Peptides
Fragment 176-191 & Mod GRF 1-29 & Ipamorelin Blend (12mg)
Modified GRF 1-29 is a truncated version of Growth Hormone-Releasing Hormone (GHRH). Unlike GHRH, Mod GRF 1-29 is not a full-length peptide but rather a shorter version containing only 29 amino acids. In Mod GRF 1-29, four of the original amino acids have been modified, to enhance its stability. These modifications serve to make the molecule more resistant to degradation by dipeptidyl peptidase-4 (DPP-4) enzymes, which would otherwise break down the peptide structure. By reducing susceptibility to enzymatic degradation, these modifications may potentially increase the peptide's half-life and improve its pharmacokinetics.(1) Ipamorelin is a synthetic pentapeptide, falling under the growth hormone secretagogue receptor (GHSR) agonist category. The peptide was derived from GHRP-1, which in turn is an analog of met-enkephalin, but potentially may not possess affinity to the opioid receptors. It appears to activate the ghrelin receptors (GHSR) which appear to trigger growth hormone synthesis. Fragment 176-191, as the name implies, is a small ‘fragment’ of the growth hormone (hGH), also referred to as the “fat-burning peptide” for its potential in that area.(2) Fragment 176-191 peptide, composed of 16 amino acids, including the last 15 amino acids from 177 to 191 found in hGH, has tyrosine added at the N-terminus (beginning). The peptide is also known as AOD 9604.(3) Chemical Makeup(1)(3)(4) Molecular formula Fragment 176-191: C78H125N23O23S2 Modified GRF 1-29: C152H252N44O42 Ipamorelin: C38H49N9O5 Molecular weight Fragment 176-191: 1817.12 g/mol Modified GRF 1-29: 3367.9 g/mol Ipamorelin: 711.8 g/mol Other known titles Modified GRF 1-29: Mod GRF 1-29, CJC-1295 without DAC Ipamorelin Ipamorelin Acetate, IPA Fragment 176-191: AOD 9604, GH (hGH) lipolytic fragment, Somatostatin (177-191), tyrosyl Research and Clinical Studies Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and Lipolytic Action The peptide in the blend that is believed to possess the most potent lipolytic (fat-breaking) action is likely Fragment 176-191. In one study,(2) obese experimental murine models were subjected to the peptide for two consecutive weeks. After the completion of the study, it was noted that there appeared to be a significant reduction in the body weight of these murine models, including a reduction of excess body lipids. These results were deemed correlated to the increased concentration of the lipolytic ß3-AR receptors, indicating the peptides may work via the beta-adrenergic pathway. Further studies were conducted on the experimental mice with knocked-out lipolytic receptors. The peptide mice were reported to have experienced considerable weight loss, suggesting that the peptide may not depend on the lipolytic receptors to exert any action. Instead, it may possibly produce some fat-burning action via energy expenditure and fat oxidation. As per M Heffernan and his team, “this study demonstrates that the lipolytic actions of both hGH and AOD9604 are not mediated directly through the beta(3)-AR although both compounds increase beta(3)-AR expression, which may subsequently contribute to enhanced lipolytic sensitivity.” (2) Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and the Pituitary Gland One review of the available literature(5) suggested that these peptides appeared to yield various physiological changes, including “increase lean body mass, reduce fat mass, increase exercise tolerance and maximum oxygen uptake, enhance muscle strength, and improve linear growth…” in obese test models.(5) While Fragment 176-191 was suggested to exert its potential action for weight loss via peripheral mechanisms, the aforementioned observation in the review are related to the apparent central action of peptides like Mod GRF 1-29 and Ipamorelin on the pituitary gland. For example, Ipamorelin appears to work by potentially binding to the GHS-R1a receptor, also known as the growth hormone secretagogue receptor type 1a, which is found in the pituitary gland and the hypothalamus. Upon binding, this receptor activation may trigger a series of intracellular events that potentially culminate in the release of stored growth hormone from somatotroph cells (GH-producing cells) in the anterior pituitary. The apparent activation of the GHS-R1a receptor by Ipamorelin may lead to increased intracellular calcium ions through the phospholipase C pathway. The elevated calcium levels may prompt the secretory vesicles inside somatotropic cells to release growth hormone. On the other hand, Mod GRF 1-29 appears to interact with the GHRH receptors on somatotrophs in the anterior pituitary gland. Upon binding to the GHRH receptors, Mod GRF 1-29 appears to instigate a cascade of intracellular signaling events. One of the key pathways activated appears to be the adenylyl cyclase pathway. Activation of this pathway may result in the conversion of ATP (adenosine triphosphate) into cAMP (cyclic adenosine monophosphate). This rise in cAMP appears to activate protein kinase A (PKA), which then may lead to the phosphorylation of various proteins, including voltage-dependent calcium channels on the cell membrane. The subsequent opening of these calcium channels potentially facilitates the influx of calcium ions into the somatotropic cells. Elevated intracellular calcium concentrations, in turn, appear to prompt the secretory vesicles inside these cells to release growth hormone into the bloodstream. It is posited that through this series of intracellular events that Mod GRF 1-29, upon binding to GHRH receptors, the peptide might facilitate the release and synthesis of growth hormone. The combination of Mod GRF 1-29 with certain growth hormone-releasing peptides like Ipamorelin, may potentially lead to a synergistic action, apparently amplifying the release of growth hormone. Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and Fat Burning In 2004, a clinical trial(6) was launched, consisting of 300 obese test subjects. All these subjects were presented with the Fragment 176-191 peptide for 12 consecutive weeks. All subjects were divided into 6 groups – one group was presented with saline placebo, and the rest were given different peptide concentrations. After 12 weeks, when the subjects were examined, the group presented with the minor concentration appeared to exhibit the highest reduction in subject body weight (up to an average of 2.8 kilograms). Moreover, the trial also suggested that the peptide may have helped to improve these candidates’ cholesterol profiles and glucose tolerance levels. As per Chris Belyea, “The evidence from the trial is that over 12 weeks AOD9604 induces competitive weight loss with accompanying health benefits at a low dose and has superior tolerability.” (6) Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend, and Regeneration In one 2015 study,(7) 32 experimental rabbits were enrolled and divided into four groups of eight. All four groups were presented with placebo, Fragment 176-191 peptide, hyaluronic acid, or a combination of the peptide and hyaluronic acid. This study was conducted for approximately 7 weeks. After the completion of the study, all rabbits were examined for cartilage damage. Among all groups, the rabbits presented with the peptide and hyaluronic acid combination appeared to exhibit minor cartilage degeneration. The report concluded that “Intra-articular AOD9604 [administration] using ultrasound guidance enhanced cartilage regeneration, and combined AOD9604 and HA [administration] were more effective than HA or AOD9604 [doses] alone in the collagenase-induced knee OA rabbit model.” (7) Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend and Bone Mineralization Considering the different peptides in the blend, Ipamorelin appears to be the one with a potential for improving bone mass and mineralization in experimental models. Preliminary experiments on murine models suggest that Ipamorelin may have mitigated the loss of muscle strength, which can occur in artificially-induced catabolic conditions.(8) The researchers also commented that introduction of the peptide appeared to have increased bone mineralization in the murine models subjected to a combination of Ipamorelin and catabolism-inducing agents, in contrast to the control group receiving only catabolism-inducing agents. Other trials on experimental murine models also suggest that Ipamorelin may elevate bone mineral content, pointing toward denser and more robust bone formation.(9) The researchers utilized dual X-ray absorptiometry (DEXA) to observe the potential impact of Ipamorelin on bone mineral density in real-time, focusing on areas like the femur and L6 vertebrae. Post-research, the femurs of the murine subjects were analyzed using mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. The DEXA observations hint at a possible increase in tibial and vertebral BMC (bone mineral content) due to the peptide, differing from the control group. Additionally, the pQCT findings imply that the enhanced cortical BMC might stem from an expanded cross-sectional bone area, suggesting that the femur and L6 vertebrae could have seen heightened bone mineralization. Fragment 176-191 & Modified GRF 1-29 & Ipamorelin Blend and Appetite Ipamorelin appears to activate the ghrelin receptors in the pituitary (GHSR1a) but may also trigger the receptors for ghrelin in other systems. Considering its potential impact on ghrelin receptors, Ipamorelin may enhance appetite, possibly leading to weight gain. Research indicates that Ipamorelin might have contributed to an approximate 15% increase in the body weight of murine models.(10) Some theories suggest that Ipamorelin may have proportionally increased fat pad weights relative to total body weight, resulting in a noticeable rise in body fat, as detected by DEXA. Additionally, there are hints that Ipamorelin may have boosted serum leptin levels, a hormone associated with energy and appetite control. As a result, researchers theorize that murine models in the Ipamorelin groups could have consumed more food, leading to the observed weight gain. Fragment 176-191 & Modified GRF 1-29 & Ipamorelin peptide blend is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 91976842, CJC1295 Without DAC. https://pubchem.ncbi.nlm.nih.gov/compound/CJC1295-Without-DAC. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001 Dec;142(12):5182-9. doi: 10.1210/endo.142.12.8522. PMID: 11713213. https://pubmed.ncbi.nlm.nih.gov/11713213/ National Center for Biotechnology Information (2023). PubChem Substance Record for SID 319360420, 386264-39-7, Source: ToxPlanet. https://pubchem.ncbi.nlm.nih.gov/substance/319360420 National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 9831659, Ipamorelin. https://pubchem.ncbi.nlm.nih.gov/compound/Ipamorelin. Sigalos, John T, and Alexander W Pastuszak. “The Safety and Efficacy of Growth Hormone Secretagogues.” Sexual medicine reviews vol. 6,1 (2018): 45-53. doi:10.1016/j.sxmr.2017.02.004 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632578/ News, Medical and Life Sciences, Obesity drug codenamed AOD 9604 highly successful in trials, 16 December 2004, https://www.news-medical.net/news/2004/12/16/6878.aspx. Kwon DR, Park GY. Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Ann Clin Lab Sci. 2015 Summer;45(4):426-32. PMID: 26275694. https://pubmed.ncbi.nlm.nih.gov/26275694/ Andersen, N. B., Malmlöf, K., Johansen, P. B., Andreassen, T. T., Ørtoft, G., & Oxlund, H. (2001). The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 11(5), 266–272. https://doi.org/10.1054/ghir.2001.0239 Svensson, J., Lall, S., Dickson, S. L., Bengtsson, B. A., Rømer, J., Ahnfelt-Rønne, I., Ohlsson, C., & Jansson, J. O. (2000). The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. The Journal of endocrinology, 165(3), 569–577. https://doi.org/10.1677/joe.0.1650569 Lall, S., Tung, L. Y., Ohlsson, C., Jansson, J. O., & Dickson, S. L. (2001). Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues. Biochemical and biophysical research communications, 280(1), 132–138. https://doi.org/10.1006/bbrc.2000.4065 Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Follistatin-344 (1mg)
