formyl peptide receptor 2 in mice followed by the successive activation of DP1, A2A, and GABAA receptors. Peptides. 2016 Sep;83:16-20. https://pubmed.ncbi.nlm.nih.gov/27475912/ Emma Eriksson, Malin Wickström, Lova Segerström Perup, John I. Johnsen, Staffan Eksborg, Per Kogner, Lars Sävendahl, Protective Role of Humanin on Bortezomib-Induced Bone Growth Impairment in Anticancer Treatment, JNCI: Journal of the National Cancer Institute, Volume 106, Issue 3, March 2014, djt459, https://doi.org/10.1093/jnci/djt459 Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
MGF (5mg)
MGF stands for Mechano Growth Factor, an endogenous, naturally occurring peptide that belongs to the class of IGF-1 (insulin-like growth factor) family.(1) What differentiates MGF from systemic IGF-1 is that it contains 49 base pairs at exon 5 in its structural composition, which may possibly introduce a frameshift to exert unique characteristics.(2) Researchers consider MGF to be an isoform of IGF-1, also known as IGF-1Ec (otherwise referred to as full-length MGF).(3) As IGF-1 undergoes alternative splicing and transcription, it appears to produce three isoforms. IGF-1 undergoes splicing under stress conditions, such as during resistance activities within muscle groups.(4) As a result of this splicing and due to the unique 49 base pair insert added to the peptide, it may produce a mature isoform of IGF-1, namely, naturally occurring MGF.(4) Overview During IGF-1 research studies, scientists first posited the phenomenon of IGF-1 splicing and isoform production. The only factor identified by the researchers that distinguished the three isoforms appears to be the amino acid sequence attached to the COOH terminal. It was only in the late 1990s and early 2000s that the uniqueness of IGF-1Ec was suggested when it was theorized that its levels increased upon muscle injury.(5) There is a synthetic version of the MGF peptide composed of 24 amino acids attached to the C-terminal of the isolated MGF domain, called MGF-Ct24E peptide, or E-domain of IGF-1Ec.(6) During the studies conducted in the early 2000s,(6) it was suggested that the MGF-Ct24E peptide may exhibit potential to induce muscle precursor cell proliferation. Muscle precursor cells are ‘satellite’ cells in myofiber, which increase to form new muscles. MGF is posited to increase in a growth hormone-dependent fashion, akin to IGF-1, which is also considered to potentially represent the main anabolic mediator of growth hormone. Studies suggest that growth hormones may also impact MGF expression by approximately 80%, relative to the baseline. In stark contrast, resistance activity in muscle tissue alone appears to elicit a response in MGF mRNA, with an increase of 163% from baseline. This immediate response may suggest a more direct or sensitive reaction of MGF to mechanical stimuli, yet the extent and nature of this sensitivity remain speculative. An apparent elevation of growth hormone that occurs in addition to resistance training might further complicate this response, as supported by a reported 456% increase in MGF mRNA.(7) Research studies are still underway to determine the mechanism of action of both the naturally occurring and synthetically developed MGF peptide. Hypotheses under investigation include the peptide's potential impact on damaged muscle cells, tissue repair and recovery, possible neuroprotective and cardioprotective characteristics, and potential impact on muscle cell apoptosis. Chemical Makeup Molecular Formula: C124H204N42O41S1 Molecular Weight: 2971.99 g/mol Other Known Titles: MGF-E, MGF-Ct24E Research and Clinical Studies MGF Peptide and Muscle Mass The main aim of one critical study on MGF(8) was to determine the potential of the synthetic peptide, aka the MGF-E domain made of 24 amino acids, on different aged cells. This was a study where muscle cell cultures, which ranged from neonatal to aged, were evaluated. The culture cells were analyzed after exposure to MGF-E. The peptide seemed to delay the onset of cellular senescence in younger cells, suggesting a potential to preserve muscle function and repair capabilities that diminish naturally. Furthermore, the results suggested cell proliferation in all cells isolated from neonatal to young cells; however, this was not the case in aged cells. Muscle hypertrophy appeared to be increased in the older cells, with a significant decrease in the reserve cells. It appeared to have induced hypertrophy in muscle cells across all ages by increasing the fusion index and the size of myotubes, which are formed from the fusion of muscle cells. The researchers observed that MGF-E may potentially also increase the expression of muscle-specific contractile proteins, indicating not only an increase in muscle cell size but also in functional capacity. Furthermore, the reduction in reserve cells appears notable as this may be a subpopulation of cells that do not initially differentiate or fuse into myotubes. MGF-E apparently led to a decreased