Peptides
N-Acetyl Selank (10mg)
N-Acetyl Selank is a short, synthetic heptapeptide analogous to the naturally occurring peptide called Tuftsin.(1) Tuftsin is an endogenous tetrapeptide that appears to regulate the immune system. Selank peptide may exhibit immunomodulatory potential; however, it has also been studied in models of anxiety and cognitive decline for its nootropic potential. Apart from the homology with tuftsin, the peptide appears to have a Pro-Gly-Pro fragment at its C-terminus, which may provide an enhancement of Selank's potential to traverse through different tissues and models including the blood-brain barrier (BBB). The BBB is a highly selective, semi-permeable border that separates the circulating blood from the tissues and extracellular fluid in the central nervous system, and is considered to play a crucial role in regulating the passage of substances. Pro-Gly-Pro addition might enhance BBB permeability by potentially impacting the peptide's overall hydrophilicity or lipophilicity, thereby increasing its affinity for the lipid-rich environment of the BBB. Additionally, the Pro-Gly-Pro sequence may interact with specific transport mechanisms or receptors at the BBB, potentially triggering a facilitated transport or receptor-mediated endocytosis. Such processes might allow Selank to bypass the tight junctions that normally restrict the passage of large molecules. Pro-Gly-Pro fragment may also influence the peptide's tertiary structure in a way that makes it more conducive to crossing the BBB. Further, N-Acetyl Selank Amidate has an additional acetyl group attached to the N-terminus. Adding an acetyl group to the N-terminus in N-Acetyl Selank Amidate may improve the peptide's stability through several speculative mechanisms. Acetylation might potentially shield the peptide from rapid enzymatic degradation by exopeptidases, as it might make the N-terminus less accessible or recognizable to these enzymes. Additionally, acetylation may induce changes in the peptide's structure, possibly leading to a more stable conformation that resists denaturation. Overview Studies suggest that the Selank peptide produces possible action in several ways: Firstly, by potentially stimulating the gamma-aminobutyric acid (GABA) receptors system.(2) GABA is considered an inhibitory neurotransmitter in the brain, reducing neuronal excitability, promoting relaxation, and alleviating anxiety. Researchers have posited Selank to potentiate the capacity to induce changes in the expression of genes associated with GABA receptors, transporters, and ion channels. This implies that Selank might potentially influence GABAergic neurotransmission by modulating the availability or functionality of these key components. Furthermore, studies posit that Selank's actions may potentially extend beyond direct actions on GABA receptor gene expression to allosteric modulation of the GABAergic system. This is hinted at by the differential gene expression patterns observed following Selank and GABA exposure, wherein Selank appeared to have uniquely influenced the expression of certain genes. This nuanced action suggests that Selank may modulate the GABAergic system's function in a manner distinct from the straightforward receptor activation induced by GABA. Selank might also initiate longer-lasting alterations in neurotransmitter systems, potentially explaining its prolonged anxiolytic actions in experimental models. Secondly, the peptide may potentially interact with serotonin signaling.(3) Serotonin signaling in the brain is posited to regulate mood and anxiety. Experiments in murine models with blocked serotonin synthesis suggest that Selank may exert the potential to modulate serotonin levels under compromised serotonergic function. Selank was posited to enhance serotonin metabolism in the brainstem via a rapid onset of action on the serotonin system. Specifically, the peptide was suggested to promote increased metabolic activity of serotonin in parts of the brain linked to regulating mood and anxiety. Further, the study posits that Selank's potential to elevate serotonin metabolism indicates a possible mechanism through which Selank might correct disturbances associated with reduced serotonin function. Thirdly, the peptide may act by potentially modulating enkephalin signaling.(4)(5) Studies have posited that Selank may have an inhibitory action on enkephalin-degrading enzymes. This indicates that Selank might slow down the degradation of enkephalins. Enkephalins, as natural ligands of opioid receptors, are considered to play a role in pain perception and modulating mood and stress, implying that Selank’s action on these enzymes might enhance the availability of enkephalins, thereby potentially amplifying their actions. Studies also posit that there may be a tau(1/2) leu-enkephalin increase during Selank exposure in anxiety models. Finally, the peptide may potentially affect brain-derived neurotrophic factor (BDNF) expression.(8) Selank has been suggested to significantly elevate BDNF mRNA levels in the hippocampus, a part of the central nervous system. Selank's potential to enhance BDNF expression, especially in the context of stress and glucocorticoid-induced suppression of BDNF, points towards its potential research implications for ameliorating reduced neuroplasticity. Furthermore, researchers are currently investigating the potential actions of the peptide via genome expression and involvement in the inflammatory process.(7) Chemical Makeup(8) Molecular Formula: C33H57N11O9 Molecular Weight: 751.9 g/mol Other known titles: TP-7, Selanc Research and Clinical Studies Unfortunately, research on N-Acetyl Selank in its acetylated form is still sparse. However, the peptide is expected to have similar impacts as its unacetylated counterpart, Selank, with the addition possibly only affecting the peptide by providing higher stability. Because of this lack of research data, we cite only Selank studies below. N-Acetyl Selank and Anxiolytic Action In 2008, a clinical study(5) was conducted on research models of generalized anxiety disorder (GAD). The research models were divided into two groups – half were presented with allopathic anxiety compounds, and the other half were presented with Selank peptide. After completing this study, the psychometric levels of all models were examined. Based on the results, it was suggested that the Selank peptide appeared to be potentially as impactful as the control compound in reducing the models’ anxiety levels. The peptide-exposed group also exhibited reportedly positive psychostimulant reactions. As per A A Zozulia et al., “The clinical-biological study revealed that [models] with GAD and neurasthenia had the decreased level of tau(1/2) leu-enkephalin [...]. The increase of this parameter and stronger positive correlations with anxiety level were observed during the [exposure to] Selank.” N-Acetyl Selank and Anxiety In this clinical study,(9) research models of standard anxiety and phobia thresholds were examined. The research models were separated into an experimental and control group; the controls were exposed to an allopathic compound, and the experimental group was exposed to Selank peptide. After this study's completion, the results appeared to indicate the peptide's anxiolytic and nootropic potential. N-Acetyl Selank and Mental Cognition Research studies(10) evaluated experimental murine models following exposure to Selank peptide, after which the mice underwent ‘training’ exercises for four days to learn conditioned avoidance response (CAR). Observing the behavior of the models throughout the training period, researchers observed that the learning abilities of murine models appeared to improve as the number of errors reduced over time, compared to control models under the same conditions. These researchers suggested that the peptide may have exhibited nootropic potential. It is posited that such actions on learning and memory might involve several interconnected mechanisms, such as the modulation of neuropeptide systems in the brain, leveraging the potential role these peptides may play in cognitive functions to enhance learning and memory processes. Further, Selank may influence the neural pathways associated with memory consolidation, possibly improving synaptic stability and efficiency, deemed essential for learning. Selank might also facilitate cognitive performance indirectly by reducing anxiety-related parameters, which may often hinder learning efficiency, suggesting a role in the affective components of cognition. The peptide may also have the unique potential to enhance neural plasticity or resilience in underperforming cognitive circuits, thereby improving their functionality. N-Acetyl Selank and Immunomodulation Research models of anxiety and neurasthenia were evaluated in this study(11) following routine exposure to Selank for two weeks. After two weeks, blood samples were collected and analyzed. It was reported that there was a significant rise in the levels of interleukin-6 cytokines and alteration in the Th1 to Th2 cytokine ratio. As per O.N. Uchakina et al., "The cytokine regulating effects revealed in the study suggest that Selank [might act as] a novel immunomodulator in … anxiety-asthenic disorders. Additionally, the adaptogenic properties of Selank may benefit … environmental stressors to prevent infectious diseases.” N-Acetyl Selank and Substance Withdrawal A study(12) in experimental murine models infused the animals with 10% ethanol for 24 weeks. Upon discontinuing alcohol infusion, these murine models exhibited significant alcohol withdrawal symptoms. At this time, the peptide was then given to all affected murine models. 48 hours after the peptide, it was suggested by the researchers that the alcohol withdrawal symptoms were reportedly reduced in all murine models. N-Acetyl Selank and Cholesterol Control In one study,(13) murine models were subjected to a high-fat diet for six consecutive weeks until they gained a standard set weight. At that time, the models were divided into two groups – one exposed to a sodium chloride solution and the rest to the Selank peptide. Upon analysis, it was observed that the peptide group exhibited apparently improved fat metabolism, with a reported reduction of cholesterol levels up to 58%. Most notably, the researchers suggested that Selank may potentially decrease total cholesterol, low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) cholesterol, and triglycerides. This suggests Selank may have either a direct or indirect role in modulating lipid metabolism and may possibly exhibit hypocholesterolemic and/or hypolipidemic action. Furthermore, the study observed apparent improvements in hemostasis parameters, such as increased total fibrinolytic activity and a reduction in platelet aggregation, which might imply amelioration of prothrombotic states. The research also hints at a potential regulatory action of Selank on glucose homeostasis. N-Acetyl Selank peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References 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/ 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/ Semenova, T. P., kozlovskiĭ, I. I., Zakharova, N. M., & Kozlovskaia, M. M. (2009). Eksperimental'naia i klinicheskaia farmakologiia, 72(4), 6–8. Kost, N. V., Sokolov, O. I.u, Gabaeva, M. V., Grivennikov, I. A., Andreeva, L. A., Miasoedov, N. F., & Zozulia, A. A. (2001). Ingibiruiushchee deĭstvie semaksa i selanka na énkefalindegradiruiushchie fermenty syvorotki krovi cheloveka [Semax and selank inhibit the enkephalin-degrading enzymes from human serum]]. Bioorganicheskaia khimiia, 27(3), 180–183. https://doi.org/10.1023/a:1011373002885 Zozulia, A. A., Neznamov, G. G., Siuniakov, T. S., Kost, N. V., Gabaeva, M. V., Sokolov, O. I.u, Serebriakova, E. V., Siranchieva, O. A., Andriushenko, A. V., Telesheva, E. S., Siuniakov, S. A., Smulevich, A. B., Miasoedov, N. F., & Seredenin, S. B. (2008). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 108(4), 38–48. 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 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. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 11765600, Selank. https://pubchem.ncbi.nlm.nih.gov/compound/Selank 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/ 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.