Follistatin-344 is a naturally occurring glycoprotein that is considered to be present in almost all tissues. It is considered an autocrine chemical, meaning that the cell produces a chemical messenger through a cell signal, which binds to its autocrine receptors, resulting in cell modification.(1) Follistatin naturally occurs in two isoforms, FST 317 and FST 344, each containing 288 and 315 amino acids, respectively. These two isoforms may be produced through an alternative splicing process of the mRNA.(2) Their names are based on the parent molecules from which they are derived and contain 317 and 344 amino acids, respectively. Follistatin-344 is considered to be the predominantly expressed molecule in most tissues, while the Follistatin-317 isoform may account for less than 5% of the encoded mRNA. Follistatin-344 is a synthetic version of the endogenous Follistatin-344 protein isoform. Although the number of amino acids differs in Follistatin isoforms, at its core, the protein comprises 63 amino acid residues and three domains: FSD1, FSD2, and FSD3, with an identical structure in the synthetic peptide.(3) These domains comprise 73-77 amino acid residues and are characterized by 10 conserved cysteine residues. Overview Researchers posit that Follistatin's primary potential may exist in activin-binding action.(4) Follistatin has been suggested to have a collaborative role in reproductive functioning alongside other chemicals like activin and inhibins. Scientists posit that the ovarian follicle mainly releases activin to enhance the secretion of follicle-stimulating hormone. Follistatin may bind with activin and attenuate its action by inhibiting the secretion of the FSH hormone. While the origin and mechanism of the peptide hormone are not entirely understood, it has been suggested that Follistatin-344 is locally produced in the pituitary gland, gonads, testes, and ovaries. Additionally, Follistatin may be vastly distributed in various organs and potentially may be present in blood circulation due to its secretion from the blood vessels. Further, Follistatin-344 is hypothesized to interact with various proteins within the Transforming Growth Factor-beta (TGFβ) superfamily.(16) This superfamily includes several key regulatory proteins in cellular growth and differentiation. One potential interaction is with the Bone Morphogenetic Proteins (BMPs), which are believed to play roles in bone formation, embryonic development, and cellular growth. It is conjectured that Follistatin-344 might modulate the activity of certain BMPs, though the specific proteins and mechanisms remain uncertain and require further exploration. Another possible interaction involves Growth Differentiation Factor 9 (GDF9), crucial for ovarian follicle development in female organisms. The binding of Follistatin-344 to GDF9 may suggest a regulatory role in reproductive processes, but this interaction is not fully understood and is subject to ongoing research. However, the most notable of these interactions is with Growth Differentiation Factor 8 (GDF8), commonly known as myostatin. Myostatin is deemed integral to controlling muscle cell growth and differentiation, acting as a natural inhibitor to prevent excessive muscle development. It is proposed that Follistatin-344 binds to myostatin, potentially inhibiting its function. This inhibition may theoretically facilitate an increase in muscle mass by allowing muscle cells greater freedom to grow and differentiate. The potential for Follistatin-344 to enhance muscle growth through myostatin inhibition presents a significant area of interest, although the actual outcomes may vary and are highly dependent on singular biological conditions. Chemical Makeup Molecular Formula: N/A Molecular Weight: 3780 g/mol Other Known Titles: Activin-Binding Protein, FSH-Suppressing Protein, FST Research and Clinical Studies Follistatin-344 and Muscle Development Myostatin is a protein considered to be synthesized by muscle cells, hindering muscle cell differentiation and growth. As mentioned, myostatin protein belongs to the transforming growth factor-beta (TGF-beta) protein, which Follistatin may inhibit. During one 1997 study,(5) it was suggested that mice given Follistatin-344 exhibited reduced levels of myostatin, which might have led to the improved skeletal muscle mass with each mouse weighing 2 to 3 times more than usual, and the increase in mass appeared to result from a combination of muscle cell hyperplasia and hypertrophy. In another study,(6) Follistatin-344 was induced in mice via a nanoparticle-mediated mode of delivery of mRNA in the liver. The researchers reported that the mRNA messenger appeared to stimulate the hepatic liver cells to naturally synthesize and secrete Follistatin. Results of this study suggested that the peptide mice, given this mRNA-containing nanoparticle, exhibited apparently increased serum levels of Follistatin within three days as compared to the levels in control mice. The research posits that Follistatin mRNA is translated in the liver, leading to increased serum levels of Follistatin. This elevation in Follistatin was suggested to persist for up to 72 hours post-presentation and was associated with decreased serum concentrations of myostatin and activin A. Activin A is a protein considered to be involved in a myriad of biological processes. It is a member of the transforming growth factor-beta (TGF-β) superfamily. It appears to play significant roles in regulating various cellular functions such as proliferation, differentiation, and apoptosis in numerous cell types. In the context of muscle physiology, activin A is particularly noteworthy for its role in muscle metabolism and remodeling. It is thought to be a critical regulator of muscle mass, as it appears to negatively influence muscle growth by promoting catabolic pathways that lead to muscle atrophy. This action is mediated primarily through its interaction with the activin type IIB receptor (ActRIIB) on muscle cells. Upon binding to this receptor, activin A activates intracellular signaling pathways that increase muscle protein breakdown and inhibit muscle protein synthesis. After 8 weeks of continuous peptide presentation, the lean muscle mass of the peptide mice was reportedly 10% more than the control mice. In contrast to experiments targeting myostatin—such as anti-myostatin antibodies—Follistatin offers a broader research approach by also antagonizing activin A. Myostatin-specific experiments primarily focus on inhibiting pathways that directly limit muscle growth, thus promoting hypertrophy. However, they might not address other pathways that contribute to muscle loss, such as fibrosis or inflammation, which are influenced by activin A. Follistatin’s dual antagonistic action might lead to more comprehensive impact in muscle dystrophy models. By inhibiting both myostatin and activin A, Follistatin may not only enhance muscle mass but also reduce muscle stiffness and weakness associated with fibrotic changes. This potential dual action is particularly advantageous because it may address both the loss of muscle mass and the quality of the remaining muscle tissue, potentially leading to improvements in muscle function and strength that surpass those achieved by solely blocking myostatin.(7) Follistatin-344 and Carcinogenic Cells Breast Cancer Cells Through reverse transcription polymerase chain reaction study (RT-PCR), researchers suggested that Follistatin levels may fluctuate in animal models of breast cancer.(8) One study(9) examined the available gene expression data of mice with breast cancer. In most cases, Follistatin was reportedly under-expressed in carcinogenic breast cells, possibly leading to the increased spread of cancer cells caused by activin proteins. As Follistatin is suggested to bind to and inhibit activin proteins, it was further posited by the researchers that restoring Follistatin in these mice might prevent the prognosis of activin-induced metastasis and improve overall survival. Esophageal Cancer Cells Research suggests that bone morphogenic protein (BMP) is one of the causative factors in the transition of normal esophageal tissue to cancerous tissues. Follistatin, speculated to host the capacity to bind and neutralize activin and myostatin, may also interact with BMPs. By modulating the activity of BMP, Follistatin may serve a protective role against the over-proliferation of cellular pathways often seen in cancerous tissues. Experimental studies in Follistatin-344 suggest that the peptide may counteract acid reflux actions, thereby possibly preventing an over-activation of BMP and the development of esophageal cancer cells. More specifically, Follistatin's potential to inhibit BMP might theoretically prevent the initial steps required for the transformation of normal tissue into cancerous tissue, particularly in environments exacerbated by chronic inflammation or external insults like acid reflux.(10) Follistatin-344 and Cell Proliferation There is an odd contrast in the working of Follistatin: it may potentially inhibit metastasis, as well as possibly promote cell proliferation. This is why the peptide is researched in studies scrutinizing increased tumor growth (tumorigenesis) and metastasis.(12) Research has suggested that hepatocytes (i.e., liver cells) may require Follistatin to proliferate. When studied in experimental rats, it was reported by the researchers that the inactivation of activin by Follistatin-344 may be a precondition for cell proliferation to occur. They believed there might be some energy exchange amongst the cells where the energy used for cell migration is shut off to switch with cellular growth and proliferation. Follistatin-344 and Liver Protection One study(13) was conducted to determine the potential of Follistatin on early liver fibrosis. In this study, rats were divided into one control group and one Follistatin-exposed group for a period of four weeks. Researchers reported that the peptide group showed a 32% decrease in liver fibrosis compared to the control group. They further reported that hepatocytic apoptosis was decreased by almost 90% in the Follistatin mice. Follistatin-344 and Follicle Growth Follistatin may exhibit wound healing potential via possible stimulation of interfollicular stem cells, which may lead to increased hair growth. A clinical study was conducted where the potential of this synthetic protein formulation, Hair Stimulating Complex (HSC), was studied in subjects with hair loss.