proportion of these reserve cells in culture, suggesting that the peptide might prompt these cells to contribute to muscle formation. This finding is particularly noteworthy as it points to a mechanism by which MGF might potentially enhance muscle regeneration and maintenance. MGF Peptide and Muscle Recovery The main aim of another study(9) was to evaluate the potential of MGF on skeletal muscle injury repair and healing. This study was performed on mice that were experimentally induced with muscle contusion. Following Mechano Growth Factor (MGF) exposure and analysis of the muscle tissues, researchers suggested that MGF may have reduced the expressions of inflammatory markers such as cytokines and chemokines. Further, there was an apparent reduction of oxidative stress markers and matrix metalloproteinases (MMPs), suggesting that MGF might mitigate some inflammatory and fibrotic responses in muscle injury. As a result, the rate of contused muscles appeared to decline, which might induce long-term muscular repair of the wounded tissues. Moreover, the study hints that MGF may potentially not markedly impact the functional state of satellite cells following injury and immune cell depletion at the injury site, which is integral to muscle regeneration. This inference is drawn from observing unaltered expression levels of MyoD and myogenin—key satellite cell proliferation and differentiation indicators, respectively. This suggests that while MGF might potentially ease certain aspects of the muscle injury response, its direct action on satellite cell activity under the explored conditions remains uncertain. Subsequent examinations suggest that MGF exposure might influence fibrosis in injured muscle by possibly reducing the expression of collagen types I and III, crucial for the extracellular matrix and fibrotic development. The study further hints that MGF may play a part in adjusting the inflammatory setting within injured muscles. This is somewhat illustrated by a purported reduction in the expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, TGF-β) and chemokines (CCL2, CCL5, CXCR4) post-MGF exposure. Moreover, there's a speculative suggestion that MGF might assist in alleviating oxidative stress in injured muscle, indicated by a possible decrease in the expression of gp91phox, a vital component of NADPH oxidase implicated in the production of reactive oxygen species. MGF Peptide and Anti-Apoptotic Potential The main goal of this study(10) was to evaluate the potential of MGF on cardiac muscles undergoing programmed cell death (apoptosis) following hypoxia, a condition characterized by limited supply of oxygen. The study reported that the peptide appeared to induce increased migration of stem cells to the heart tissues exposed to hypoxia, which possibly led to inhibition of apoptosis. This suggests that MGF may play a dual role in cardiac function, acting as a potential anti-apoptotic compound and a stem cell-homing factor. The researchers highlight that MGF potentially enhances the migration of mesenchymal stem cells (hMSCs), indicating a chemotactic action that might be leveraged to direct stem cells toward regions of damage or injury. Moreover, in an environment simulating hypoxic stress—a condition akin to that experienced by heart tissue during ischemic events—MGF is suggested to exhibit protective potential in cardiac cells. This hypothesis was raised by observation of increases in the expression of Bcl-2, a gene associated with cell survival, underscoring MGF's potential anti-apoptotic action. MGF Peptide and Skeletal Injury The main goal of this study(11) was to evaluate the potential of MGF on bone injury. A total of 27 rabbits were experimentally induced with a 5-mm bone defect and were then divided into three groups that were presented with MGF or with a control substance for 5 consecutive days. Post-study, the researchers reported that the placebo tissue appeared to be the least healed when the bone tissues were histologically examined. In contrast, the bone tissue with MGF appeared to be the most healed tissue. Regarding the potential impact on osteoblast-like cell proliferation, the investigation hints that MGF might potentially enhance proliferation. This enhancement appears to be more pronounced when compared with IGF-1, leading to the speculation that MGF may activate cellular mechanisms somewhat differently from IGF-1. The study points out that MGF might play a role in arresting the cell cycle in certain phases and could be involved in activating the MAPK-Erk1/2 signaling pathway. Such actions imply that MGF may have a complex approach to promoting cell proliferation, perhaps through a blend of influencing cell cycle dynamics and engaging specific signaling pathways. Moreover, the study ventured into assessing the possible actions of MGF utilizing a rabbit model with established bone defects. Here, MGF was introduced, and its influence on bone healing was monitored via radiographic and histological