N-Acetyl Semax (25mg)
N-Acetyl Semax is a synthetic polypeptide analogous to the naturally occurring adrenocorticotropic hormone (ACTH). The peptide is similar to a fragment from the adrenocorticotropic hormone ACTH (4-7), specifically Met-Glu-His-Phe, combined with a Pro-Gly-Pro extension at the C-terminus.(1) The addition of Pro-Gly-Pro (PGP) to N-Acetyl Semax might enable an enhanced permeability through the blood-brain barrier (BBB) by increasing the peptide's lipophilicity via improving passive diffusion or uptake via lipid raft-mediated endocytosis, which may potentially allow it to bypass the tight junctions of the BBB. The PGP addition at the C-terminus might also alter the peptide's interaction with specific BBB transporters or receptors, possibly promoting receptor-mediated transcytosis. Additionally, the acetylation of the peptide might increase its resistance to enzymatic degradation, prolonging its half-life in experimental models. Overview N-Acetyl Semax appears to exhibit potential nootropic (memory enhancing) and neuroprotective characteristics, which researchers have proposed may be produced via several routes: By potentially interacting with dopamine, serotonin, enkephalin, and brain-derived neurotrophic (BDNF) levels;(2)(3) Or by potentially modulating gene expression and increasing the efficacy of the immune system.(4) Based on studies suggesting that the peptide may inhibit serum enkephalin-degrading enzymes, it is plausible to hypothesize about the interactions between Semax and enkephalins. Researchers suggest Semax's inhibitory potential on enkephalin-degrading enzymes may lead to an increase in the levels of enkephalins by preventing their degradation. Enkephalins are endogenous opioids that are considered to play roles in nociception and stress response. Further, an increase in enkephalin levels might also influence other neurotransmitter systems due to the complex interplay between the opioid system and neurotransmitters like dopamine and serotonin.(2) According to studies, Semax may potentially increase the striatal levels of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, suggesting a possible enhancement of serotonergic activity. This potential action on serotonin metabolism might amplify serotonin-mediated pathways, possibly influencing central nervous system functioning. On the other hand, Semax does not appear to directly alter dopamine levels or its metabolites. Still, it may modulate the dopaminergic system's responsiveness, enhancing the dopaminergic agonists' action.(5) Chemical Makeup(6) Molecular Formula: C37H51N9O10S Molecular Weight: 858.97 g/mol Other known titles: ACTH (4-7)PGP, HY-P1146 Research and Clinical Studies N-Acetyl Semax and Nootropic Potential A study(5) was conducted on experimental rodents to determine the nootropic potential of ACTH hormone and its analogs, such as Semax. After exposure to Semax, all tested rodents were examined for 5-hyrodxyindoleacetic acid (5-HIAA) levels. Based on the results, it was noted that the 5-HIAA levels increased by 25% after just 2 hours following exposure; they increased progressively up to a maximum of 180% after 4 hours. As per Kirill O Eremin et al., “Our results reveal the positive modulatory [action] of Semax on the striatal serotonergic system and the ability of Semax to enhance both the striatal release of dopamine and locomotor behavior elicited by D-amphetamine.” In another research study,(7) experimental models under excessive stress conditions were exposed to Semax. Upon analyzing behavior 24 hours after peptide exposure, it was noted that they appeared to show signs of enhanced memory and attention. As per the reports, "In the majority of cases, the peptide exhibited positive [actions], and in no case did it produce negative side actions or complications connected with its administration. There is good reason to believe that … potentialities of Semax have not been exhausted and in the future new possibilities … will be revealed." The study is shared here for educational and research purposes, and studies on the Semax peptide are still being conducted. N-Acetyl Semax and SSRI Interaction Selective Serotonin reuptake inhibitors (SSRIs) are a class of antidepressants. In pregnant research models, the compounds may risk passing through the placenta and impacting fetal brain development. In a preclinical research study,(8) experimental rats aged between 1 and 14 days were presented first with an SSRI compound, followed by the Semax peptide. After 4 weeks, it was observed that the rats exposed to SSRIs showcased anxious behavior, especially when exposed to new stimuli. When they were given the Semax peptide, these same rats later reportedly exhibited a reduction in their anxiety levels and potential enhancement in their learning abilities. N-Acetyl Semax and Separation Anxiety Young offspring face separation anxiety when they are away from their mothers. Separating for a prolonged period may lead to impaired emotional reactivity. A research study(9) examined young rats facing maternal deprivation. After four weeks of separation from their mothers, these rats reportedly exhibited increased anxiety and excessive physical activity. When the rats were presented with Semax, their reactions improved, indicating reduced anxiety. As per M. A. Volodina et al., these results suggest that “Semax [weakens] the impact of deprivation on animal body weight and [normalizes] the levels of anxiety in rats.” N-Acetyl Semax and the Cardiovascular System For this study,(10) rodents were induced with myocardial infarction (MI), which may lead to vascular damage. These rodents were then divided into two groups – one was given Semax peptide for six days, and the second was given a placebo. Following 28 days after the occurrence of myocardial infarction, it was reported by the researchers that the control rodents appeared to exhibit reduced arterial blood pressure and cardiac hypertrophy, both of which may signal impending heart failure. In contrast, the peptide-exposed rodents reportedly exhibited signs of prevention of diastolic blood pressure, which may indicate possible remodeling of the heart ventricle and inhibition of heart failure. N-Acetyl Semax and Neuroprotection In a clinical study,(11) research models of ischemic strokes were evaluated for 10 days. Of these, 30% were presented with conventional compounds and the Semax peptide, while the remaining 70% were presented with conventional compounds only. After 10 days, all models were examined via electroencephalogram (EEG). Based on the EEG mapping, the researchers reported that the experimental group exposed to both the peptide and compound exhibited apparently notable improvement in restoring damaged brain activity. N-Acetyl Semax peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References T. Kolomin et al., A New Generation of Drugs: Synthetic Peptides based on Natural Regulatory peptides. Neuroscience & Medicine, 2013, 223-252. Published Online December 2013. http://dx.doi.org/10.4236/nm.2013.44035 Kost NV, Sokolov OIu, Gabaeva MV, Grivennikov IA, Andreeva LA, Miasoedov NF, Zozulia AA. Ingibiruiushchee deĭstvie semaksa i selanka na énkefalindegradiruiushchie fermenty syvorotki krovi cheloveka [Semax and selank inhibit the enkephalin-degrading enzymes from human serum]]. Bioorg Khim. 2001 May-Jun;27(3):180-3. Russian. doi: 10.1023/a:1011373002885. PMID: 11443939. https://pubmed.ncbi.nlm.nih.gov/11443939/ Shih-Jen Tsai, Semax, an analogue of adrenocorticotropin (4–10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome, Medical Hypotheses, Volume 68, Issue 5, 2007, Pages 1144-1146. https://doi.org/10.1016/j.mehy.2006.07.017 Medvedeva, E.V., Dmitrieva, V.G., Povarova, O.V. et al. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics 15, 228 (2014). https://doi.org/10.1186/1471-2164-15-228 Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005 Dec;30(12):1493-500. doi: 10.1007/s11064-005-8826-8. PMID: 16362768. https://pubmed.ncbi.nlm.nih.gov/16362768/ National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 9811102, Semax. Asmarin IP, Nezavibat'ko VN, Miasoedov NF, Kamenskiĭ AA, Grivennikov IA, Ponomareva-Stepnaia MA, Andreeva LA, Kaplan AIa, Koshelev VB, Riasina TV. Nootropnyĭ analog adrenokortikotropina 4-10-semaks (15-letniĭ opyt razrabotki i izucheniia) [A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its design and study)]. Zh Vyssh Nerv Deiat Im I P Pavlova. 1997 Mar-Apr;47(2):420-30. Russian. PMID: 9173745. https://pubmed.ncbi.nlm.nih.gov/9173745/ Nataliya Yu. Glazova, Daria M. Manchenko, Maria A. Volodina, Svetlana A. Merchieva, Ludmila A. Andreeva, Vladimir S. Kudrin, Nikolai F. Myasoedov, Natalia G. Levitskaya, Semax, synthetic ACTH(4–10) analog, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats, Neuropeptides, Volume 86, 2021, 102114, ISSN 0143-4179. https://doi.org/10.1016/j.npep.2020.102114 Volodina MA, Sebentsova EA, Glazova NY, Levitskaya NG, Andreeva LA, Manchenko DM, Kamensky AA, Myasoedov NF. Semax attenuates the influence of neonatal maternal deprivation on the behavior of adolescent white rats. Bull Exp Biol Med. 2012 Mar;152(5):560-3. English, Russian. doi: 10.1007/s10517-012-1574-2. PMID: 22803132. https://pubmed.ncbi.nlm.nih.gov/22803132/ Gavrilova SA, Golubeva AV, Lipina TV, Fominykh ES, Shornikova MV, Postnikov AB, Andrejeva LA, Chentsov IuS, Koshelev VB. [Protective effect of peptide semax (ACTH(4-7)Pro-Gly-Pro) on the rat heart rate after myocardial infarction]. Ross Fiziol Zh Im I M Sechenova. 2006 Nov;92(11):1305-21. Russian. PMID: 17385423. https://pubmed.ncbi.nlm.nih.gov/17385423/ Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat'ko VN, Zhuravleva EIu, Vanichkin AV. Effektivnost' semaksa v ostrom periode polusharnogo ishemicheskogo insul'ta (klinicheskoe i élektrofiziologicheskoe issledovanie) [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. Russian. PMID: 11517472. https://pubmed.ncbi.nlm.nih.gov/11517472/ 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.