(14) A cohort of 26 subjects were presented with the peptide for a period of 52 weeks. Histopathological evaluation of the tissues reportedly showed improved hair growth after 52 weeks compared to the control group. Besides hair growth, researchers reported an apparent improvement in hair thickness and density by almost 13%. Follistatin-344 and Diabetic Mice Models Researchers suggested that when Follistatin-344 was presented to diabetic murine models, it appeared to lead to overexpression of the protein in the pancreatic cells, resulting in increased pancreatic beta cell (β-cell) mass, reduced glucose level, and overall reduction in diabetic symptoms.(15) β-cells are a population of cells in the pancreas primarily tasked with producing insulin to lower glucose levels. The data suggest that this β-cell proliferation is possibly due to the inhibition of SMAD2/3 signaling, a pathway typically activated by transforming growth factor-beta (TGF-β) superfamily members such as activin and myostatin, which are believed to be antagonized by Follistatin. This inhibition might indirectly activate the insulin-phosphoinositide 3-kinase (PI3K)-Akt pathway, posited as crucial for cell growth and survival, potentially contributing to increased β-cell mass and improved glucose homeostasis. The researcher’s comments suggest that β-cell specific overexpression of Follistatin may lead to several notable outcomes in the tested db/db mice: a substantial increase in pancreatic islet mass, enhanced β-cell proliferation indicated by co-immunofluorescent staining for Ki67 and insulin, and improved overall metabolic profiles including reduced hyperglycemia. It is also noted that these actions were accompanied by changes in insulin signaling within the pancreas, as detailed by elevated insulin levels and enhanced activation of the insulin-PI3K-Akt signaling pathway. Moreover, the study posits that Follistatin may influence the expression of other regulatory proteins and genes within the pancreas. For instance, the increased mRNA levels of myostatin and activin, along with their inhibitors BAMBI and inhibin-α, suggest a complex interplay where Follistatin may act to modulate these signaling molecules, possibly leading to an enhanced β-cell proliferative environment. Additionally, the study explores the potential modulation of betatrophin, a hormone implicated in β-cell proliferation. The researchers observed a significant increase in betatrophin expression in the Follistatin groups, which might be facilitated by the suppressed activity of activin and myostatin due to Follistatin action. This suggests that Follistatin may be enhancing β-cell proliferation not only through direct inhibition of negative growth regulators but also by promoting positive growth signals such as betatrophin. Follistatin-344 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Hiroyuki Kaneko, Handbook of Hormones, 2016. FST follistatin [Homo sapiens (human)]. https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=DetailsSearch&Term=10468 Shi, L., Resaul, J., Owen, S., Ye, L., & Jiang, W. G. (2016). Clinical and Therapeutic Implications of Follistatin in Solid Tumours. Cancer genomics & proteomics, 13(6), 425–435. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219916/ Rodino-Klapac, L. R., Haidet, A. M., Kota, J., Handy, C., Kaspar, B. K., & Mendell, J. R. (2009). Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle & nerve, 39(3), 283–296. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717722/ McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997 May 1;387(6628):83-90. https://pubmed.ncbi.nlm.nih.gov/9139826/ Schumann C, Nguyen DX, Norgard M, Bortnyak Y, Korzun T, Chan S, Lorenz AS, Moses AS, Albarqi HA, Wong L, Michaelis K, Zhu X, Alani AWG, Taratula OR, Krasnow S, Marks DL, Taratula O. Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA. Theranostics 2018; 8(19):5276-5288. doi:10.7150/thno.27847. https://www.thno.org/v08p5276.htm Iskenderian A, Liu N, Deng Q, Huang Y, Shen C, Palmieri K, Crooker R, Lundberg D, Kastrapeli N, Pescatore B, Romashko A, Dumas J, Comeau R, Norton A, Pan J, Rong H, Derakhchan K, Ehmann DE. Myostatin and activin blockade by engineered follistatin results in hypertrophy and improves dystrophic pathology in mdx mouse more than myostatin blockade alone. Skelet Muscle. 2018 Oct 27;8(1):34. https://pubmed.ncbi.nlm.nih.gov/30368252/ Zabkiewicz C, Resaul J, Hargest R, Jiang WG, Ye L. Increased Expression of Follistatin in Breast Cancer Reduces Invasiveness and Clinically Correlates with Better Survival. Cancer Genomics Proteomics. 2017 Jul-Aug;14(4):241-251. https://pubmed.ncbi.nlm.nih.gov/28647698/ Seachrist DD, Sizemore ST, Johnson E, Abdul-Karim FW, Weber Bonk KL, Keri RA. Follistatin is a metastasis suppressor in a mouse model of HER2-positive breast cancer. Breast Cancer Res. 2017 Jun 5;19(1):66. target="_blank" rel="noopener"https://pubmed.ncbi.nlm.nih.gov/28583174/ Lau MC, Ng KY, Wong TL, Tong M, Lee TK, Ming XY, Law S, Lee NP, Cheung AL, Qin YR, Chan KW, Ning W, Guan XY, Ma S. FSTL1 Promotes Metastasis and Chemoresistance in Esophageal Squamous Cell Carcinoma through NFκB-BMP Signaling Cross-talk. Cancer Res. 2017 Nov 1. https://pubmed.ncbi.nlm.nih.gov/28883005/ Shi L, Resaul J, Owen S, Ye L, Jiang WG. Clinical and Therapeutic Implications of Follistatin in Solid Tumours. Cancer Genomics Proteomics. 2016 11-12;13(6):425-435. https://pubmed.ncbi.nlm.nih.gov/27807065/ Ooe H, Chen Q, Kon J, Sasaki K, Miyoshi H, Ichinohe N, Tanimizu N, Mitaka T. Proliferation of rat small hepatocytes requires follistatin expression. J Cell Physiol. 2012 Jun;227(6):2363-70. https://pubmed.ncbi.nlm.nih.gov/21826650/ Patella S, Phillips DJ, Tchongue J, de Kretser DM, Sievert W. Follistatin attenuates early liver fibrosis: effects on hepatic stellate cell activation and hepatocyte apoptosis. Am J Physiol Gastrointest Liver Physiol. 2006 Jan;290(1):G137-44. https://pubmed.ncbi.nlm.nih.gov/16123203/ Zimber MP, Ziering C, Zeigler F, Hubka M, Mansbridge JN, Baumgartner M, Hubka K, Kellar R, Perez-Meza D, Sadick N, Naughton GK. Hair regrowth following a Wnt- and follistatin containing treatment: safety and efficacy in a first-in-man phase 1 clinical trial. J Drugs Dermatol. 2011 Nov;10(11):1308-12. https://pubmed.ncbi.nlm.nih.gov/22052313/ Zhao C, Qiao C, Tang RH, Jiang J, Li J, Martin CB, Bulaklak K, Li J, Wang DW, Xiao X. Overcoming Insulin Insufficiency by Forced Follistatin Expression in β-cells of db/db Mice. Mol Ther. 2015 May;23(5):866-874. doi: 10.1038/mt.2015.29. Epub 2015 Feb 13. PMID: 25676679; PMCID: PMC4427879. https://pubmed.ncbi.nlm.nih.gov/25676679/ Reichel C, Gmeiner G, Thevis M. Detection of black market follistatin 344. Drug Test Anal. 2019 Nov;11(11-12):1675-1697. doi: 10.1002/dta.2741. Erratum in: Drug Test Anal. 2020 Oct;12(10):1522-1533. PMID: 31758732. Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
B7-33 (6mg)
H2-relaxin is a naturally occurring, endogenous protein compound, which was synthetically mimicked and named the “B7-33” peptide. The H2-relaxin protein class comprises relaxin, H3-relaxin, insulin-like peptide-3, and insulin-like peptide-5. All these proteins have been suggested to exhibit a variety of biological actions, including possibly affecting genetic functions and the reproductive, musculoskeletal, and cardiovascular systems.(2) Considered structurally similar to H2-relaxin, the synthetic equivalent B7-33 may possess anti-fibrotic potential. There are four different receptors that these naturally produced relaxin proteins are speculated to bind with, namely RXFP-1, RXFP-2, RXFP-3, and RXFP-4. Each receptor has a different action, as outlined below:(2) RXFP-1 receptor is suggested to influence sperm motility RXFP-2 receptor appears to impact testicular development RXFP-3 receptor may play a role in circadian rhythm and sleep cycle regulation RXFP-4 receptor has shown indications of affecting hunger hormone signaling cycles Due to the variety of receptors involved and a wide range of biological impact, extensive research has been conducted on the relaxin protein and its analogs, such as the B7-33 peptide, to fully understand their potential. Overview B7-33 is a singular chain peptide, a smaller analogous derivative of the endogenous relaxin protein.(3) Typically, the relaxin peptide comprises four components - a signal peptide, B chain, C chain, and COOH terminal. Several studies were conducted initially to replicate these peptide structures, however the researchers reported that results indicated it being highly insoluble and inactive. After extensive subsequent research, scientists modified the structure by producing a B chain and elongating the COOH terminal, thereby forming the first-ever soluble analog - B7-33 peptide - in 2016.(3) Besides the structural difference, the peptide has other variations from the endogenous protein. B7-33 peptide has been suggested to act via the pERK pathway instead of the cAMP pathway. The pERK pathway is a signaling route within cells that may affect cell function, often related to cell growth and survival. In contrast, the cAMP pathway involves different cellular activities primarily related to energy balance and metabolism. H2-relaxin has been suggested to produce antifibrotic potential via the cAMP pathway, which may stimulate tumor formation.(1) Furthermore, the peptide may have a strong affinity towards the RXFP-1 receptors. The peptide appears to bind with these RXFP-1 receptors, stimulating the pERK pathway, which then may lead to increased synthesis of MMP-2 matrix metalloproteinase chemicals. MMP-2 is an enzyme that breaks down proteins and plays a crucial role in tissue remodeling and repair. These chemicals then possibly inhibit the scarring of tissues, thereby preventing fibrosis.