evaluations. The findings tentatively indicate that bone healing might be improved in defects exposed to MGF, as suggested by seemingly better rates of radiographically healed defects and improved histological scores for bone healing. MGF Peptide and Brain Ischemia The main purpose of a 2005 study(12) was to combat ischemic stroke through the potential action of MGF peptides. The actions were studied in experiments conducted on gerbil research models of brain ischemia. The synthetic Mechano Growth Factor peptide was presented as an ischemic mitigator. Researchers reported that MGF appeared to lead to increased protection of brain cells. Interestingly, in the same model, it was also reported that ischemia appeared to lead to elevated endogenous MGF production in the ischemia-resistant neurons. Additional studies were carried out in degenerated hippocampal cell culture, to which MGF was added. MGF exhibited reportedly similar results of muscle proliferation. This potential action is believed to be due to the C-terminal of the MGF peptide, which may exert some level of neuroprotective action. MGF Peptide and Brain Cells A notable study (13) was conducted on a murine model to study the action of increased MGF concentration on brain cells. One study included breeding mice to constitutively overproduce MGF in the hippocampus area of the brain. The hippocampus is primarily responsible for regulating the neurogenesis phenomenon in the organism. This overproduction of MGF appeared to result in high concentrations of BrdU, a biological marker representative of proliferative actions in the organism. More specifically, the mice were bred for conditional MGF production at 1, 3, and 12 months old. Behavioral analysis and biological responses were examined after 2 years. These mice were reported to exhibit elevated levels of BrdU and neurogenesis. MGF peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Philippou A, Papageorgiou E, Bogdanis G, Halapas A, Sourla A, Maridaki M, Pissimissis N, Koutsilieris M. Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro. In Vivo. 2009 Jul-Aug;23(4):567-75. https://pubmed.ncbi.nlm.nih.gov/19567392/ Goldspink G. Impairment of IGF-I gene splicing and MGF expression associated with muscle wasting. Int J Biochem Cell Biol. 2006 Mar;38(3):481-9. https://pubmed.ncbi.nlm.nih.gov/16463438/ Zabłocka, B., Goldspink, P. H., Goldspink, G., & Górecki, D. C. (2012). Mechano-Growth Factor: an important cog or a loose screw in the repair machinery? Frontiers in endocrinology, 3, 131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485521/ G Goldspink. Research on mechano growth factor: its potential for optimising physical training as well as misuse in doping. Department of Surgery, Royal Free and University College Medical School, Hampstead Campus, Rowland Hill Street, London NW3 2PF. https://bjsm.bmj.com/content/39/11/787 Rotwein P. (2014). Editorial: the fall of mechanogrowth factor?. Molecular endocrinology (Baltimore, Md.), 28(2), 155–156. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896639/ Mills P, Dominique JC, Lafrenière JF, Bouchentouf M, Tremblay JP. A synthetic mechano growth factor E Peptide enhances myogenic precursor cell transplantation success. Am J Transplant. 2007 Oct;7(10):2247-59. https://pubmed.ncbi.nlm.nih.gov/17845560/ Hameed M, Lange KH, Andersen JL, Schjerling P, Kjaer M, Harridge SD, Goldspink G. The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men. J Physiol. 2004 Feb 15;555(Pt 1):231-40. doi: 10.1113/jphysiol.2003.051722. Epub 2003 Oct 17. PMID: 14565994; PMCID: PMC1664832. Kandalla PK, Goldspink G, Butler-Browne G, Mouly V. Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages. Mech Ageing Dev. 2011 Apr. https://pubmed.ncbi.nlm.nih.gov/21354439/ Liu X, Zeng Z, Zhao L, Chen P, Xiao W. Impaired Skeletal Muscle Regeneration Induced by Macrophage Depletion Could Be Partly Ameliorated by MGF Injection. Front Physiol. 2019 May 17;10:601. https://pubmed.ncbi.nlm.nih.gov/31164836/ Doroudian, G., Pinney, J., Ayala, P., Los, T., Desai, T. A., & Russell, B. (2014). Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes. Biomedical microdevices, 16(5), 705–715. https://doi.org/10.1007/s10544-014-9875-z Deng M, Zhang B, Wang K, Liu F, Xiao H, Zhao J, Liu P, Li Y, Lin F, Wang Y. Mechano growth factor E peptide promotes osteoblasts proliferation and bone-defect healing in rabbits. Int Orthop. 2011 Jul;35(7):1099-106. https://pubmed.ncbi.nlm.nih.gov/21057789/ Dluzniewska J, Sarnowska A, Beresewicz M, Johnson I, Srai SK, Ramesh B, Goldspink G, Górecki DC, Zabłocka B. A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia. FASEB J. 2005 Nov;19(13):1896-8. https://pubmed.ncbi.nlm.nih.gov/16144956/ Tang JJ, Podratz JL, Lange M, Scrable HJ, Jang MH, Windebank AJ. Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain. Mol Brain. 2017 Jul 7;10(1):23. doi: 10.1186/s13041-017-0304-0. PMID: 28683812; PMCID: PMC5501366. Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.