Mod GRF 1-29 & Ipamorelin Blend (10mg)
The Ipamorelin peptide has been studied for its potential as a growth hormone secretagogue (GHS). This synthetic pentapeptide is thought to operate in a manner akin to Growth Hormone Releasing Peptides (GHRPs) and may simulate the natural action of the hunger hormone, ghrelin. Specifically, it is believed that Ipamorelin may activate ghrelin receptors in the anterior pituitary gland, also known as Growth Hormone Secretagogue Receptors 1 Alpha (GHS-R1a). This makes it a notably selective secretagogue and a strong agonist for the growth hormone/ghrelin secretagogue receptor. What sets Ipamorelin apart is its selectivity, as it does not appear to influence the release of other hormones from the pituitary gland, such as prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), or Adrenocorticotropic hormone (ACTH). Modified GRF (1-29) peptide, also known as Mod GRF 1-29, is a synthetic analog of natural growth hormone-releasing hormone (GHRH). Comprising the initial 29 amino acids of the native hormone, this analog appears to stimulate GHRH receptors located in the somatotroph cells of the anterior pituitary gland, thereby facilitating the release of growth hormone. While it shares structural similarities with GRF 1-29, Mod GRF 1-29 has been slightly altered by replacing four amino acids in its original sequence. These adjustments seem to improve the peptide's pharmacokinetic properties. When presented together as a blend, these peptides appear to yield synergistic results, possibly stimulating the pituitary gland and triggering the release of growth hormone. Chemical Makeup (1)(2)(3) Molecular Formula: Modified GRF 1-29: C152H252N44O42 Ipamorelin: C38H49N9O5 Molecular Weight: Modified GRF 1-29: 3367.95 g/mol Ipamorelin: 711.86 g/mol Other Known Titles Modified GRF 1-29: Mod GRF 1-29, CJC-1295 without DAC Ipamorelin: Ipamorelin Acetate, Aib-His-D-2-Nal-D-Phe-Lys-NH2 Research and Clinical Studies Mod GRF 1-29 & Ipamorelin Blend General Research A 1998 study(4) was carried out where these growth hormone secretagogues were presented in the rat pituitary gland as well as in anesthetized rats and conscious swine. Results of all three studies suggested that these peptides are agonists of GHRP-like receptors, as they bind to these receptors and help secrete higher concentrations of growth hormone. While some growth hormone secretagogues also appeared to trigger increased levels of other hormones such as cortisol and ACTH, Ipamorelin and Modified GRF 1-29 peptides appeared to exhibit selectivity towards growth hormones only, suggesting that these peptides may be particular in their functions. In one 1999 clinical study,(5) eight test subjects were enrolled to examine the potential of growth hormone secretagogues at different concentrations. The concentrations were increased every 15 minutes for up to two hours. After the study was completed, the concentration of growth hormones appeared to have significantly risen throughout the study period. Mod GRF 1-29 & Ipamorelin Blend and Potency In this preliminary study,(6) experimental rats were examined after being introduced to GHRH peptide analogs such as Modified GRF 1-29 peptide. The results suggested that the peptide may be considerably more potent than regular GRF 1-29. Mod GRF 1-29 & Ipamorelin Blend and the Pituitary When Mod GRF 1-29 interacts with GHRH receptors on the somatotroph cells of the anterior pituitary gland, it is theorized to act as a catalyst for ensuing cellular activities that may contribute to the release of growth hormone. This interaction is thought to set off a chain of intracellular signaling events. One such signaling route that seems to be engaged is the adenylyl cyclase pathway, potentially leading to the transformation of ATP (adenosine triphosphate) into cAMP (cyclic adenosine monophosphate).(7) The subsequent elevation in cAMP levels is speculated to activate protein kinase A (PKA), which in turn may result in the phosphorylation of various proteins. Among these proteins are the voltage-dependent calcium channels located on the cell membrane. The phosphorylation of these channels is conjectured to facilitate the influx of calcium ions into the somatotrophic cells. Elevated levels of intracellular calcium are considered to be a key factor in the subsequent stages that may lead to growth hormone release. It is further theorized that these high calcium concentrations within the cell could prompt the secretory vesicles in the somatotroph cells to release growth hormone into the bloodstream. It seems that Ipamorelin may also engage with cells in the front part of the pituitary gland by targeting the N-terminal region of GHS-R1a. This region contains specific binding sites that are likely sensitive to particular sequences in the secretagogue. When Ipamorelin encounters this receptor, it may form a temporary bond, facilitated by hydrogen bonds and van der Waals interactions. This transient bonding may induce a conformational change in the receptor, potentially triggering intracellular signaling pathways, predominantly those associated with G-proteins.(8) Specifically, GHS-R1a is thought to collaborate with a specialized subunit of G-proteins known as Gαq/11. Gαq/11 is believed to interact with PLC, which may then cleave a lipid molecule called phosphatidylinositol 4,5-bisphosphate (PIP2) into two secondary messengers: IP3 (Inositol trisphosphate) and DAG (Diacylglycerol). IP3 may bind to specific sites on an organelle known as the endoplasmic reticulum, possibly leading to the release of calcium ions (Ca2+) and activation of proteins that facilitate the secretion of growth hormone from pituitary cells.(9) Mod GRF 1-29 & Ipamorelin Blend and the Gastrointestinal System In a particular study, scientists explored how Ipamorelin might influence gastric function, specifically focusing on its potential to accelerate gastric emptying. They used a specialized method to measure gastric emptying, which involves tracking the percentage of radioactivity remaining in the stomach 15 minutes after introducing a specific substance via intragastric gavage. The team noted that the surgical procedures performed on the abdomen could have contributed to a slower rate of gastric emptying, especially evident in the control group that received a vehicle substance. Contrastingly, Ipamorelin seemed to significantly hasten the emptying process when compared to the control group. This led the researchers to consider the possibility that Ipamorelin could enhance the speed of gastric emptying. Further investigations were carried out to understand the compound's impact on the contractile behavior of gastric smooth muscles, which were stimulated by acetylcholine and electrical field stimulation. The findings indicated that surgical intervention and manipulation of the intestines might substantially suppress the contractile responses of these muscles to both stimuli. Interestingly, this suppression appeared to be counteracted when both Ipamorelin and ghrelin were introduced together. This raises the speculative notion that Ipamorelin may not only stimulate the contractility of gastric smooth muscles but also potentially negate the inhibitory action induced by certain surgical procedures.(10) Mod GRF 1-29 & Ipamorelin Blend and Appetite The potential impact of Ipamorelin on ghrelin receptors suggests it may possibly boost appetite and, maybe, contribute to weight gain. A study indicates that experimental subjects experienced an approximate 15% increase in body weight when exposed to Ipamorelin.(11) Researchers theorize that this compound may have proportionally increased fat pad weights relative to overall body mass.(11) As a result, dual-energy X-ray absorptiometry (DEXA) measurements may show a relative uptick in body fat. Additionally, data suggests that Ipamorelin may have raised levels of serum leptin, a hormone implicated in regulating energy and appetite. This leads scientists to hypothesize that increased food intake may be a factor in the observed weight gain among the Ipamorelin groups. They commented that “GHSs increase body fat by GH-independent mechanisms that may include increased feeding.” Mod GRF 1-29 & Ipamorelin Blend and Bone Density In a study involving murine models, Ipamorelin and a control substance were introduced to assess their potential on bone mass. Real-time DEXA was employed to monitor changes in bone mineral content, focusing on specific regions like the femur and L6 vertebrae. After the research period, mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans were conducted on the femurs of the subjects. Initial findings indicate that Ipamorelin may be linked to a potential increase in weight as well as a possible uptick in bone mineral content in the tibia and vertebrae, as revealed by DEXA, when compared to the control group. Moreover, pQCT data suggests that the observed rise in cortical BMC may be attributable to an enlargement in the bone's cross-sectional area.(12) The researchers also posited that “small stimulatory effects on linear bone growth may not have been detected statistically in the GH- and ipamorelin-treated groups,” Mod GRF 1-29 & Ipamorelin 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. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 9831659, Ipamorelin. https://pubchem.ncbi.nlm.nih.gov/compound/Ipamorelin. Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005 Jul;146(7):3052-8. doi: 10.1210/en.2004-1286. Epub 2005 Apr 7. PMID: 15817669. https://pubmed.ncbi.nlm.nih.gov/15817669/ Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61. doi: 10.1530/eje.0.1390552. PMID: 9849822. https://pubmed.ncbi.nlm.nih.gov/9849822/ Gobburu, J.V.S., Agersø, H., Jusko, W.J. et al. Pharmacokinetic-Pharmacodynamic Modeling of Ipamorelin, a Growth Hormone Releasing Peptide, in Human Volunteers. Pharm Res 16, 1412–1416 (1999). https://doi.org/10.1023/A:1018955126402 Schally AV, Zhang X, Cai R, Hare JM, Granata R, Bartoli M. Actions and Potential Therapeutic Applications of Growth Hormone-Releasing Hormone Agonists. Endocrinology. 2019 Jul 1;160(7):1600-1612. https://pubmed.ncbi.nlm.nih.gov/31070727/ Sinha, D. K., Balasubramanian, A., Tatem, A. J., Rivera-Mirabal, J., Yu, J., Kovac, J., Pastuszak, A. W., & Lipshultz, L. I. (2020). Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Translational andrology and urology, 9(Suppl 2), S149–S159. https://doi.org/10.21037/tau.2019.11.30 Yin, Y., Li, Y., & Zhang, W. (2014). The growth hormone secretagogue receptor: its intracellular signaling and regulation. International journal of molecular sciences, 15(3), 4837–4855. https://doi.org/10.3390/ijms15034837 Bill, C. A., & Vines, C. M. (2020). Phospholipase C. Advances in experimental medicine and biology, 1131, 215–242. https://doi.org/10.1007/978-3-030-12457-1_9 Greenwood-Van Meerveld, B., Tyler, K., Mohammadi, E., & Pietra, C. (2012). Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. Journal of experimental pharmacology, 4, 149–155. https://doi.org/10.2147/JEP.S35396 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 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 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.
CJC-1295 & GHRP-6 Blend (10mg)