(1) Fibrosis is considered the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process, which is associated with a loss of function. Chemical Makeup Molecular Formula: C131H228N40O37S Molecular Weight:2987,75 g/mol Other Known Titles: (B7-33)H2, GTPL9321 Research and Clinical Studies B7-33 Peptide and Vasoprotection This 2017 study(4) was conducted on male Wistar murine models where their tails were presented with a control compound (which was sodium acetate), H2 relaxin, or B7-33 peptide. After three hours, these mice were examined for their vascular functions, mainly in the mesenteric artery, renal artery, and abdominal aorta. While the results were not as promising in the renal artery and abdominal aorta, B7-33 and H2 relaxin exhibited potential vasodilatory properties in the mesenteric artery. Thus, the results suggest that both B7-33 and serelaxin may preferentially augment bradykinin-induced endothelium-dependent relaxation, particularly emphasizing the mesenteric artery in rats. This augmentation appears to be linked to enhanced endothelium-derived hyperpolarization. To understand better, the researchers reported an additional study(4) carried out in female murine models experimentally induced with endothelial dysfunction. These mice were then either given B7-33 or H2 relaxin. Following the study, the researchers suggested that both compounds may have helped combat and prevent the further spread of endothelial dysfunction in mice. These results suggest that B7-33 has the potential to replicate the vasoprotective action of H2 relaxin and thereby protect blood vessels from further damage. B7-33 Peptide and Preeclampsia Preeclampsia is a pregnancy ailment characterized by increased hypertension in mothers and decreased fetal weight. This clinical study(5) was conducted to understand the potential of B7-33 peptide in pregnant females with preeclampsia. A cell culture of cytotrophoblasts (CTBs) was used. Cytotrophoblasts are the cells found in the inner cellular layer of the embryo. These cells were given either control compound, a marinobufagenin steroid, or glucose for two days. Following this preparation, some of these cells were given either a relaxin antagonist, or the B7-33 compound. Upon examination, the cells given B7-33 peptide appeared to exhibit an upregulation of the vascular endothelial growth factor, VEGF. Cells that were given relaxin antagonists exhibited apparent reduced VEGF concentration. VEGF is thought to stimulate the proliferation and migration of endothelial cells, which line the interior surfaces of blood vessels. By potentially enhancing these processes, VEGF may play a vital role in forming new vascular structures, essential for supplying tissues with oxygen and nutrients, especially during rapid growth or healing periods. VEGF's actions are primarily mediated through two tyrosine kinase receptors, VEGFR-1 and VEGFR-2, located on the surface of endothelial cells. The binding of VEGF to these receptors is thought to trigger a cascade of signaling pathways that could lead to endothelial cell proliferation, migration, and survival. B7-33 Peptide and Anti-Fibrosis Studies(6)(7) have suggested that when presented with a fully extended strain of H2 relaxin protein, it may induce an increased heart rate and possibly stimulate the spread of carcinogenic cells. This is mainly attributed to its mechanism as it appears to activate the cAMP pathway. Hence, researchers are looking for a derivative that might produce the exact biological action of anti-fibrosis without cAMP activation. When the peptide was exposed in mice with myocardial infarction, it was reported to result in almost 50% reduction in cardiac tissue fibrosis. Furthermore, a study(1) was also conducted in mice with prostate diseases. These mice were presented with two different concentrations of B7-33 peptide. At both concentrations, the results were the same, and researchers suggested that the compound might contribute to the development of fibrosis without promoting the spread of prostate tumors. This suggested that the peptide may have the potential to act via the pERK pathway and not via cAMP activation. The designation "pERK" refers to the phosphorylated state of extracellular signal-regulated kinase (ERK), indicating its activated status. It is hypothesized that the activation pathway initiates when a growth factor interacts with its corresponding receptor on the cellular surface, potentially activating the receptor's intrinsic kinase capabilities. This interaction is believed to initiate a sequence of phosphorylation events, transmitting the signal through a network of intermediary proteins, such as RAF and MEK (MAPK/ERK kinase). This sequence is thought to ultimately result in the phosphorylation and subsequent activation of ERK. Following activation, it is suggested that ERK translocates to the nucleus where it may phosphorylate various transcription factors, potentially leading to changes in gene expression that might influence cellular processes, including division and differentiation. B7-33 Peptide as a Coating Material In one animal study(8), a peptide-coated device was implanted in murine models. The researchers were curious to see if the peptide might counteract possible fibrotic actions in the mice. As a result of this peptide release from the device coating, the reduction in device thickness (by fibrosis) was reported to be decreased by 49.2% over the 6-week duration of the study. B7-33 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Mohammed Akhter Hossain et al, A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1, Drug Discovery Biology Pharmacology Monash Biomedicine Discovery Institute, Vol 7, 2016. R J Summers, Recent progress in the understanding of relaxin family peptides and their receptors, British Journal of Pharmacology, Vol 174, issue 10, pg 915-920. https://doi.org/10.1111/bph.13778 Nitin A Patil et al, Relaxin family peptides: structure–activity relationship studies, British Pharmacological Society, vol 174 issue 10, published 06 December 2016. https://doi.org/10.1111/bph.13684 Marshall SA, O'Sullivan K, Ng HH, Bathgate RAD, Parry LJ, Hossain MA, Leo CH. B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin). Eur J Pharmacol. 2017 Jul 15;807:190-197. doi: 10.1016/j.ejphar.2017.05.005. Epub 2017 May 3. PMID: 28478069. https://pubmed.ncbi.nlm.nih.gov/28478069/ S.H Afroze et al, Abstract P3042: Novel Peptide B7-33 and It's Lipidated Derivative Protect Cytotrophoblasts From Preeclampsia Phenotype in a Cellular Model of the Syndrome, 4 Sep 2019. https://doi.org/10.1161/hyp.74.suppl_1.P3042 Silvertown JD, Ng J, Sato T, Summerlee AJ, Medin JA. H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis. Int J Cancer. 2006 Jan 1;118(1):62-73. https://pubmed.ncbi.nlm.nih.gov/16049981 Shu Feng, Irina U. Agoulnik, Natalia V. Bogatcheva, Aparna A. Kamat, Bernard Kwabi-Addo, Rile Li, Gustavo Ayala, Michael M. Ittmann and Alexander I. Agoulnik, Relaxin Promotes Prostate Cancer Progression, March 2007. https://clincancerres.aacrjournals.org/content/13/6/1695 N.Welch et al, Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic Encapsulation, ACS Applied Materials and Interfaces, Nov 2019. www.researchgate.net/publication/337205944_Coatings_Releasing_the_Relaxin_Peptide_Analogue_B7-33_Reduce_Fibrotic_Encapsulation Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Humanin (10mg)
Humanin is a short natural peptide with suggested potential in cell metabolism and inflammation response.(3) Researchers have suggested that a mitochondrial genome called ‘16S ribosomal RNA gene’ encodes the Humanin peptide.(4) Researchers further posit that the peptide's length may depend on the location of its synthesis. The peptide may contain 21 amino acids if synthesized inside the mitochondria, whereas it may contain 24 amino acids if synthesized outside the mitochondria but inside the cytosol.(5) Both of these peptides exhibit potential biological activity. Mitochondria are considered the powerhouses of the cell, and are formed from the engulfment of individual prokaryotes. Eventually, the eukaryotes appear to engulf the prokaryotic (single-celled) organism, and the prokaryotes form an endosymbiotic relationship with the host cell and gradually develop into mitochondria.(1) Mitochondria are considered to be responsible for several vital cellular activities, including energy production, regulation of apoptosis, hemostasis, and formation of heme proteins, among several other functions. All these functions appear to be regulated by mitochondria via their communications to the cell through several retrograde signals. These signals may be encoded by the nuclear genome present in the mitochondria, possibly due to its prokaryotic origin.(2) A small peptide called Humanin is derived from this genome. Since this genome appears to play an important role, this peptide has been explored for its potential action in several biological functions. Overview The peptide appears to exert potential actions via binding with intracellular molecules and cell membrane receptors, possibly inducing cytoprotective and/or neuroprotective functions.(9) Researchers suggest that Humanin may bind with the Bcl-2-associated X protein (also called Bax protein). Bax protein is considered to play a vital role in cellular death (apoptosis). Upon binding with the inactive form of the Bax protein, Humanin may inhibit the changes in the Bax protein and potentially thereby prevent cellular apoptosis.(9) Apart from research into its possible interaction with Bax, Humanin studies suggest the peptide may also bind with other intracellular molecules, such as actinin-4 and phosphoprotein 8, which are both involved in cellular apoptosis. Upon binding with these proteins, Humanin may induce cytoprotective actions. Researchers suggest Humanin may bind with two G protein-coupled peptide receptors, namely FPRL-1 and FPRL-2 receptors, which are considered to be involved with neurological function.(9) By binding with this receptor, Humanin may potentially prevent amyloid β binding with the FPRL-1 and FPRL-2 receptors, which may mitigate some instances of neurological degradation. Chemical Makeup Molecular Formula: C119H204N34O32S2 Molecular Weight: 2687.3 g/mol Other Known Titles: HNGF6A protein Research and Clinical Studies Humanin Peptide and Mitochondrial Functions Mitochondria appear to be susceptible to reactive oxygen species (ROS), and the presence of such ROS may reduce its functioning. Studies in Humanin mechanisms of action suggest that the peptide may inhibit these reactive oxygen species to some degree, thereby mitigating mitochondria degeneration.(10) One study was produced wherein the researchers attempted to explore the peptide's action on retinal pigment epithelial cells. These cells were isolated and introduced to tert-butyl hydroperoxide to exert oxidative stress in the cells. Some of these cells were then presented with Humanin peptide for 24 hours. When examined, the cells exposed to Humanin reportedly inhibited the formation of tert-butyl hydroperoxide-induced reactive oxygen species. The researchers suggested the peptide may have restored the bioenergetics in the retinal pigment epithelial cells and increased the functioning of mitochondria. Humanin Peptide and Cellular Longevity Studies(11) were conducted on several murine models to determine the relation between Humanin with growth hormone (GH) and immunoglobulin (IGF-1). In GH-transgenic murine models, the levels of growth hormone and IGF-1 appeared to be extremely high, which the researchers suggested led to increased body size, accelerated cell aging, and reduced life span. Researchers reported that the levels of Humanin naturally present in the murine models were extremely low, about 70% lower than the control. Another set of murine models had undetectable levels of GH and IGF-1, along with a reported 40% increase in the Humanin levels. These murine models showed an increased life span compared to normal murine models. These results supported the researchers' hypothesis that Humanin may be negatively correlated to GH and IGF-1 levels and directly correlated to cellular longevity. Humanin Peptide and Neurological Deterioration A study(12) was conducted on 9-month-old murine models, all of which reportedly possessed high levels of amyloid proteins. These amyloid chemicals are indicative of some neurological deterioration. Some murine models were presented with Humanin, while others were given a placebo. Following the study, the researchers suggested that the placebo models showed impaired memory and poor learning skills. In contrast, the murine models presented with Humanin for 3 months reportedly exhibited significantly improved learning ability and enhanced memory. In another study,(13) murine models with experimentally induced impairment in neurological functioning