Research indicates that peptides CJC-1295 and GHRP-6 may exert potential action on growth hormone release. When presented as a blend, they may possibly induce synergistic action, stimulating an organism’s synthesis and secretion of growth hormones. This peptide blend may possibly help repair mild injuries associated with muscles and surrounding ligaments. GHRP-6 peptide is a synthetic six amino acid peptide analog of ghrelin, a naturally occurring peptide that is considered by scientists to stimulate the secretion of growth hormones and help maintain their concentrations.(1) To do so, researchers hypothesize that it may activate what is known as the growth hormone secretagogue receptor (GHS-R1a). In terms of structure, GHRP-6 does not appear to share any homology with ghrelin despite its affinity to the receptors, but instead it appears to be an opioid analog of the peptide Met-enkephalin. Yet, researchers suggest it lacks the opioid activity which is typically associated with these enkephalins. Thus, GHRP-6 is a synthetic hexapeptide that researchers have classified in the group of growth hormone secretagogues (GHSs). CJC-1295, also referred to as tetra-substituted GRF (1-29), is a synthetic peptide analog of the naturally occurring growth hormone-releasing hormone (GHRH), which is believed by researchers to trigger the release of growth hormones.(2) It is essentially equivalent to the shortest chain of amino acids that may potentially attach to the GHRH receptors, which are the first 29 amino acids of GHRH. The key structural distinctions between CJC-1295 and GRF (1-29) are found in four altered amino acids of the original 29 amino acids of GHRH. These modifications involve the 2nd, 8th, 15th, and 27th amino acids, and may potentially enhance the peptide's resistance to degradation by the enzyme dipeptidyl peptidase-4. Specifically, the modifications include: The substitution of L-alanine with D-alanine at the 2nd position which is believed to increase resistance to molecular breakdown. Replacing asparagine with glutamine at the 8th position which may potentially reduce asparagine rearrangement and amide hydrolysis. The replacement of glycine with alanine at the 15th position which is hypothesized to augment bioactivity. Changing methionine with leucine at the 27th position which is posited to inhibit methionine oxidation. Chemical Makeup(2)(3) Molecular Formula: CJC-1295 peptide: C152H252N44O42 GHRP-6 peptide: C46H56N12O6 Molecular Weight: CJC-1295 peptide: 3367.9 g/mol GHRP-6 peptide: 873.0 g/mol Other Known Titles: Growth hormone-releasing hexapeptide CJC-1295 with DAC CJC-1295 without DAC Both forms of the CJC-1295 peptide essentially exert the same action; however, the addition of DAC (known as the drug affinity complex) appears to change the duration of the action of the peptide. CJC-1295 with DAC may have a longer-lasting action than CJC-1295 without DAC. This could be attributed to the proposed ability of the DAC to attach itself to proteins in the plasma. Specifically, the DAC element involves the connection of a lysine derivative, namely N-epsilon-3-maleimidopropionamide, to the C terminus of CJC-1295. The fusion of this altered amino acid sequence with the DAC element may possibly boost the pharmacokinetics of CJC-1295, prolonging its coexistence with plasma proteins to roughly 8 days, while concurrently preserving a noticeable affinity towards GHRH receptors, akin to the affinity demonstrated by CJC-1295 without DAC. Research and Clinical Studies CJC-1295 & GHRP-6 Peptide Blend and Growth Hormone Levels A clinical trial(4) was conducted in male test subjects aged between 20 and 40. All subjects were divided into two groups; one was presented with a placebo, and the rest received the CJC-1295 peptide. A blood sample was collected from all the subjects before and after peptide presence. Based on these samples, researchers reported that the peptide possibly contributed to a 7.5-fold increase in the subjects’ growth hormone levels compared to the placebo group. The growth hormone levels appeared to increase gradually and remained unchanged one week after the peptide presence. In another clinical study,(5) the peptide was given in ascending concentrations in a group of test subjects aged between 20 and 60. All subjects were divided into two groups – one was presented with the peptide, while the other with a placebo. After the end of the study, when blood samples were examined, it was noted that there appeared to be concentration-dependent action, up to 10-fold, in the levels of the subjects’ growth hormones. As per Madalina Ionescu, et al., “The marked enhancement of trough GH levels by continuous GHRH stimulation implicates the importance of this effect on increasing IGF-I. Long-acting GHRH preparations may benefit patients with intact pituitary GH secretory capability.” IGF-1 stands for insulin-like growth factor-1. It is considered by researchers to be the main anabolic mediator of growth hormone. In a clinical study focusing on the GHRP-6 peptide,(6) younger test subjects between 6 and 11 were presented with the peptide. Some were only given the peptide, while the rest were presented with a blend of peptide and arginine (a growth hormone booster). After the completion of the study, it was reported by the researchers that the growth hormone levels appeared to have increased exponentially and in equal concentrations in all subjects, seemingly regardless of the presence of arginine. CJC-1295 & GHRP-6 Peptide Blend and Hypothyroidism Hypothyroidism is characterized by low levels of growth hormones in an organism. In a 1997 clinical study,(7) subjects with hypothyroidism were presented with either GHRP-6 peptide, GHRH peptide, or a blend of peptides (such as CJC-1295) and GHRP-6. Post-study, it was reported that subjects presented with the blend exhibited apparently significantly higher levels of growth hormones than the individual peptides alone. The GHRP-6 peptide is considered to be an antagonist of somatostatin, which may be an inhibitor of growth hormone secretion. Due to this, the peptide blend appeared to yield a higher result. As per F R Pimentel-Filho et al., “When GHRP-6 was associated with GHRH, a significant increase in the GH response was observed in these patients, which could suggest a role for somatostatin in this process. Our data suggest that thyroid hormones modulate GH release induced by GHRH and GHRP-6 through different mechanisms. However, additional studies are necessary to elucidate this hypothesis further.” CJC-1295 and GHRP-6 Peptide Blend and Cellular Repair Experimental animal models were induced with injury and multiple organ failure. They were then presented with either the GHRP-6 peptide or a combination of GHRP-6 and epidermal growth factor (EGF). Based on the laboratory results, it was observed that the peptide might affect the gut epithelial cells of these animal subjects, as well as possibly increasing cellular migration at three times the usual rate. In addition, it appeared to reduce any adverse action of such failure by 50-85%.(8) GHRP-6 might also show a preference for CD36 receptors, potentially found on the surface of many cell types, such as fat cells, muscle cells, and immune cells. These receptors could have various potential functions, such as participating in fat metabolism, acting as a collector receptor for fats, aiding their absorption, and maybe influencing immune reactions and inflammation. The pathways of CD36 might also have a part in regulating the formation of new blood vessels. By potentially affecting inflammation and angiogenesis, GHRP-6 may further help improve cellular repair in various tissues. CJC-1295 and GHRP-6 Peptide Blend and Diabetes-Induced Gastrointestinal Activity Diabetes is considered by scientists to significantly impact the gastrointestinal system and may reduce the gastric emptying rate and colonic and intestinal transit. Research(9) conducted on experimental mouse models induced with diabetes were subjected to growth hormone release-stimulating peptides (such as GHRP-6). The peptide presence appeared to increase the rate of gastric emptying and intestinal transit, suggesting the peptide’s action in reversing the impacts induced by diabetes. No change was seen in the colonic transit. As per Zheng Q et al., peptides such as GHRP-6 “[have…] potential […] [for] delayed upper gastrointestinal transit.” CJC-1295 and GHRP-6 Peptide Blend and Heart Rate Preliminary research(10) was conducted in mice that suggested GHRH derivative analogs (such as the CJC-1295 peptide) may have the potential to stabilize heart rate and improve functionality following a heart attack. Andrew V. Schally et al. reported that the peptide appears to promote cardiac tissue repair and improve the blood pump capacity of the heart. The researchers observed that the results “[suggest] that GHRH agonists promote repair of cardiac tissue, improving ejection fraction and reducing infarct size in rats, reducing infarct scar in swine, and attenuating cardiac hypertrophy in mice.” CJC-1295 & GHRP-6 Peptide Blend and Neuroprotection The GHRP-6 peptide may be linked to the protection and repair of nervous tissue. A study examined its potential on the IGF-1 system in the brains of murine models.(11) GH potential actions are typically thought to be channeled through IGF-1, so the research focused on how the brain's IGF-1 system is influenced. It was found that a one-week exposure to GHRP-6 seemed to boost IGF-1 mRNA levels in the hypothalamus, cerebellum, and hippocampus, but not the cerebral cortex. This hints that GH and GHRP-6 may potentially boost IGF-1 expression in certain brain regions. The study also looked into the expression of the IGF receptor and IGFBP-2, an IGF-binding protein, but no significant variations in activity were found after the peptide was introduced. Nonetheless, the phosphorylation of Akt and Bad might have been triggered in regions where IGF-1 levels rose. This suggests that GH and GHRP-6 might activate intracellular pathways related to cell survival in response to growth factors. Bad is part of the Bcl-2 protein family, which plays a crucial role in cell death. In contrast, Akt is a protein kinase involved in various cellular functions like glucose metabolism, apoptosis, cell growth, transcription, and cell movement. No changes were noted in MAPK, another protein kinase, or glycogen synthase kinase-3beta. Additionally, the antiapoptotic protein Bcl-2 was found to be elevated in regions with increased IGF-1, while the proapoptotic protein Bax remained unchanged. This may imply a move towards cell survival and away from apoptosis. Finally, IGFBP-5, which is considered to be part of neuron survival processes, was mainly elevated in the hypothalamus, indicating a possible neuroendocrine function. CJC-1295 and GHRP-6 blend is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References Berlanga-Acosta, Jorge, et al. “Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects.” Clinical Medicine Insights. Cardiology vol. 11 1179546817694558. 2 Mar. 2017, doi:10.1177/1179546817694558. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392015/ 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. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 9919153, Growth hormone releasing hexapeptide. https://pubchem.ncbi.nlm.nih.gov/compound/9919153. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006 Dec;91(12):4792-7. doi: 10.1210/jc.2006-1702. Epub 2006 Oct 3. PMID: 17018654. https://pubmed.ncbi.nlm.nih.gov/17018654/ Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006 Mar;91(3):799-805. doi: 10.1210/jc.2005-1536. Epub 2005 Dec 13. PMID: 16352683. https://pubmed.ncbi.nlm.nih.gov/16352683/ Bellone J, Ghizzoni L, Amaretti G, Volta C, Boghen MF, Bernasconi S, Ghigo E. Growth hormone-releasing effect of oral growth hormone-releasing peptide 6 (GHRP-6) administration in children with short stature. Eur J Endocrinol. 1995 Oct;133(4):425-9. https://pubmed.ncbi.nlm.nih.gov/7581965/ Pimentel-Filho FR, Ramos-Dias JC, Ninno FB, Façanha CF, Liberman B, Lengyel AM. Growth hormone responses to GH-releasing peptide (GHRP-6) in hypothyroidism. Clin Endocrinol (Oxf). 1997 Mar;46(3):295-300. https://pubmed.ncbi.nlm.nih.gov/9156038/ Cibrián D, Ajamieh H, Berlanga J, León OS, Alba JS, Kim MJ, Marchbank T, Boyle JJ, Freyre F, Garcia Del Barco D, Lopez-Saura P, Guillen G, Ghosh S, Goodlad RA, Playford RJ. Use of growth-hormone-releasing peptide-6 (GHRP-6) for the prevention of multiple organ failure. Clin Sci (Lond). 2006 May;110(5):563-73. https://pubmed.ncbi.nlm.nih.gov/16417467/ Zheng, Q., Qiu, W. C., Yan, J., Wang, W. G., Yu, S., Wang, Z. G., & Ai, K. X. (2008). Prokinetic effects of a ghrelin receptor agonist GHRP-6 in diabetic mice. World journal of gastroenterology, 14(30), 4795–4799. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739343/ Schally AV, Zhang X, Cai R, Hare JM, Granata R, Bartoli M. Actions and Potential Therapeutic Applications of Growth Hormone-Releasing Hormone Agonists. Endocrinology. 2019 Jul 1;160(7):1600-1612. doi: 10.1210/en.2019-00111. PMID: 31070727. Frago LM, Pañeda C, Dickson SL, Hewson AK, Argente J, Chowen JA. Growth hormone (GH) and GH-releasing peptide-6 increase brain insulin-like growth factor-I expression and activate intracellular signaling pathways involved in neuroprotection. Endocrinology. 2002 Oct;143(10):4113-22. doi: 10.1210/en.2002-220261. PMID: 12239123. 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.