were exposed to Humanin and a similarly structured peptide, PAGA, to determine the potential of both peptides on the brain function of the murine models. Both the peptides showed some modest improvement in the impairment of the brain, as suggested by the researchers. Another study explored the potential neuroprotective action of Humanin on neurotoxicities induced by Calyculin A in cortical neurons as a model of exposure to neurotoxins. The researchers focused on the potential capability of the peptide to safeguard cortical neurons from Calyculin A-induced neurotoxic action. In this investigation, cortical neurons were preincubated with Humanin to examine its protective role against neurotoxicity. The methodologies utilized in this research included employing 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and Calcein-AM assays to evaluate the extent of neural damage. Furthermore, caspase 3 signaling and TUNEL assays were conducted to assess neural apoptosis. The study also used Western blot analysis to detect potential expressions of phosphorylated tau, a protein associated with neurodegenerative diseases. Additionally, the study measured the apparent contents of malondialdehyde (MDA) and superoxide dismutase (SOD), and the activity of protein phosphatase 2A (PP2A), which are potential indicators of oxidative stress in neurons. The results from these investigations posited that preincubation with Humanin may preserve cell viability and potentially protect neurons from Calyculin A-induced damage. Notably, the peptide appeared to alleviate oxidative stress in the neurons and preserved the activity of PP2A, an enzyme involved in dephosphorylating tau proteins. Humanin also may have inhibited the over-phosphorylation of tau at specific sites (Ser199/202, Ser396, and Thr231), which are considered critical to the pathological changes observed in neurodegenerative diseases. From these findings, it was inferred that Humanin potentially offered protective action against neurotoxicities induced by harmful agents like Calyculin A.(14) Humanin Peptide and Insulin Resistance To determine the potential of Humanin on insulin resistance, a study(15) was conducted on nonobese diabetic murine models. When a group of these models were presented with Humanin, it appeared to restore to some degree the levels of glucose tolerance within 6 weeks. Furthermore, Humanin also potentially delayed the onset of diabetes in the murine models presented with the peptide for 20 weeks. Researchers suggested that following the study results, Humanin may exhibit some action in insulin resistance. In another study,(16) 12-week-old murine models were subjected to a 60% high-fat diet and were presented with Humanin for 4 weeks. After the study, there appeared to be no difference in the food intake. However, the weight gain had reportedly been reduced by about 20%. Furthermore, there appeared to be a high expenditure of energy, decreased fasting glucose levels, and increased insulin levels. Another study also explored the potential role of Humanin in influencing insulin sensitivity. The investigation suggested that continuous exposure of Humanin to the central nervous system of murine models appeared to enhance overall insulin sensitivity. This improvement in insulin action seemed to be linked to the activation of STAT-3 (Signal Transducer and Activator of Transcription 3) signaling within the hypothalamus. However, this action was negated when hypothalamic STAT-3 was co-inhibited, suggesting a potential role of this signaling pathway in mediating Humanin actions on insulin sensitivity. Furthermore, centrally-acting Humanin also appeared to improve insulin resistance in peripheral tissues such as liver cells. Ultimately, this appeared to result in reduced blood glucose levels in the murine models.(17) Humanin Peptide and Hypoxia A study(18) was conducted in which the isolated retinal cells were exposed to cobalt chloride, which appeared to induce hypoxia, leading to cell apoptosis. When the hypoxia-induced cells were presented with Humanin, researchers reported that the peptide appeared to reverse the impact of cobalt chloride and protect the cell from reduced oxygen levels. Additional studies (19) have suggested that Humanin may possibly increase metabolic activity and, thereby, cell survival rates in the event of lymphocyte death, which has some implications in ischemia. Humanin Peptide and Ischemia This study(20) was conducted to further examine the neuroprotective potential of Humanin in the presence of cerebral ischemia. In this study, murine models were experimentally induced with cerebral artery occlusion. Murine models were presented with low concentrations of Humanin for 30 minutes and then, following the procedure, were reintroduced to Humanin at 0, 2, 4, and 6 hours after ischemia. Other murine models were solely presented with Humanin one hour before ischemia. It was suggested that continual introduction to the peptide appeared to reduce the ischemia volume by almost 30%. Humanin presence following ischemia reportedly further reduced the ischemic impact. Another study on Humanin investigating its potential in mitigating ischemia in cells suggests that the peptide may be capable of reducing infarct size in murine models.(21) In this notable study, researchers suggested that Humanin may exhibit a potential to significantly reduce infarct size by 41% in a large animal model when introduced alongside standard reperfusion intervention after an ischemic period of 60 minutes, followed by 48 hours of reperfusion. However, it is important to note that the beneficial action of Humanin was not observed when the ischemic period was extended to 75 minutes, followed by the same duration of reperfusion, highlighting a potentially critical window for Humanin. The study also highlights that Humanin has been implicated in various protective roles across multiple organs, attributed to the potential to modulate oxidative stress, regulate insulin sensitivity, and inhibit apoptotic signaling, among other actions. Humanin Peptide Additional Studies Studies(22) have suggested that Humanin may bind with the FPR2 receptor in the brain, producing possible anxiolytic action. Consequently, the researchers of this study suggested that Humanin may potentially reduce anxiety symptoms. In this study,(23) murine carcinogenesis models were exposed twice weekly with an antineoplastic agent (used in cancer cases) and Humanin to explore their potential impact on the carcinogenic cells. While the control agent appeared to induce cell apoptosis, the combination of Humanin and the agent exhibited some potential, somewhat reversing the apoptosis of the healthy cells. Humanin peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: The origin of mitochondria and chloroplasts. https://www.nature.com/scitable/content/the-origin-of-mitochondria-and-chloroplasts-14747702/ Lee, Changhan et al. “Humanin: a harbinger of mitochondrial-derived peptides?.” Trends in endocrinology and metabolism: TEM vol. 24,5 (2013). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641182/ Gong, Zhenwei et al. “Humanin and age-related diseases: a new link?.” Frontiers in endocrinology vol. 5 210. 4 Dec. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255622/ Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6336-41. https://pubmed.ncbi.nlm.nih.gov/11371646/ Yen K, Lee C, Mehta H, Cohen P. The emerging role of the mitochondrial-derived peptide humanin in stress resistance. J Mol Endocrinol. 2013 Jan 11;50(1):R11-9. https://pubmed.ncbi.nlm.nih.gov/23239898/ Gong, Zhenwei et al. “Humanin and age-related diseases: a new link?.” Frontiers in endocrinology vol. 5 210. 4 Dec. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255622/ Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, Satterthwait AC, Reed JC. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature. 2003 May 22;423(6938):456-61. https://pubmed.ncbi.nlm.nih.gov/12732850/ Ikonen M, Liu B, Hashimoto Y, Ma L, Lee KW, Niikura T, Nishimoto I, Cohen P. Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13042-7. https://pubmed.ncbi.nlm.nih.gov/14561895/ Gong, Zhenwei et al. “Humanin and age-related diseases: a new link?.” Frontiers in endocrinology vol. 5 210. 4 Dec. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255622/ Sreekumar PG, Ishikawa K, Spee C, Mehta HH, Wan J, Yen K, Cohen P, Kannan R, Hinton DR. The Mitochondrial-Derived Peptide Humanin Protects RPE Cells From Oxidative Stress, Senescence, and Mitochondrial Dysfunction. Invest Ophthalmol Vis Sci. 2016 Mar;57(3):1238-53. https://pubmed.ncbi.nlm.nih.gov/26990160/ Changhan Lee et al, IGF-I regulates the age-dependent signaling peptide humanin. Published 18 July 2014, Vol 13 Issue 5. https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12243 Zhang W, Zhang W, Li Z, Hao J, Zhang Z, Liu L, Mao N, Miao J, Zhang L. S14G-humanin improves cognitive deficits and reduces amyloid pathology in the middle-aged APPswe/PS1dE9 mice. Pharmacol Biochem Behav. 2012 Jan;100(3):361-9. https://pubmed.ncbi.nlm.nih.gov/21993310/ Krejcova G, Patocka J, Slaninova J. Effect of humanin analogues on experimentally induced impairment of spatial memory in rats. J Pept Sci. 2004 Oct;10(10):636-9. https://pubmed.ncbi.nlm.nih.gov/15526713/ Zhao, J., Zeng, Y., Wang, Y., Shi, J., Zhao, W., Wu, B., & Du, H. (2021). Humanin protects cortical neurons from calyculin A-induced neurotoxicities by increasing PP2A activity and SOD. The International journal of neuroscience, 131(6), 527–535. https://doi.org/10.1080/00207454.2020.1769617 Hoang PT, Park P, Cobb LJ, Paharkova-Vatchkova V, Hakimi M, Cohen P, Lee KW. The neurosurvival factor Humanin inhibits beta-cell apoptosis via signal transducer and activator of transcription 3 activation and delays and ameliorates diabetes in nonobese diabetic mice. Metabolism. 2010 Mar;59(3):343-9. https://pubmed.ncbi.nlm.nih.gov/19800083/ Zhenwei Gong et al, Central effects of humanin on hepatic triglyceride secretion, Endocrinology and Metabolism. Muzumdar, R. H., Huffman, D. M., Atzmon, G., Buettner, C., Cobb, L. J., Fishman, S., Budagov, T., Cui, L., Einstein, F. H., Poduval, A., Hwang, D., Barzilai, N., & Cohen, P. (2009). Humanin: a novel central regulator of peripheral insulin action. PloS one, 4(7), e6334. https://doi.org/10.1371/journal.pone.0006334 Men J, Zhang X, Yang Y, Gao D. An AD-related neuroprotector rescues transformed rat retinal ganglion cells from CoCl₂-induced apoptosis. J Mol Neurosci. 2012 May;47(1):144-9. doi: 10.1007/s12031-011-9701-5. Epub 2012 Jan 5. https://pubmed.ncbi.nlm.nih.gov/22222604/ Kariya S, Takahashi N, Hirano M, Ueno S. Humanin improves impaired metabolic activity and prolongs survival of serum-deprived human lymphocytes. Mol Cell Biochem. 2003 Dec;254(1-2):83-9. https://pubmed.ncbi.nlm.nih.gov/14674685/ Xu X, Chua CC, Gao J, Hamdy RC, Chua BH. Humanin is a novel neuroprotective agent against stroke. Stroke. 2006 Oct;37(10):2613-9. Epub 2006 Sep 7. https://pubmed.ncbi.nlm.nih.gov/16960089/ Sharp, T. E., 3rd, Gong, Z., Scarborough, A., Goetzman, E. S., Ali, M. J., Spaletra, P., Lefer, D. J., Muzumdar, R. H., & Goodchild, T. T. (2020). Efficacy of a Novel Mitochondrial-Derived Peptide in a Porcine Model of Myocardial Ischemia/Reperfusion Injury. JACC. Basic to translational science, 5(7), 699–714. Zhao H, Sonada S, Yoshikawa A, Ohinata K, Yoshikawa M. Rubimetide, humanin, and MMK1 exert anxiolytic-like activities via the formyl peptide receptor 2 in mice followed by the successive activation of DP1, A2A, and GABAA receptors. Peptides. 2016 Sep;83:16-20. https://pubmed.ncbi.nlm.nih.gov/27475912/ Emma Eriksson, Malin Wickström, Lova Segerström Perup, John I. Johnsen, Staffan Eksborg, Per Kogner, Lars Sävendahl, Protective Role of Humanin on Bortezomib-Induced Bone Growth Impairment in Anticancer Treatment, JNCI: Journal of the National Cancer Institute, Volume 106, Issue 3, March 2014, djt459, https://doi.org/10.1093/jnci/djt459 Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
MGF (5mg)
MGF stands for Mechano Growth Factor, an endogenous, naturally occurring peptide that belongs to the class of IGF-1 (insulin-like growth factor) family.(1) What differentiates MGF from systemic IGF-1 is that it contains 49 base pairs at exon 5 in its structural composition, which may possibly introduce a frameshift to exert unique characteristics.(2) Researchers consider MGF to be an isoform of IGF-1, also known as IGF-1Ec (otherwise referred to as full-length MGF).(3) As IGF-1 undergoes alternative splicing and transcription, it appears to produce three isoforms. IGF-1 undergoes splicing under stress conditions, such as during resistance activities within muscle groups.(4) As a result of this splicing and due to the unique 49 base pair insert added to the peptide, it may produce a mature isoform of IGF-1, namely, naturally occurring MGF.(4) Overview During IGF-1 research studies, scientists first posited the phenomenon of IGF-1 splicing and isoform production. The only factor identified by the researchers that distinguished the three isoforms appears to be the amino acid sequence attached to the COOH terminal. It was only in the late 1990s and early 2000s that the uniqueness of IGF-1Ec was suggested when it was theorized that its levels increased upon muscle injury.(5) There is a synthetic version of the MGF peptide composed of 24 amino acids attached to the C-terminal of the isolated MGF domain, called MGF-Ct24E peptide, or E-domain of IGF-1Ec.(6) During the studies conducted in the early 2000s,(6) it was suggested that the MGF-Ct24E peptide may exhibit potential to induce muscle precursor cell proliferation. Muscle precursor cells are ‘satellite’ cells in myofiber, which increase to form new muscles. MGF is posited to increase in a growth hormone-dependent fashion, akin to IGF-1, which is also considered to potentially represent the main anabolic mediator of growth hormone. Studies suggest that growth hormones may also impact MGF expression by approximately 80%, relative to the baseline. In stark contrast, resistance activity in muscle tissue alone appears to elicit a response in MGF mRNA, with an increase of 163% from baseline. This immediate response may suggest a more direct or sensitive reaction of MGF to mechanical stimuli, yet the extent and nature of this sensitivity remain speculative. An apparent elevation of growth hormone that occurs in addition to resistance training might further complicate this response, as supported by a reported 456% increase in MGF mRNA.(7) Research studies are still underway to determine the mechanism of action of both the naturally occurring and synthetically developed MGF peptide. Hypotheses under investigation include the peptide's potential impact on damaged muscle cells, tissue repair and recovery, possible neuroprotective and cardioprotective characteristics, and potential impact on muscle cell apoptosis. Chemical Makeup Molecular Formula: C124H204N42O41S1 Molecular Weight: 2971.99 g/mol Other Known Titles: MGF-E, MGF-Ct24E Research and Clinical Studies MGF Peptide and Muscle Mass The main aim of one critical study on MGF(8) was to determine the potential of the synthetic peptide, aka the MGF-E domain made of 24 amino acids, on different aged cells. This was a study where muscle cell cultures, which ranged from neonatal to aged, were evaluated. The culture cells were analyzed after exposure to MGF-E. The peptide seemed to delay the onset of cellular senescence in younger cells, suggesting a potential to preserve muscle function and repair capabilities that diminish naturally. Furthermore, the results suggested cell proliferation in all cells isolated from neonatal to young cells; however, this was not the case in aged cells. Muscle hypertrophy appeared to be increased in the older cells, with a significant decrease in the reserve cells. It appeared to have induced hypertrophy in muscle cells across all ages by increasing the fusion index and the size of myotubes, which are formed from the fusion of muscle cells. The researchers observed that MGF-E may potentially also increase the expression of muscle-specific contractile proteins, indicating not only an increase in muscle cell size but also in functional capacity. Furthermore, the reduction in reserve cells appears notable as this may be a subpopulation of cells that do not initially differentiate or fuse into myotubes. MGF-E apparently led to a decreased proportion of these reserve cells in culture, suggesting that the peptide might prompt these cells to contribute to muscle formation. This finding is particularly noteworthy as it points to a mechanism by which MGF might potentially enhance muscle regeneration and maintenance. MGF Peptide and Muscle Recovery The main aim of another study(9) was to evaluate the potential of MGF on skeletal muscle injury repair and healing. This study was performed on mice that were experimentally induced with muscle contusion. Following Mechano Growth Factor (MGF) exposure and analysis of the muscle tissues, researchers suggested that MGF may have reduced the expressions of inflammatory markers such as cytokines and chemokines. Further, there was an apparent reduction of oxidative stress markers and matrix metalloproteinases (MMPs), suggesting that MGF might mitigate some inflammatory and fibrotic responses in muscle injury. As a result, the rate of contused muscles appeared to decline, which might induce long-term muscular repair of the wounded tissues. Moreover, the study hints that MGF may potentially not markedly impact the functional state of satellite cells following injury and immune cell depletion at the injury site, which is integral to muscle regeneration. This inference is drawn from observing unaltered expression levels of MyoD and myogenin—key satellite cell proliferation and differentiation indicators, respectively. This suggests that while MGF might potentially ease certain aspects of the muscle injury response, its direct action on satellite cell activity under the explored conditions remains uncertain. Subsequent examinations suggest that MGF exposure might influence fibrosis in injured muscle by possibly reducing the expression of collagen types I and III, crucial for the extracellular matrix and fibrotic development. The study further hints that MGF may play a part in adjusting the inflammatory setting within injured muscles. This is somewhat illustrated by a purported reduction in the expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, TGF-β) and chemokines (CCL2, CCL5, CXCR4) post-MGF exposure. Moreover, there's a speculative suggestion that MGF might assist in alleviating oxidative stress in injured muscle, indicated by a possible decrease in the expression of gp91phox, a vital component of NADPH oxidase implicated in the production of reactive oxygen species. MGF Peptide and Anti-Apoptotic Potential The main goal of this study(10) was to evaluate the potential of MGF on cardiac muscles undergoing programmed cell death (apoptosis) following hypoxia, a condition characterized by limited supply of oxygen. The study reported that the peptide appeared to induce increased migration of stem cells to the heart tissues exposed to hypoxia, which possibly led to inhibition of apoptosis. This suggests that MGF may play a dual role in cardiac function, acting as a potential anti-apoptotic compound and a stem cell-homing factor. The researchers highlight that MGF potentially enhances the migration of mesenchymal stem cells (hMSCs), indicating a chemotactic action that might be leveraged to direct stem cells toward regions of damage or injury. Moreover, in an environment simulating hypoxic stress—a condition akin to that experienced by heart tissue during ischemic events—MGF is suggested to exhibit protective potential in cardiac cells. This hypothesis was raised by observation of increases in the expression of Bcl-2, a gene associated with cell survival, underscoring MGF's potential anti-apoptotic action. MGF Peptide and Skeletal Injury The main goal of this study(11) was to evaluate the potential of MGF on bone injury. A total of 27 rabbits were experimentally induced with a 5-mm bone defect and were then divided into three groups that were presented with MGF or with a control substance for 5 consecutive days. Post-study, the researchers reported that the placebo tissue appeared to be the least healed when the bone tissues were histologically examined. In contrast, the bone tissue with MGF appeared to be the most healed tissue. Regarding the potential impact on osteoblast-like cell proliferation, the investigation hints that MGF might potentially enhance proliferation. This enhancement appears to be more pronounced when compared with IGF-1, leading to the speculation that MGF may activate cellular mechanisms somewhat differently from IGF-1. The study points out that MGF might play a role in arresting the cell cycle in certain phases and could be involved in activating the MAPK-Erk1/2 signaling pathway. Such actions imply that MGF may have a complex approach to promoting cell proliferation, perhaps through a blend of influencing cell cycle dynamics and engaging specific signaling pathways. Moreover, the study ventured into assessing the possible actions of MGF utilizing a rabbit model with established bone defects. Here, MGF was introduced, and its influence on bone healing was monitored via radiographic and histological evaluations. The findings tentatively indicate that bone healing might be improved in defects exposed to MGF, as suggested by seemingly better rates of radiographically healed defects and improved histological scores for bone healing. MGF Peptide and Brain Ischemia The main purpose of a 2005 study(12) was to combat ischemic stroke through the potential action of MGF peptides. The actions were studied in experiments conducted on gerbil research models of brain ischemia. The synthetic Mechano Growth Factor peptide was presented as an ischemic mitigator. Researchers reported that MGF appeared to lead to increased protection of brain cells. Interestingly, in the same model, it was also reported that ischemia appeared to lead to elevated endogenous MGF production in the ischemia-resistant neurons. Additional studies were carried out in degenerated hippocampal cell culture, to which MGF was added. MGF exhibited reportedly similar results of muscle proliferation. This potential action is believed to be due to the C-terminal of the MGF peptide, which may exert some level of neuroprotective action. MGF Peptide and Brain Cells A notable study (13) was conducted on a murine model to study the action of increased MGF concentration on brain cells. One study included breeding mice to constitutively overproduce MGF in the hippocampus area of the brain. The hippocampus is primarily responsible for regulating the neurogenesis phenomenon in the organism. This overproduction of MGF appeared to result in high concentrations of BrdU, a biological marker representative of proliferative actions in the organism. More specifically, the mice were bred for conditional MGF production at 1, 3, and 12 months old. Behavioral analysis and biological responses were examined after 2 years. These mice were reported to exhibit elevated levels of BrdU and neurogenesis. MGF peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Philippou A, Papageorgiou E, Bogdanis G, Halapas A, Sourla A, Maridaki M, Pissimissis N, Koutsilieris M. Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro. In Vivo. 2009 Jul-Aug;23(4):567-75. https://pubmed.ncbi.nlm.nih.gov/19567392/ Goldspink G. Impairment of IGF-I gene splicing and MGF expression associated with muscle wasting. Int J Biochem Cell Biol. 2006 Mar;38(3):481-9. https://pubmed.ncbi.nlm.nih.gov/16463438/ Zabłocka, B., Goldspink, P. H., Goldspink, G., & Górecki, D. C. (2012). Mechano-Growth Factor: an important cog or a loose screw in the repair machinery? Frontiers in endocrinology, 3, 131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485521/ G Goldspink. Research on mechano growth factor: its potential for optimising physical training as well as misuse in doping. Department of Surgery, Royal Free and University College Medical School, Hampstead Campus, Rowland Hill Street, London NW3 2PF. https://bjsm.bmj.com/content/39/11/787 Rotwein P. (2014). Editorial: the fall of mechanogrowth factor?. Molecular endocrinology (Baltimore, Md.), 28(2), 155–156. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896639/ Mills P, Dominique JC, Lafrenière JF, Bouchentouf M, Tremblay JP. A synthetic mechano growth factor E Peptide enhances myogenic precursor cell transplantation success. Am J Transplant. 2007 Oct;7(10):2247-59. https://pubmed.ncbi.nlm.nih.gov/17845560/ Hameed M, Lange KH, Andersen JL, Schjerling P, Kjaer M, Harridge SD, Goldspink G. The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men. J Physiol. 2004 Feb 15;555(Pt 1):231-40. doi: 10.1113/jphysiol.2003.051722. Epub 2003 Oct 17. PMID: 14565994; PMCID: PMC1664832. Kandalla PK, Goldspink G, Butler-Browne G, Mouly V. Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages. Mech Ageing Dev. 2011 Apr. https://pubmed.ncbi.nlm.nih.gov/21354439/ Liu X, Zeng Z, Zhao L, Chen P, Xiao W. Impaired Skeletal Muscle Regeneration Induced by Macrophage Depletion Could Be Partly Ameliorated by MGF Injection. Front Physiol. 2019 May 17;10:601. https://pubmed.ncbi.nlm.nih.gov/31164836/ Doroudian, G., Pinney, J., Ayala, P., Los, T., Desai, T. A., & Russell, B. (2014). Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes. Biomedical microdevices, 16(5), 705–715. https://doi.org/10.1007/s10544-014-9875-z Deng M, Zhang B, Wang K, Liu F, Xiao H, Zhao J, Liu P, Li Y, Lin F, Wang Y. Mechano growth factor E peptide promotes osteoblasts proliferation and bone-defect healing in rabbits. Int Orthop. 2011 Jul;35(7):1099-106. https://pubmed.ncbi.nlm.nih.gov/21057789/ Dluzniewska J, Sarnowska A, Beresewicz M, Johnson I, Srai SK, Ramesh B, Goldspink G, Górecki DC, Zabłocka B. A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia. FASEB J. 2005 Nov;19(13):1896-8. https://pubmed.ncbi.nlm.nih.gov/16144956/ Tang JJ, Podratz JL, Lange M, Scrable HJ, Jang MH, Windebank AJ. Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain. Mol Brain. 2017 Jul 7;10(1):23. doi: 10.1186/s13041-017-0304-0. PMID: 28683812; PMCID: PMC5501366. Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Syn-Coll (Palmitoyl Tripeptide-5) (200mg)
Syn-Coll is a synthetic peptide compound, also known as palmitoyl tripeptide-5. It was designed to mimic the activity of thrombospondin-1 (TSP-1), a natural extracellular matrix protein that apparently stimulates transforming growth factor beta (TGF-β). TGF-β is a crucial growth factor that plays a vital role in maintaining skin integrity and stimulating the postnatal development of skin structures by promoting collagen synthesis. The short sequence Lys-Arg-Phe-Lys of TSP-1 is considered responsible for TGF-β stimulation.(1) Syn-Coll has the sequence of Palmitoyl-Lys-Val-Lys, and scientists report that it may exert similar action on TGF-β. As a result, animal models and dermal fibroblasts cell culture tests suggest it may stimulate collagen production. More specifically, Syn-Coll may increase the production of Type I and Type III collagen by dermal fibroblasts via stimulating TGF-β activity. Furthermore, Syn-Coll has been extensively studied in animal models and experiments, which all generally hypothesize that it exhibits some potential to increase collagen synthesis but also prevent collagen degradation. Syn-Coll may prevent collagen breakdown by inhibiting the activity of matrix metalloproteinases (MMPs) such as MMP1 and MMP3. Chemical Makeup Molecular Formula: C33H65N5O5 Molecular Weight: 611.9 g/mol Other Known Titles: Palmitoyl-lysyl-valyl-lysine, Palmitoyl Tripeptide-5 Research and Clinical Studies Syn-Coll Peptide and Collagen Synthesis Collagen is a major component of the extracellular matrix, the network of proteins and fibers that comprise dermal connective tissue. Recent studies have indicated that Syn-Coll may stimulate collagen synthesis. This synthetic peptide is believed to work by mimicking the activity of TSP-1 to activate the growth factor TGF-β. More specifically, Syn-Coll may work by mimicking part of the sequence of TSP-1.(2) TGF-β is a crucial growth factor that has been suggested to play an important role in regulating collagen production. Studies have suggested that Syn-Coll works by activating latent TGF-β, thereby increasing the production of type I and type III collagen by dermal fibroblasts. As a result, scientists report that activating TGF-β "causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal [...] dermal fibroblasts."(3) Trials have also indicated that Syn-Coll may increase type 1 collagen synthesis via TGF-β to a greater degree than other peptides, such as palmitoyl pentapeptide.(4) The researchers posited that "Palmitoyl tripeptide-5 also known as Syn-Coll, increases collagen 1 production via TGF-b reportedly 60% more effective than palmitoyl pentapeptide." Syn-Coll Peptide and Collagen Breakdown Matrix metalloproteinases (MMPs) are a group of enzymes involved in the degradation of extracellular matrix proteins, including collagen. Scientists consider MMPs to be typically produced by dermal cells, such as fibroblasts, and are involved in tissue remodeling and maintaining the extracellular matrix. However, they further posit when MMPs are overproduced or become dysregulated, they can contribute to dermal collagen breakdown. For example, MMP-1 is considered to be an enzyme that specifically degrades type I collagen. Fibroblasts produce MMP-1, and its activity may be increased by factors such as UV radiation, inflammation, and oxidative stress. Another member of the MMPs is MMP-3, and considered capable of cleaving a wide range of extracellular matrix proteins, including collagens, laminin, fibronectin, proteoglycans, and elastin. It may be particularly active at degrading type II collagen, the main structural component of cartilage. MMP-3 has also been implicated in the degradation of other collagens, such as type III collagen, which is abundant in the skin and blood vessels. Syn-Coll (Palmitoyl tripeptide-5) seems to decrease collagen breakdown by inhibiting matrix metalloproteinases degrading collagen. More specifically, studies suggest that Syn-Coll (palmitoyl tripeptide-5) may prevent collagen breakdown by interfering with MMP1 and MMP3 collagen degradation.(5) Syn-Coll Peptide and Anti-Aging Studies have suggested that Syn-Coll may reduce the appearance of wrinkles to a much greater extent than a placebo.(6) The scientists reported that "formulation demonstrated a dose-dependent wrinkle reduction, measured by PRIMOS surface topography." Ultimately, they concluded that Syn-Coll (palmitoyl tripeptide-5) might exhibit roughly 3.5 times the potential to reduce the appearance of wrinkles than the placebo. One study in 60 test subjects that lasted 84 days reported that Syn-Coll twice daily suggested it may exhibit anti-wrinkle potential and reduce skin roughness better than control groups, placebo, and other peptides.(7) The peptide appeared to reduce wrinkle parameters by 12%. Besides its potential on collagen synthesis and degradation, scientists suggest that Syn-Coll may exert possible anti-wrinkle action through other mechanisms.(8) These include supporting the skin's barrier function by possibly preventing water loss from the skin's surface. This can help to maintain optimal hydration levels in the skin. Furthermore, Syn-Coll may act as a humectant, which can help absorb and retain water in the skin. It may also increase skin surface lipids and act as an emollient, providing partial occlusion, lubrication, and moisturization to the skin. In addition, Syn-Coll may also be modified by adding an L-ascorbate moiety (AA) at the C-terminus (Pal-KVK-AA), which may have a depigmentation impact. Studies have suggested that this conjugation may inhibit melanin synthesis.(9) By blocking melanin production, this modified version of Syn-Coll may help reduce hyperpigmentation caused by photoaging, UV light, oxidative stress, and other factors. Syn-Coll peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Murphy-Ullrich, J. E., & Poczatek, M. (2000). Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine & growth factor reviews, 11(1-2), 59–69. https://doi.org/10.1016/s1359-6101(99)00029-5 Trookman, N. S., Rizer, R. L., Ford, R., Ho, E., & Gotz, V. (2009). Immediate and Long-term Clinical Benefits of a Treatment for Facial Lines and Wrinkles. The Journal of clinical and aesthetic dermatology, 2(3), 38–43. Varga, J., Rosenbloom, J., & Jimenez, S. A. (1987). Transforming growth factor beta (TGF beta) causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts. The Biochemical journal, 247(3), 597–604. https://doi.org/10.1042/bj2470597 Bucay, V. W., & Day, D. (2013). Adjunctive skin care of the brow and periorbital region. Clinics in plastic surgery, 40(1), 225–236. https://doi.org/10.1016/j.cps.2012.09.003 Errante, F., Ledwoń, P., Latajka, R., Rovero, P., & Papini, A. M. (2020). Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Frontiers in chemistry, 8, 572923. https://doi.org/10.3389/fchem.2020.572923 Gorouhi, F., & Maibach, H. I. (2009). Role of peptides in preventing or treating aged skin. International journal of cosmetic science, 31(5), 327–345. https://doi.org/10.1111/j.1468-2494.2009.00490.x Schneider, A. L. (2010). Evaluation of the penetration and efficacy of anti-aging compounds (Doctoral dissertation, Monash University). Kim, H. M., An, H. S., Bae, J. S., Kim, J. Y., Choi, C. H., Kim, J. Y., Lim, J. H., Choi, J. H., Song, H., Moon, S. H., Park, Y. J., Chang, S. J., & Choi, S. Y. (2017). Effects of palmitoyl-KVK-L-ascorbic acid on skin wrinkles and pigmentation. Archives of dermatological research, 309(5), 397–402. https://doi.org/10.1007/s00403-017-1731-6 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.