AHK-Cu (200mg)
AHK-Cu is a peptide composed of amino acids alanine, histidine, and lysine, with a copper ion coordinated by various parts of these three amino acids.(1) This peptide appears to be naturally present in the bloodstream and has been suggested as a potential element in regulating the growth, development, and apoptosis of vascular endothelial cells. AHK-Cu, also known as copper AHK, has been researched for its potential in hair growth and supporting skin tissue integrity. This peptide has been suggested to exhibit its potential primarily on fibroblasts, responsible for maintaining and growing the extracellular matrix (ECM) components surrounding the cells. Fibroblasts also appear to secrete various biological substances, including the Vascular Endothelial Growth Factor (VEGF), which is suggested to promote the formation of new blood vessels. The copper ion in AHK-Cu is suggested to be involved in enzyme activity related to collagen and elastin synthesis. These two proteins are critical components of the extracellular matrix and play a role in maintaining the skin tissues' structural integrity. Copper ions are also suggested to exhibit antioxidant properties. Chemical Makeup(2) Molecular Formula: C15H25CuN6O4 Molecular Weight: 416.9 g/mol Other known titles: ALA-HIS-LYS-CU, L-Alanyl-κN-L-histidyl-κN,κN3-L-lysinato(2-)]copper Monohydrochloride Research and Clinical Studies AHK-Cu Peptide and Antioxidative Potential AHK-Cu is posited to have potent antioxidant qualities, primarily due to its distinct amino acid structure. Based on the antioxidative properties of this peptide, studies have suggested its potential in amplifying hair follicle size, which may increase growth. This peptide has been the focus of numerous in-vitro investigations, particularly concerning its role in hair growth. These studies uniformly suggest AHK-Cu's potential to foster hair follicle development. In addition to hair growth, AHK-Cu's scope of application may extend to cell aging, wound healing, and other areas, according to researchers. They posit its potential role in boosting dermal cell multiplication and survival, both of which are essential in collagen production. Collagen is a vital element for maintaining skin cell turnover and function, and the increased cell activity provided by AHK-Cu may facilitate this process.(3) AHK-Cu Peptide and Hair Follicle Development Researchers posit that the tripeptide AHK-Cu may potentially stimulate the proliferation of dermal fibroblasts, a type of cell that produces substances like vascular endothelial growth factor (VEGF), which are considered to be crucial for the growth of blood vessels. AHK-Cu may also reduce the secretion of transforming growth factor-beta1 by dermal fibroblasts. In a recent study,(4) the potential of AHK-Cu on hair growth was investigated. It was suggested that the peptide may promote the elongation of hair follicles and the proliferation of dermal papilla cells (DPCs), which are specialized fibroblasts with a potential to increase the growth and development of hair follicles. Moreover, the authors suggested that the presence of AHK-Cu may have reduced the number of apoptotic dermal papilla cells. Further analysis suggested that the peptide may have increased the ratio of Bcl-2/Bax, and potentially decreased cleaved caspase-3 and PARP levels, two markers of cell death. The Bcl-2/Bax ratio is suggested to play a potential role in the regulation of apoptosis. Bcl-2 is posited as an anti-apoptotic protein that apparently inhibits cell death, while Bax is suggested to be a pro-apoptotic protein that promotes cell death. Thus, a higher Bcl-2/Bax ratio is posted as a predominance of Bcl-2, which may inhibit apoptosis and apparently promotes cell survival. Ultimately, the researchers suggested that AHK-Cu “stimulated the elongation of […] hair follicles […] and the proliferation of DPCs in vitro.” Based on these observations, the researchers commented, “The present study proposed that AHK-Cu promotes the growth of [...] hair follicles, and this stimulatory effect may occur due to stimulation of the proliferation and the preclusion of the apoptosis of DPCs.”(4). Other researchers delving into this trial also noticed that the peptide may have interacted with VEGF and Transforming Growth Factor Beta 1 (TGF-β1). TGF-β1 is researched for its role in cell proliferation, differentiation, and apoptosis. It is posited to be involved in several cellular processes, including the regulation of immune responses and wound healing. By potentially downregulating TGF-β1, AHK-Cu may alter these cellular processes, possibly affecting cell growth and the immune response at a cellular level. On the other hand VEGF is researched for its role in angiogenesis, the formation of new blood vessels from pre-existing vessels. The upregulation of VEGF by AHK-Cu might imply an enhanced potential for angiogenesis, which could influence nutrient and oxygen supply at the cellular level.(5) VEGF specifically is posited to foster the development of blood vessels surrounding hair follicles. This action potentially aids in delivering nutrients and oxygen to the hair follicles, thereby supporting hair growth. AHK-Cu Peptide and Alopecia Research The study examined the potential of two formulations containing growth factors and peptides such as vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-1, keratinocyte growth factor, and copper tripeptide 1 and related peptides such as AHK-Cu, suspended in a sterile vehicle. The experiment investigated the potential cytotoxicity of these factors using in vitro keratinocyte and fibroblast cell assays. The formulations were also investigated for their potential for hair growth and hair follicle viability in cases of secondary alopecia.(1) The authors suggested that both formulations appeared to produce a positive response regarding hair growth in the animals. The formulations also were posited to be impactful when tested alongside agents that may be associated with alopecia. Researchers Rinky Kapoor et al. state, “Results seem encouraging enough to warrant a trial in [...] secondary alopecia.” (1) AHK-Cu Peptide and Skin Tissue Integrity Preliminary lab studies have suggested that the core molecule of the peptide, AHK, may stimulate the growth of fibroblast cells and the production of collagen. Notably, AHK appears to improve the survival and multiplication of dermal fibroblasts, which are researched for their potential for generating vital skin proteins like collagen. In experiments with normal dermal fibroblasts, AHK was observed to apparently boost both cell growth and viability, alongside enhancing collagen type I production. This conclusion was drawn by measuring collagen type I levels produced by fibroblasts in a cell culture following exposure to varying concentrations of AHK. The studies indicated that AHK's presence may have raised collagen type I production, with a threefold increase compared to the control group. These results imply that AHK could potentially rejuvenate the extracellular matrix and contribute to skin function.(6) AHK-Cu peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References Kapoor R, Shome D, Vadera S, Kumar V, Ram MS. QR678 & QR678 Neo Hair Growth Formulations: A Cellular Toxicity & Animal Efficacy Study. Plast Reconstr Surg Glob Open. 2020 Aug 25;8(8):e2843. doi: 10.1097/GOX.0000000000002843. PMID: 32983753; PMCID: PMC7489598. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489598/ AHK-Cu, ChemBK. https://www.chembk.com/en/chem/AHK-Cu Kecel-Gunduza, S., Kocb, E., Bicaka, B., Kokcub, Y., Ozela, A. E., & Akyuzc, S. (2020). IN SILICO ANALYSIS FOR CHARACTERIZING THE STRUCTURE AND BINDING PROPERTIES OF ALA-HIS-LYS (AHK) TRIPEPTIDE. The Online Journal of Science and Technology-July, 10(3). Pyo HK, Yoo HG, Won CH, Lee SH, Kang YJ, Eun HC, Cho KH, Kim KH. The effect of tripeptide-copper complex on human hair growth in vitro. Arch Pharm Res. 2007 Jul;30(7):834-9. doi: 10.1007/BF02978833. PMID: 17703734. https://pubmed.ncbi.nlm.nih.gov/17703734/ Sadgrove NJ, Simmonds MSJ. Topical and nutricosmetic products for healthy hair and dermal anti-aging using "dual-acting" (2 for 1) plant-based peptides, hormones, and cannabinoids. FASEB Bioadv. 2021 Jun 6;3(8):601-610. doi: 10.1096/fba.2021-00022. PMID: 34377956; PMCID: PMC8332470. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8332470/ Patt, L. M., & Procyte, A. (2009). Neova® DNA Repair Factor Nourishing Lotion Stimulates Collagen and Speeds Natural Repair Process. skin, 1, 2. 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 & TB-500 Blend (10mg/20mg)
BPC-157 Peptide, also known as Pentadecapeptide BPC-157, or Body Protection Compound 157, is a wholly synthetic peptide that is potentially linked to multiple cellular functions and is perceived to have significance in healing of experimental models of injury. It is speculated to engage with cellular communication routes, possibly affecting elements associated with rejuvenation and recuperation. A few research studies hint that BPC-157 might also possess capabilities to encourage blood vessel formation and regulate inflammation-related activities.(1) Moreover, experimental findings have posited that BPC-157 may aid in safeguarding and regenerating various cells and tissues. Overall, BPC-157 has been suggested in various studies to potentially help with healing joint, tendon, and muscle tissue, as well as nerve tissue. TB-500 Peptide, also known as Synthetic thymosin beta-4, or TB-4, has been suggested by researchers to possibly assist in the healing process after injury, especially brain and neurological injury. Other TB-500 research has suggested it helps with wound healing and with hair growth. The peptide is a man-made variant of the thymosin beta-4 (Tβ4) peptide found naturally within the cells of the thymus organ, and encoded by the TMSB4X gene. From research on thymosin beta-4, TB-500 appears to modulate cell movement, differentiation, and tissue healing. It is believed to engage with various cellular signaling routes to manifest its actions. Investigations further imply that TB-500 might encourage angiogenesis, as well as cellular and tissue renewal.(2) Both BPC-157 and TB-500 are synthetic polypeptides, where TB-500 is composed of 43 amino acids, and BPC-157 is composed of 15 amino acids.(3)(4) Overview Based on Tβ4 research, TB-500 has been suggested to exert potential action on cellular motility via elevating the levels of actin proteins. More specifically it has been posited to regulate the cellular actin-cytoskeleton and cellular migration by sequestering G-actin. TB-500 has a distinct amino acid segment [(17)LKKTETQ(23)] which is hypothesized to be responsible for actin binding and potentially enhancing cellular motility. This in turn may exhibit positive action on wound healing processes.(5) TB-500 also seems to amplify the presence of microRNA-146a (miR-146a), which may act as a repressive regulator for certain cellular signaling routes such as those related to the activity of two inflammation-related cytokines called L-1 receptor-linked kinase 1 (IRAK1) and tumor necrosis factor receptor-linked factor 6 (TRAF6). This suggestion was further insisted as a potential mechanism of TB-500 by the authors of the research study, who also commented that "transfection of anti-miR-146a nucleotides reversed the inhibitory effect of Tβ4 on IRAK1 and TRAF6." Thus, TB-500 also appears to potentially work for healing by exerting anti-inflammatory action.(6) BPC-157 peptide has been suggested to exert some action via various processes encompassing nitric oxide production, control of cells pertinent to tissue restoration, growth elements, and inflammatory responses. It is conceivable that BPC-157 may exhibit some engagement with the NO mechanism, possibly providing a safeguard for the endothelium and perhaps encouraging angiogenic behaviors by fostering the development of new circulatory routes. Researchers suggest there is a chance it may boost the expression of the early growth response 1 gene, which may play a role in producing cytokines and growth stimuli, and possibly aid in the initial assembly of the extracellular framework, inclusive of collagen. It is worth highlighting that BPC-157's relation with nerve growth factor 1-A binding protein-2 may exert inhibitory action on specific elements.(7) As a result, new tissues composed of collagen may be formed, thereby possibly enhancing the healing of wounds more rapidly.(8) As both TB-500 and BPC-157 peptides appear to exhibit similar pharmacological potential, when blended together, the potential action of both may be maximized – what would otherwise occur with one peptide, might occur at a better, faster rate when combined. Chemical Makeup Molecular Formula: BPC-157: C62H98N16O22 TB-500: C212H350N56O78S Molecular Weight: BPC-157: 1419.5 g/mol TB-500: 4963 g/mol Other Known Titles BPC-157: Body Protection Compound-157 TB-500: Thymosin Beta-4 Research and Clinical Studies There are no research or clinical studies currently available where both TB-500 and BPC-157 were used in the same experiment or presented in combination, using the same test model. However, below listed are the studies observing the potential action of the individual peptides. BPC-157 & TB-500 Blend and Tissue Repair In one study with Tβ4 conducted in 1999,(9) experimentally wounded murine models were used as subjects, where half the number of murine models were presented with saline and the rest were presented with TB-500 peptide. The main aim of this study was to determine the potential tissue repair action of the peptide. Four days after the experiment, it was reported by the researchers that the murine models presented with TB-500 showed an apparent 41% increment in the re-epithelialization process (i.e., formation of new epithelial cells to resurface the wound). After seven days, the wounds presented with TB-500 had reportedly contracted by at least 11% as compared to the saline wounds. The authors commented that “these results suggest that Tβ4 is a potent wound healing factor with multiple activities...” In another 2006 clinical trial,(10) 72 test subjects with pressure ulcers were presented with TB-500. The main aim of this randomized, double blind study was to establish the potential of thymosin beta 4 (analogous to TB-500) in ulcer presence. The test subjects were divided into two groups, where one group was presented with placebo for 84 days and the rest were presented daily with various concentrations of the peptide, for up to 84 days. After 84 days, there was an occurrence of wound healing process where the ulcers reportedly exhibited signs of healing. In a BPC-157 study,(11) three experimental murine models were used as subjects where all were experimentally wounded, with either acute or chronic wounds. These murine models were then divided into two groups, where one was presented with a placebo compound and the other was presented with BC-157 peptide. After the experiment, all the murine models were histologically examined, and it was determined that the murine models with BPC-157 exhibited a prominently higher number of collagen and blood vessels formed as compared to the placebo murine models. BPC-157 & TB-500 Blend and Ligaments In one study,(12) the medial collateral ligament (MCL) of the murine models was transected (cut across) during surgery. All the murine models were then presented with a fibrin sealing agent, where some murine models were also presented with thymosin beta 4 (TB-500). Four weeks after the surgery, it was reported by the researchers that the healing tissues in the peptide murine models exhibited apparently evenly formed and spaced collagen cells. The collagen cells formed in the peptide murine models were reportedly wider as compared to the control murine models. Furthermore, the mechanical properties of the regenerating tissues, including the femur-medial collateral ligament-tibia complexes, appeared to be improved in the TB-500 group compared to the control. Another research article indicated that BPC-157 might play a role in aiding the recovery of connective tissues, potentially by promoting the growth of tendon explants. Interestingly, the study suggested that BPC-157 may possibly enhance the resilience of these cells in the face of oxidative stress. This outcome might be linked to the triggering of F-actin formation, as indicated by FITC-phalloidin staining. BPC-157 also appeared to enhance the in vitro movement of tendon fibroblasts as indicated by a transwell filter migration test. Furthermore, BPC-157 appeared to hasten the dispersion of tendon fibroblasts across culture plates. Additionally, the study delved into the possible role of the FAK-paxillin pathway (a pair of focal adhesion-linked proteins that relay signals following integrins) in conveying the action of BPC-157. Western blot tests hinted that the phosphorylation rates of both FAK and paxillin seemed to rise with BPC 157, yet the overall protein quantities stayed constant.(8) BPC-157 & TB-500 Blend and Muscle A study(13) was conducted on murine models with experimentally injured gastrocnemius muscle complex. These murine models were initially presented with corticosteroids, which reportedly contributed to severe muscular damage in these murine models . These murine models were then divided into two groups, where one was presented with placebo and the other with BPC-157 daily for up to 14 days. After the experiment, it was reported that the BPC-157 murine models appeared to exhibit complete restoration of their gastric muscles along with full ability to function. Whereas, the placebo treated group did not exhibit any apparent change to the damaged muscles. TB-500 may also have a potential effect on muscle cell regeneration, more specifically on cardiac muscle cells. One study suggests that TB-500 appears to bolster myocardial resilience in conditions of low oxygen, and seemingly fosters angiogenesis, possibly paving the way for cardiac cell repair. Researchers have hinted at a potential process where cardiac fibroblasts transition into cells resembling cardiomyocytes.(14) In the end, the scholars observed that TB-500, when combined with cardiac reprogramming techniques, might collaboratively reduce potential harm to cardiac cells and foster its regeneration by activating inherent cells within the cardiac region. An examination using murine models of coronary artery tying appeared to exhibit results which implied that TB-500 might elevate integrin-associated kinase (ILK) and protein kinase B operations in the heart, possibly boosting early cardiomyocyte endurance and seemingly enhancing heart performance.(15) The experts also suggested that TB-500 might support the movement of myocardial and endothelial cells in the fetal heart and maintains this capability in mature cardiomyocytes. BPC-157 & TB-500 Peptide Blend is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Seiwerth, S., Milavic, M., Vukojevic, J., Gojkovic, S., Krezic, I., Vuletic, L. B., Pavlov, K. H., Petrovic, A., Sikiric, S., Vranes, H., Prtoric, A., Zizek, H., Durasin, T., Dobric, I., Staresinic, M., Strbe, S., Knezevic, M., Sola, M., Kokot, A., Sever, M., … Sikiric, P. (2021). Stable Gastric Pentadecapeptide BPC 157 and Wound Healing. Frontiers in pharmacology, 12, 627533. https://doi.org/10.3389/fphar.2021.627533 Maar, K., Hetenyi, R., Maar, S., Faskerti, G., Hanna, D., Lippai, B., Takatsy, A., & Bock-Marquette, I. (2021). Utilizing Developmentally Essential Secreted Peptides Such as Thymosin Beta-4 to Remind the Adult Organs of Their Embryonic State-New Directions in Anti-Aging Regenerative Therapies. Cells, 10(6), 1343. https://doi.org/10.3390/cells10061343 National Center for Biotechnology Information. “PubChem Compound Summary for CID 132558700, CID 132558700” PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/132558700 National Center for Biotechnology Information. “PubChem Compound Summary for CID 9941957” PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Bpc-157 Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008 May 15;453(7193):314-21. doi: 10.1038/nature07039. PMID: 18480812. https://pubmed.ncbi.nlm.nih.gov/18480812/ Santra, M., Zhang, Z. G., Yang, J., Santra, S., Santra, S., Chopp, M., & Morris, D. C. (2014). Thymosin β4 up-regulation of microRNA-146a promotes oligodendrocyte differentiation and suppression of the Toll-like proinflammatory pathway. The Journal of biological chemistry, 289(28), 19508–19518. https://doi.org/10.1074/jbc.M113.529966 Sikiric, Predrag et al. “Brain-gut Axis and Pentadecapeptide BPC-157: Theoretical and Practical Implications.” Current neuropharmacology vol. 14,8 (2016): 857-865. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333585/#r1 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/ Katherine M. Malinda et.al, Thymosin β4 Accelerates Wound Healing, Journal of Investigative Dermatology, Volume 113, Issue 3, 1999, Pages 364-368, ISSN 0022-202X, https://www.sciencedirect.com/science/article/pii/S0022202X15405950 Study of Thymosin Beta 4 in Patients With Pressure Ulcers. https://www.clinicaltrials.gov/ct2/show/NCT00382174 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/ Xu B, Yang M, Li Z, Zhang Y, Jiang Z, Guan S, Jiang D. Thymosin β4 enhances the healing of medial collateral ligament injury in rat. Regul Pept. 2013 Jun 10;184:1-5. doi: 10.1016/j.regpep.2013.03.026. https://pubmed.ncbi.nlm.nih.gov/23523891/ 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/ Srivastava, D., Ieda, M., Fu, J., & Qian, L. (2012). Cardiac repair with thymosin β4 and cardiac reprogramming factors. Annals of the New York Academy of Sciences, 1270, 66–72. https://doi.org/10.1111/j.1749-6632.2012.06696.x Bock-Marquette, I., Saxena, A., White, M. D., Dimaio, J. M., & Srivastava, D. (2004). Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature, 432(7016), 466–472. https://doi.org/10.1038/nature03000 { "@context": "https:\/\/schema.org", "@type": "Product", "name": "BPC-157 & TB-500 Blend (10mg)", "description": "BPC-157 & TB-500 blend for sale online (10mg). Peptides for sale at 99% purity with top customer service. Read about research study results and information.", "image": "https://www.painandanxietymeds.shop/wp-content/uploads/2020/04/BPC-157-TB-500-5-5MG-300x300.jpg", "offers": [ { "@type": "Offer", "priceCurrency": "USD", "price": 105, "availability": "https:\/\/schema.org\/InStock", "itemCondition": "https:\/\/schema.org\/NewCondition", "seller": { "@type": "Organization", "name": "painandanxietymeds.shop" }, "url": "https:\/\/www.painandanxietymeds.shop\/bpc-157-tb-500-10mg-blend/", "hasMerchantReturnPolicy": { "@type": "MerchantReturnPolicy", "applicableCountry": "US", "returnPolicyCategory": "https:\/\/schema.org\/MerchantReturnNotPermitted" }, "shippingDetails": { "@type": "OfferShippingDetails", "shippingRate": { "@type": "MonetaryAmount", "minValue": 0, "maxValue": 9.25, "currency": "USD" }, "shippingDestination": { "@type": "DefinedRegion", "addressCountry": "US" }, "deliveryTime": { "@type": "ShippingDeliveryTime", "handlingTime": { "@type": "QuantitativeValue", "minValue": 1, "maxValue": 2, "unitCode": "d" }, "transitTime": { "@type": "QuantitativeValue", "minValue": 1, "maxValue": 5, "unitCode": "d" } } }, "priceValidUntil": "2027-04-09T15:10:59+00:00" } ], "url": "https:\/\/www.painandanxietymeds.shop\/bpc-157-tb-500-10mg-blend/", "aggregateRating": { "@type": "AggregateRating", "ratingValue": 98, "bestRating": 100, "reviewCount": 732 }, "review": [] } 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 (5mg)
Fragment 176-191 peptide, also known as hGH Fragment 176-191, tyr-hGH 177-191, or AOD-9604, has been suggested by researchers that it may stimulate weight loss and fat burn in a fashion similar to that of the growth hormone (hGH). hGH is a naturally occurring hormone, which, apart from stimulating growth, as the name suggests, may also stimulate catabolism of adipose tissue and the release of lipids from fat cells. Fragment 176-191 is a small ‘fragment’ of the growth hormone hGH composed of 16 amino acids. This involves the last 16 amino acids of the hGH molecule, which scientists propose to be the “lipolytic fragment” of hGH. Lipolythic, as a term, reflects the purported fat-burning properties of the molecule. To potentially improve the stability of the peptide, the first amino acid in the hGH Fragment 176-191 sequence is also replaced by tyrosine. Thus, the peptide is also labeled as Fragment tyr-hGH 177-191.(1)(2) Overview This peptide could, in theory, aim at the beta-3 adrenergic receptors (ß3-AR), which might, in turn, lead to a potential weight loss action. It is posited that through these receptors, the peptide may encourage fat burning in adipose tissue and foster 'thermogenesis' in skeletal muscle cells. In a study involving obese murine models exposed to the peptide for two weeks, there seemed to be an apparent decrease in weight, including a reduction in excess fat. These observations are thought to be linked to a rise in the activity of lipolytic beta-3 adrenergic receptors, hinting that the peptide's actions could be connected to the beta-adrenergic pathway. The researchers commented that Fragment 176-191 may be “capable of increasing the repressed levels of beta(3)-AR RNA in obese mice to levels comparable with those in lean mice.” Unfortunately, the data may not be conclusive, as the research on murine models with disabled lipolytic receptors suggested that the peptide still led to apparent weight loss, suggesting its actions might not solely rely on these receptors. Thus, it was also considered that the peptide might help burn fat through mechanisms like energy expenditure and fat oxidation, though this remains an area for further investigation.(3) As mentioned, the presence of tyrosine at the N-terminus of the fragment increases the stability of the peptide. In addition, there appears to be a naturally occurring disulfide bridge between the two cysteine amino acids in the molecule of hGH and hGH Fragment 176-191. This bridge appears to further stabilize the molecule and may increase its resistance against degradation in various environments, including stomach acid.(4)(5) Chemical Makeup Molecular Formula: C78H125N23O23S2 Molecular Weight: 1817.12 g/mol Other Known Titles: hGH Fragment 176-191; Lipolytic fragment Research and Clinical Studies Fragment 176-191 and Fat Cells As mentioned, Fragment 176-191 is believed to potentially increase fat burning through different mechanisms, which may include the upregulation of the beta-3 adrenergic receptors. More specifically, the peptide might elevate the expression levels of beta(3)-AR RNA in fat cells. This suggests that Fragment 176-191 may influence signaling pathways or transcription factors that enhance the production of beta-3 adrenergic receptor mRNA, leading to increased synthesis of the beta-3 adrenergic receptors protein. With more beta-3 adrenergic receptors present on the surface of adipocytes (fat cells), the cells may become more sensitive to lipolytic signals. This posits that even though Fragment 176-191 may not directly activate beta-3 adrenergic receptors, the increased number of receptors might amplify the natural lipolytic response to endogenous catecholamines (like adrenaline), which are suggested to engage these receptors directly. Fragment 176-191 might also activate other cellular signaling mechanisms that indirectly boost fat burning. For example, it may influence pathways that either upregulate the expression of enzymes involved in the lipolysis process or enhance the cellular response to lipolytic signals by modulating the activity of secondary messengers within the cell. This has been explored by clinical trials, the most notable of which was METAOD005. This trial was initiated to explore the possible fat-burning action of a peptide. 300 test subjects were involved in this investigation, which lasted 12 weeks. There were six groups, including one control group and five Fragment 176-191 groups. It was suggested that one of the Fragment 176-191 groups experienced an apparent decrease in body weight, potentially by around 5.7 pounds. Moreover, it was posited that the peptide may have possibly contributed to improvements in the cholesterol levels and glucose tolerance of these participants.(6) Fragment 176-191 and Cartilage Regeneration Some researchers have posited that Fragment 176-191 peptide may have some of the proposed regenerative properties of hGH, in addition to its apparent fat-burning potential. To explore these potential impacts of Fragment 176-191 peptide, researchers used a knee osteoarthritis model caused by collagenase. The experimental models were introduced with type II collagenase to apparently induce damage to the knee cartilage. Following this, for a period of 4-7 weeks, the models were split into four groups including saline (Group 1), hyaluronic acid (Group 2), Fragment 176-191 peptide (Group 3), and a combination of Fragment 176-191 peptide with hyaluronic acid (Group 4). The severity of the cartilage damage was evaluated through both morphological and histopathological analysis, and the degree of lameness was observed 8 weeks after the beginning of the trial. The researchers commented, "Mean gross morphological and histopathological scores were significantly higher in Group 1 than in Groups 2, 3, and 4, and the scores were significantly lower in Group 4 than in Groups 2 and 3. The lameness period in Group 4 was significantly shorter than those in Groups 1, 2, and 3.” This suggested that both hyaluronic acid and Fragment 176-191 peptide may be better than saline in stimulating an apparent cartilage regeneration, and the best research outcome may be achieved with a combination of Fragment 176-191 peptide and hyaluronic acid.(7) Fragment 176-191 and Hyperglycemia In one study,(8) several synthetic hGH peptides, including Fragment 176-191, were presented in normal functioning murine models to determine its potential on glycogen metabolism. Upon delivery, it was reported that the peptide appeared to induce a slight increment in levels of blood glucose and lactate, with a slight reduction in the ratio of glycogen synthase in muscle, adipose tissues, and the liver. It was suggested that this outcome was due to the peptide's apparent action of converting the enzymes from their active state to inactive state, as the total synthase levels appeared to remain at constant concentrations. Fragment 176-191 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Cox HD, Smeal SJ, Hughes CM, Cox JE, Eichner D. Detection and in vitro metabolism of AOD9604. Drug Test Anal. 2015 Jan;7(1):31-8. doi: 10.1002/dta.1715. Epub 2014 Sep 10. PMID: 25208511. Heffernan, Mark, et al. "The Effects of Human GH and Its Lipolytic Fragment (AOD9604) on Lipid Metabolism Following Chronic Treatment in Obese Mice andβ 3-AR Knock-Out Mice." Endocrinology 142.12 (2001): 5182-5189. 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. Stier, Heike, Evert Vos, and David Kenley. "Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans." Journal of Endocrinology and Metabolism 3.1-2 (2013): 7-15. Moré, Margret I., and David Kenley. "Safety and metabolism of AOD9604, a novel nutraceutical ingredient for improved metabolic health." Journal of Endocrinology and Metabolism 4.3 (2014): 64-77. Valentino, M A et al. “Central and peripheral molecular targets for antiobesity pharmacotherapy.” Clinical pharmacology and therapeutics vol. 87,6 (2010): 652-62. doi: 10.1038/clpt.2010.57 Kwon, Dong Rak, and Gi Young Park. “Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model.” Annals of clinical and laboratory science vol. 45,4 (2015): 426-32. Ma GY, Macaulay SL, Maggs JA, Armstrong JM, Bornstein J. The mechanism of the hyperglycaemic action of synthetic peptides related to the C-terminal sequence of human growth hormone. Biochim Biophys Acta. 1982 Jun 16;716(3):400-9. doi: 10.1016/0304-4165(82)90033-2. PMID: 6810951. 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.
Nonapeptide-1 (200mg)
Nonapeptide-1 is a nine amino acid peptide that was first developed in the 1990s, sparking research interest due to its potential to inhibit the synthesis of melanin, the main pigment in mammals responsible for color in the skin, fur, hair, eyes, etc. The research on Nonapeptide-1 is still in its early stages, and much is still unknown about its potential and mechanisms of action. Studies on Nonapeptide-1 have primarily focused on its potential to inhibit melanin production by interfering with the signaling pathway involved in melanogenesis. Specifically, Nonapeptide-1 is thought by researchers to possibly inhibit the melanocortin-1 receptors, which may prevent the action of melanocyte-stimulating hormones and the activation of the enzyme tyrosinase, which is necessary for the synthesis of melanin.(1) By doing so, Nonapeptide-1 may have a reducing potential on hyperpigmentation and skin tone in animal studies. Nevertheless, further studies are needed to fully understand the potential of this peptide. Chemical Makeup Molecular formula: C61H87N15O9S Molecular weight: 1206.5 g/mol Research and Clinical Studies Nonapeptide-1 Discovery and Mechanism of Action Scientists have investigated a peptide library of 31,360 structurally different melanocortin-1 receptor antagonists with the aim of finding the most potentially potent inhibitor of these receptors.(2) These melanocortin-1 receptors may be found in melanocytes, which are pigment-producing cells. One of the main agonists of these receptors is considered to be the alpha-melanocyte-stimulating hormone (α-MSH). α-MSH is a neuropeptide thought to be involved in regulating pigmentation, energy homeostasis, and immune function. The pituitary gland and the skin produce it. α-MSH may stimulate melanin production by binding to the melanocortin-1 receptor on melanocytes and activating a signaling cascade that increases tyrosinase activity and melanin production. Tyrosinase is the rate-limiting enzyme in melanogenesis.(3) In addition, α-MSH may also act as an antagonist for the agouti signaling protein (ASP), which inhibits MC1R activity and reduces melanin production. The researchers suggested that the most potent antagonist of all 31,360 peptides was Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH2, aka nonapeptide-1.(2) The scientists reported that it "has an IC50 value of 11 +/- 7 nM'' and the "analysis revealed that D-Trp5 and Phe6 were crucial to its antagonistic properties which could be potentiated by D-Phe3." Nonapeptide-1 and Skin Pigmentation The potential action of Nonapeptide-1 has been researched in both clinical and laboratory settings. In one in vitro study, keratinocyte cell line (HaCaT) cells and epidermal melanocytes (HEM) were exposed to UVA and imbued with different concentrations of the acetate salt of Nonapeptide-1.(4) The scientists accessed cell viability, melanin content, and tyrosinase activity. The scientists suggested that Nonapeptide-1 downregulated melanocortin 1 receptor expression without affecting α-MSH levels, and might significantly decrease the expression of tyrosinase, TRP1 (tyrosinase-related protein-1), TRP2 (tyrosinase-related protein-2), and MITF (microphthalmia-associated transcription factor) with or without concomitant UVA radiation. Besides, the researchers further posited that cells infused with nonapeptide-1 may significantly increase the ability to resist melanin production. More recent research on nonapeptide-1 also hypothesizes that the peptide may produce an apparent skin lightening by at least 33% and suggested a continued improvement over time.(5) The only clinical trial on the topic was a prospective double-blinded parallel-group randomized controlled pilot study that lasted eight months and had three phases.(6) The researchers reported an apparent improvement in severity scores of melasma and mean melanin index. They also commented, "The melasma area and severity index score showed a consistent reduction in the case group, whereas it increased in the control group from baseline." Nonapeptide-1 and Future Research Potential Apart from melanocytes, the melanocortin 1 receptors that Nonapeptide-1 potentially inhibits may be expressed in other cells, such as nerve cells and immune cells. More specifically, the melanocortin 1 receptors may be found in the periaqueductal gray matter, which plays a major role in nociception.(7) Scientists have conducted experiments on mice with overexpression of an endogenous antagonist of the melanocortin 1 receptor compared to control mice.(8) They tested their response to painful and non-painful stimuli and their response to inflammatory and neuropathic pain. Additionally, they tested their aversion to capsaicin, which may activate the TRPV1 noxious heat receptor, using a paired preference paradigm. The scientists indicated that mice overexpressing the melanocortin 1 receptor antagonist exhibited an apparently reduced inflammatory pain response and a slower onset of inflammation-induced hypersensitivity and allodynia. They were also observed to exhibit a decreased aversion to moderate concentrations of capsaicin. The scientists highlighted that these results occurred only in female mice and that "mice of either sex did not show any effect of mutant genotype on neuropathic pain." Studies also suggest that melanocortin 1 receptors may play a role in the growth and survival of melanoma tumor cells.(9) Melanoma is a type of skin cancer with a high mortality rate, and mutations in the melanocortin 1 receptor gene may be associated with changes in the risk of developing melanoma. In this study, the researchers inhibited melanocortin 1 receptors using natural inhibitors, which reduced melanin synthesis and morphological heterogeneity in murine B16-F10 melanoma cells. They found that the inhibition resulted in slower tumor cell growth and a more homogeneous size and morphology of the tumors. The study suggests that melanocortin 1 receptors may play an important role in regulating melanoma growth and morphology, and persistent inhibition of melanocortin 1 receptors may significantly slow the growth rate of the tumor cells that express these receptors. Nonapeptide-1 hasn't been researched regarding its potential impact on melanoma tumor cells. Nonapeptide-1 is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Dhatt S (2006) Rebuilding the dermal matrix with this new in-demand ingredient in skin care products. Aesthetic Trends Technol 17–20 Jayawickreme, C. K., Quillan, J. M., Graminski, G. F., & Lerner, M. R. (1994). Discovery and structure-function analysis of alpha-melanocyte-stimulating hormone antagonists. Journal of Biological Chemistry, 269(47), 29846-29854. Gaston, L. S., & Majzoub, J. A. (2022). Adrenocorticotrophin. In The Pituitary (pp. 51-89). Content Repository Only!. Chen, J., Li, H., Liang, B., & Zhu, H. (2022). Effects of tea polyphenols on UVA-induced melanogenesis via inhibition of α-MSH-MC1R signalling pathway. Postepy dermatologii i alergologii, 39(2), 327–335. https://doi.org/10.5114/ada.2022.115890 Mohammed, Y. H., Moghimi, H. R., Yousef, S. A., Chandrasekaran, N. C., Bibi, C. R., Sukumar, S. C., Grice, J. E., Sakran, W., & Roberts, M. S. (2017). Efficacy, Safety and Targets in Transdermal Active and Excipient Delivery. Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin: Methodology and General Considerations, 369–391. https://doi.org/10.1007/978-3-662-53270-6_23 Chatterjee, M., Neema, S., & Rajput, G. R. (2021). A randomized controlled pilot study of a proprietary combination versus sunscreen in melasma maintenance. Indian journal of dermatology, venereology and leprology, 88(1), 51–58. https://doi.org/10.25259/IJDVL_976_18 Xia, Y., Wikberg, J. E., & Chhajlani, V. (1995). Expression of melanocortin 1 receptor in periaqueductal gray matter. Neuroreport, 6(16), 2193-2196. Delaney, A., Keighren, M., Fleetwood-Walker, S. M., & Jackson, I. J. (2010). Involvement of the melanocortin-1 receptor in acute pain and pain of inflammatory but not neuropathic origin. PloS one, 5(9), e12498. https://doi.org/10.1371/journal.pone.0012498 Kansal, R. G., McCravy, M. S., Basham, J. H., Earl, J. A., McMurray, S. L., Starner, C. J., Whitt, M. A., & Albritton, L. M. (2016). Inhibition of melanocortin 1 receptor slows melanoma growth, reduces tumor heterogeneity and increases survival. Oncotarget, 7(18), 26331–26345. https://doi.org/10.18632/oncotarget.8372 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.
Thymalin (25mg)
Thymalin is a polypeptide isolated from the thymus gland, believed by researchers to help regulate immune functions.(2) Studies have suggested that Thymalin, a naturally occurring polypeptide, is primarily found in the young epidermal cells of the thymus gland. With increasing age, the levels of Thymalin decrease, eventually becoming thinned out and non-uniform in nature.(5) Natural thymic peptides such as Thymalin were first isolated from the thymus gland via a mild acid extraction process. Upon further isolation studies, the proposed immunomodulatory molecule composed by Thymalin (L-Glu-L-Trp) was discovered and researched. This dipeptide molecule in Thymalin may possibly play a role in the peptide mechanism.(4) While both Thymalin and Thymulin are naturally occurring thymic factors, their mode of action is hypothesized by researchers to different, where Thymalin is a polypeptide that may regulate thymic functions at optimal levels, the Thymulin appears to be a zinc-dependent nonapeptide hormone that may possibly enhance the thymic functions in fighting T-cell suppression. Overview Studies have been conducted to understand the functioning of both natural and synthetic thymic peptides.(6) The main compounds that have been studied areThymalin (natural polypeptide), Thymogen (synthetic peptide) and Vilon (its derived dipeptide). The study suggested that all the peptides within this thymic family appear to function via possibly stimulating thymic functions i.e., differentiation of T-cells, induced changes in the nucleotides and cytokine cells and secretion of lymphocytes. The other significant hypothesis made during this study was that the naturally occurring peptide, Thymalin, may potentially stimulate the antioxidant responses, whereas the two synthetic analogues did not appear to the researchers to alter these responses. Thymalin, being a natural extract, possibly exhibits a broader range of biological activities compared to its synthetic counterparts, Thymogen and Vilon. For instance, by potentially aiding in the reduction of oxidative stress, Thymalin might contribute indirectly to controlling inflammatory responses, which are typically exacerbated by oxidative damage. Chemical Makeup Molecular Formula: C33H54N12O15 Molecular Weight: 858.864 g/mol Other Known Titles: Thymulin, Thymic Factor Research and Clinical Studies Thymalin and Carcinogenesis In this study,(7) 76 female rats of 5 months of age were selected. The main aim of this study was to determine the potential of Thymalin on the tumor development and thereby survival rates of the test models. The rats were divided into two groups, where 32 rats were presented with saline, and the remaining rats were presented with Thymalin. The compounds were introduced to the test subjects 5x a week for one year. All rats were monitored for mortality rates and development of tumors throughout the one-year period. The study results reported that the average lifespan in the control group was 949 days whereas in the peptide group was 1048 days. The "aging rate" was reported as 0.0071 days in the control group and 0.0041 in the peptide group. What's more, the tumor incidence reportedly decreased by 1.5x in the peptide group as compared to the control group. It is plausible that the reduction in tumor occurrence was even more significant for hematopoietic cancer cells, with incidences appearing to be approximately 3.4 times lower in murine models exposed to the peptide. This observation might indicate that the peptide could influence key elements of the immune system essential for inhibiting cancer cell development and its progression. Subsequent inquiries into the mechanisms underlying these observations might show that the L-Glu-L-Trp in Thymalin is linked with improved differentiation of T-cumin, which are critical components of the adaptive immune system. This process may enhance the ability of these cells to identify complexes of peptides and major histocompatibility complex (MHC) molecules. Furthermore, noticeable alterations were observed in the levels of cyclic nucleotides within the cells, which play roles in cellular signaling processes. Additionally, there was an activation of neutrophil chemotaxis and phagocytosis, processes involved in the first-line defense against pathogens and potentially malignant cells. Furthermore, analysis of the study's data demonstrated that L-Glu-L-Trp was quickly absorbed, attaining notable concentrations in tissues such as the liver and lymph nodes. The presence of the peptide in these pivotal locations might enable a more efficient immune response, which could be a factor in the observed scientific findings. Thymalin and Viral Infection In this clinical study,(8) 50 female test subjects with HHV 1 and a group of control subjects were examined. All the subjects were presented with thymic peptides similar to Thymalin for a period of 2 months. Before and after the study, peripheral blood cell tissues were collected from the subjects and examined to monitor the cytokine levels upon peptide presentation. Upon analysis, it was determined that compared to the control group, the cytokine levels were elevated in a higher proportion in the HHV 1 group. The levels of cytokines CD4+ and CD8+ were reportedly elevated in the HHV 1 group as compared to the control. Additionally, researchers reported that after a two-month period, no reactivation of the HHV 1 virus was reported in the test group. Further analysis was conducted to understand the potential mechanisms through which thymic peptides may influence immune exhaustion markers and cytokine levels. The study reported changes in the expression of the exhaustion markers PD-1 and PD-L1 on both T and B lymphocytes. Post-exposure measurements indicated a notable decrease in the co-expression of these markers, suggesting a potential revitalization of immune response capabilities in the subjects. Moreover, the specific increase in the levels of IFN-γ and IL-2 related to thymic peptides suggests a targeted enhancement of Th1 immune responses, which are crucial for antiviral defense. This action was observed without significant changes in the levels of IL-4 and IL-10, indicating that thymic peptides might selectively promote a type of immune response that is more effective against viral infections, without broadly elevating all aspects of immune activation. Thymalin and Toxic Goiter Models In this clinical study,(9) 104 test subjects with mild Diffuse Toxic Goiter (DTG) were enrolled, and their levels of medium weight molecular peptides and lipid oxidation rates were monitored. The main aim of this study was to establish the potential of Thymalin in interacting with DTG. The test subjects were divided into five groups where each group was presented with an external compound, a combination of Thymalin and an external compound, or the peptide alone. Following the study, it was reported that a combination of compounds and Thymalin exhibited mitigation of DTG symptoms in the test subjects. Thymalin and Lympholeukemia Models In this clinical study,(12) test subjects with chronic lymphoid leukemia were enrolled in the inclusion study composed of specific and nonspecific immune correction action, namely Thymalin presentation and plasmapheresis, respectively. Compared to the sole impact of chemotherapeutic agents, this combined presentation apparently resulted in a reported increase in physiological functioning within a short period. Thymalin and Geroprotection In this test study,(13) the geroprotective potential of Thymalin (thymic peptide) and Epithalamin (pineal peptide) were studied on 266 mature test subjects for a period of 6 to 8 years. The subjects were presented with the peptides for the first 2 to 3 years and were then monitored on a regular basis. The subjects were divided into several groups: Group I was presented with Thymalin, Group II with Epithalamin, Group III with both peptides and a separate group where test subjects were presented with both peptides at a different concentration rate. The peptides were presented to the test models annually for 6 years. The studies suggested that basic functions improved significantly upon study under both the peptides, including cardiovascular, neurological, immunological functions and that the peptide possibly improved rates of metabolism and hemostasis. It is posited that Thymalin may contribute to the maintenance or possibly the rejuvenation of thymic function, which typically declines gradually. This action on thymic function might explain the observed improvements in T-cell mediated immunity. Researchers noted a potential restoration of both the quantity and functionality of T-cells, which are critical for adaptive immunity. Additionally, Thymalin may exert actions on systemic inflammation, a common feature in aging models. The study hinted at a possible reduction in markers of systemic inflammation in subjects exposed to Thymalin. This observation aligns with the hypothesized role of Thymalin in modulating cytokine production and immune cell regulation, which may collectively contribute to a reduction in chronic inflammation. The potential influence of Thymalin on stress hormones, particularly cortisol, was another focal point of the study. Thymalin might potentially modulate the hypothalamic-pituitary-adrenal (HPA) axis to stabilize cortisol levels, thereby mitigating some of the adverse actions of stress. In terms of metabolic actions, subjects exposed to Thymalin showed potential improvements in metabolic stability. Researchers observed a possible normalization of metabolic parameters such as glucose and lipid profiles. These changes could be indicative of Thymalin's influence on metabolic processes, possibly through enhancement of cellular metabolism or through direct actions on metabolic enzymes. Thymalin peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Disorders of the Immune system. https://www.hopkinsmedicine.org/health/conditions-and-diseases/disorders-of-the-immune-system Khavinson VK, Linkova NS, Kvetnoy IM, Polyakova VO, Drobintseva AO, Kvetnaia TV, Ivko OM. Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells. Bull Exp Biol Med. 2020 Nov;170(1):118-122. doi: 10.1007/s10517-020-05016-z. Epub 2020 Nov 25. https://pubmed.ncbi.nlm.nih.gov/33237528/ Remien K, Jan A. Anatomy, Head and Neck, Thymus. [Updated 2021 Feb 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK539748/ Morozov VG, Khavinson VK. Natural and synthetic thymic peptides as therapeutics for immune dysfunction. Int J Immunopharmacol. 1997 Sep-Oct;19(9-10):501-5. doi: 10.1016/s0192-0561(97)00058-1. https://pubmed.ncbi.nlm.nih.gov/9637345/ Khlystova, Z.S., Kalinina, I.I., Shmeleva, S.P. et al. Age-Related Changes of Thymalin Content in Human Epidermis. Bulletin of Experimental Biology and Medicine 133, 620–622 (2002). https://doi.org/10.1023/A:1020214816056 V.G. Morozov, V.Kh. Khavinson, Natural and synthetic thymic peptides as therapeutics for immune dysfunction, International Journal of Immunopharmacology, Volume 19, Issues 9–10, 1997, Pages 501-505. https://www.sciencedirect.com/science/article/abs/pii/S0192056197000581 Anisimov VN, Khavinson VK, Morozov VG. Immunomodulatory synthetic dipeptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats. Biogerontology. 2000;1(1):55-9. https://pubmed.ncbi.nlm.nih.gov/11707921/ Hymos A, Grywalska E, Klatka J, Klatka M, Korona-Głowniak I, Roliński J. ThymicPeptides Reverse Immune Exhaustion in Patients with Reactivated Human Alphaherpesvirus1 Infections. Int J Mol Sci. 2020 Mar 30;21(7):2379. https://pubmed.ncbi.nlm.nih.gov/32235584/ Iangolenko VV. The effect of combined therapy with the use of thymalin and piracetam on the level of middle-molecule peptides in the blood and on the lipid peroxidation activity in patients with diffuse toxic goiter. Ter Arkh. 1991;63(10):60-3. Russian. https://pubmed.ncbi.nlm.nih.gov/1725225/ Khavinson, V., Linkova, N., Dyatlova, A., Kuznik, B., & Umnov, R. (2020). Peptides: Prospects for Use in the Treatment of COVID-19. Molecules (Basel, Switzerland), 25(19), 4389. https://doi.org/10.3390/molecules25194389 Khavinson, V. K., Linkova, N. S., Kvetnoy, I. M., Polyakova, V. O., Drobintseva, A. O., Kvetnaia, T. V., & Ivko, O. M. (2020). Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells. Bulletin of experimental biology and medicine, 170(1), 118–122. https://doi.org/10.1007/s10517-020-05016-z Tretiak NN, Babenko TF, Gaĭdukova SN, Zverkova AS, The efficacy of using thymalin and plasmapheresis in the combined treatment of patients with chronic lympholeukemia. Lik Sprava. 1998 Mar-Apr;(2):93-6. Russian. https://pubmed.ncbi.nlm.nih.gov/9670669/ Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuro Endocrinol Lett. 2003 Jun-Aug;24(3-4):233-40. PMID: 14523363. https://pubmed.ncbi.nlm.nih.gov/14523363/ Hermánek J, Prokopic J. Influence of thymic preparations on the result of experimental infection with Taenia crassiceps (Zeder, 1800) in ICR mice. Folia Parasitol (Praha). 1989;36(4):331-40. https://pubmed.ncbi.nlm.nih.gov/2488049/ Bach JF, Dardenne M. Thymulin, a zinc-dependent hormone. Med Oncol Tumor Pharmacother. 1989;6(1):25-9. doi: 10.1007/BF02985220. PMID: 2657247. https://pubmed.ncbi.nlm.nih.gov/2657247/ National Center for Biotechnology Information. "PubChem Compound Summary for CID 3085284, Nonathymulin" PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Nonathymulin 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.