Vilon (20mg)
Vilon is a dipeptide composed of amino acids lysine and glutamic acid. It also goes by the name 'Lysylglutamic Acid or Lysylglutamate.'(1) It is the shortest peptide suggested to possess potential action in the immune system, possibly mitigate cancer cell proliferation, and potentially induce anti-aging action within cells, possibly working on tissues within the liver, heart, and kidney. Vilon appears to exert its potential by possible interaction with the chromatin structure. Vilon peptide research has also led to the postulating of several research hypotheses, including that the peptide may act to unroll chromatin structures, that it may activate ribosomal genes stimulating the synthetic process, that it may release inactive genes, and that it may not decondense the chromatin situated on each side of the centromere of the chromosome. Through its potential action on the chromatin, Vilon may possibly alter DNA structure to reactivate the genes and cells that have gone 'silent.' Overview Considered a bioregulator peptide, researchers speculate that Vilon may potentially support functions within the immune system, including in immunocompromised animal models. Researchers suggest Vilon may activate the interleukin-2 protein in spleen cells, which is considered critical in maintaining immune function.(3) It may stimulate the organism to fight against microbial infection and foreign bodies and prevent harmful autoimmune responses. Vilon has been suggested to activate white blood and spleen cells and potentially naturally boost the organism to protect against autoimmune elements. A study was conducted in 2002 with three bioregulatory peptides to study their potential on interleukin-2 mRNA synthesis in spleen cells. According to this study, “The intensity of interleukin-2 mRNA synthesis in splenocytes depended on the type, concentration, and duration of [exposure] with the peptides. Vilon and Epithalon were most potent, while Cortagen produced a less pronounced effect on interleukin-2 mRNA synthesis.”(3) Furthermore, research suggests that Vilon peptides may possibly mitigate autoimmune action by interacting with the thymus gland. The thymus gland is considered responsible for the proliferation of T-helper cells, and with the help of the Vilon peptide, this proliferation may be further enhanced. As per N N Sevostianiva et al., the Vilon peptide is “considered as a bioactive substance possessing immunomodulator and antiallergic activity.” (4) The research indicates that there is a potential for Vilon to enhance the expression of the CD5 molecule in embryonic thymic cells. Specifically, the data revealed a tentative increase of 78% in the expression levels of CD5 in rat thymic cells and a 45% increase in embryonic thymic cells compared with the baseline levels in the control group. CD5 is a marker important in the development and maturation of T-cells in the thymus, an organ considered pivotal for the generation of immune cells. The study further hypothesizes that Vilon may influence the maturation process of thymic cells, potentially steering the development of T-cell precursors more toward becoming CD4+ T-helper cells. T-helper cells are deemed critical components of the adaptive immune system, aiding in the activation and direction of other immune cells. Chemical Makeup Molecular formula: C11H21N3O5 Molecular weight: 257.30g/mol Other known titles: Lysylglutamate, normophthal, Lysylglutamic acid Vilon Research and Clinical Studies Extended research has produced a wide variety of hypotheses speculating on the action of the Vilon peptide, some detailed below: Vilon Peptide and Cellular Lifespan Vilon may potentially extend the average lifespan of certain animal models under laboratory conditions through an extension and mitigation of cell death. As stated above, Vilon has been suggested to exhibit potential in enhancing the immune system, improving physical endurance and energy levels, thereby possibly increasing average lifespan of animal test models.(5) Vilon is advised to study earlier in the test model lifespan rather than later for clearest possible action. Researchers hypothesize when a bioregulator like Vilon is exposed in vivo in lab models, it may only reverse 'silent' cells, exerting no apparent action on cells killed via apoptosis. In another experiment, researchers explored the potential of Vilon on spleen organotypic tissue cultures derived from murine models of differing ages. The findings from this investigation suggest that Vilon potentially influences the development of the explants.(6) Further research investigated research models where the peptide was introduced into the cultural medium of tissue explants derived from murine models at varying stages of development: 3 days, 3 weeks, and 2 years old. It was posited that Vilon induces morphological stability in the tissues while potentially activating both regeneration and functional activity of the cells involved. Interestingly, the results suggest that the impact of Vilon appeared to be more pronounced in explants from older murine models. This observation leads to the hypothesis that Vilon may have potential relevance in geriatric research, focusing on the mechanisms of cell aging and regeneration. The possibility that Vilon preferentially supports older tissues might be indicative of its role in modulating age-related cellular mechanisms or promoting stability in more senescent cells.(7) Another study examined the actions of low amounts of ionizing radiation, which apparently leads to accelerated cell aging of the thymus and spleen in murine models. Vilon was tested for its potential to mitigate this accelerated cellular aging process. The researchers tentatively suggest that Vilon partially inhibited the pro-aging action induced by the radiation. This research posits that Vilon might be of interest in the field of geriatric research, potentially as an agent to manage or reduce the impacts of cell aging in critical immune organs post-radiation exposure. The study highlights Vilon’s potential role in preserving organ function in an irradiated environment, which may be crucial for developing strategies against radiation-induced degeneration in murine models.(8) Vilon Peptide and Carcinogenic Cells Several studies suggest that peptide exhibits the potential to prevent some spread of carcinogenic cells by preventing the formation of new tumors, and potentially inhibiting existing tumors' growth.(9) Another study examined the potential of Vilon on the development of urinary bladder carcinogenesis in murine models exposed to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBNA).(10) The experiment included a control group and a Vilon-exposed group. Each group began with 50 rats, all of which received BBNA. The primary observation was that the incidence of urinary bladder cancer cells was lower in the Vilon-exposed group compared to the control group. Specifically, cancer cells developed in 56% of the Vilon-exposed murine models versus 75.5% of the controls. This data possibly indicates that Vilon may have a moderating action on cancer cell development when exposed to BBNA. Further, the study noted a reduction in both the prevalence and severity of preneoplastic and early neoplastic changes in the urinary bladder mucosa in the Vilon-exposed murine models. In terms of morphological changes, the study reported fewer hyperplastic changes and lower malignancy rates in the Vilon group. There was a noticeable delay in the malignization of epithelial tissues in the Vilon group, suggesting a potential role of Vilon in modulating the rate or extent of tumor malignancy. Additionally, the average number of tumors per animal was lower in the Vilon group (1.5 tumors per rat) compared to the control group (2.6 tumors per rat), and the tumor cells in the Vilon-exposed rats appeared to manifest with a less aggressive growth pattern. The reduction in tumor aggressiveness and prevalence might indicate that Vilon has the potential to modulate the carcinogenic actions of BBNA. The findings suggest that Vilon, potentially acting as an immunomodulator, might inhibit the early stages of carcinogenesis as well as tumor progression in experimental models. One study contradicts this potential property of Vilon. According to this study, when used with chemotherapeutic agents derived from platinum ions, this peptide–platinum combination may be more harmful than helpful.(11) Unfortunately, since this study only considers one specific type of chemotherapeutic action, the results reported by researchers may be inconclusive. Vilon Peptide and the Gastrointestinal Tract Vilon peptide may act on gastrointestinal functionality by possibly enhancing the working mechanisms of certain enzymes in the gastrointestinal tract. By doing so, the peptide exhibits potential resistance towards GI-specific ailments, and may reduce leaky bowels in animal models.(12) Acting on the small intestinal muscles, Vilon peptide may ameliorate glucose accumulation and glycine absorption.(13) Vilon Peptide and Gene Expression Upon presenting the Vilon peptide, researchers have suggested it exhibits potential to alter the gene expression of 36 genes in the heart. When presented with Epitalon, this number was reported as 144 genes. This suggests the peptide's possible action on genetic expression in the cardiac system, possibly impacting hemodynamic actions.(14) Vilon Peptide and Fibrinolysis Researchers suggested in one study that Vilon exhibits the potential to stimulate fibrinolysis and increase the concentration of natural anticoagulants in the organsim, namely antithrombin III and protein C. It was also suggested to reduce insulin levels and possibly regulate the metabolism of carbohydrates.(15) This suggests a possible interplay between Vilon's actions on coagulation and glucose regulation, although the mechanisms behind this interaction are not fully elucidated in the study. Furthermore, the study posits that Vilon may have a stabilizing impact on the immune system. This is inferred from changes in various immune cell types and immunoglobulins; notably, a reduction in T-helpers, T-dependent and non-T-dependent NK cells, and a normalization in the levels of active T-lymphocytes, B-lymphocytes, and IgA. Such findings suggest that Vilon may modulate both innate and adaptive immune responses, which may be crucial for overall immune homeostasis. Further, Vilon is suggested to increase the permeability of mesenteric microvessels in the vascular system. As per N. Gavrisheva et al., these results indicate that “the preparation produces a potent homeostatic effect in the early period of chronic renal failure.”(16) Vilon peptide 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 (2022). PubChem Compound Summary for CID 7010502, Lysylglutamic acid. Retrieved November 21, 2022 from https://pubchem.ncbi.nlm.nih.gov/compound/Lysylglutamic-acid Lezhava T, Khavison V, Monaselidze J, Jokhadze T, Dvalishvili N, Bablishvili N, Barbakadze S. Bioregulator Vilon-induced reactivation of chromatin in cultured lymphocytes from old people. Biogerontology. 2004;5(2):73-9. https://pubmed.ncbi.nlm.nih.gov/15105581/ Kazakova TB, Barabanova SV, Khavinson VKh, Glushikhina MS, Parkhomenko EP, Malinin VV, Korneva EA. In vitro effect of short peptides on expression of interleukin-2 gene in splenocytes. Bull Exp Biol Med. 2002 Jun;133(6):614-6. https://pubmed.ncbi.nlm.nih.gov/12447482/ Sevostianova NN, Linkova NS, Polyakova VO, Chervyakova NA, Kostylev AV, Durnova AO, Kvetnoy IM, Abdulragimov RI, Khavinson VH. Immunomodulating effects of Vilon and its analogue in the culture of human and animal thymus cells. Bull Exp Biol Med. 2013 Feb;154(4):562-5. English, Russian. https://pubmed.ncbi.nlm.nih.gov/23486604/ Khavinson VK, Anisimov VN, Zavarzina NY, Zabezhinskii MA, Zimina OA, Popovich IG, Shtylik AV, Malinin VV, Morozov VG. Effect of vilon on biological age and lifespan in mice. Bull Exp Biol Med. 2000 Jul;130(7):687-90. DOI: 10.1007/BF02682106. PMID: 11140587. https://pubmed.ncbi.nlm.nih.gov/11140587/ Bykov NM, Chalisova NI. Osobennosti deĭstviia ul'tramalykh doz vilona v organotipicheskoĭ kul'ture selezenki krys raznogo vozrasta [Characteristics of effect of ultralow doses of vilon in organotypic culture of spleens from rats of various ages]. Adv Gerontol. 2002;10:85-7. Russian. PMID: 12577696. Kniaz'kin IV, Iuzhakov VV, Chalisova NI, Grigor'ev EI. Funktsional'naia morfologiia organotipicheskoĭ kul'tury selezenkoi krys razlichnogo vozrasta pri deĭstvii vilona [Functional morphology of organotypic culture of spleens from rats of various ages exposed to vilon]. Adv Gerontol. 2002;9:110-5. Russian. PMID: 12096432. Kniaz'kin IV, Poliakova VO. Deĭstvie vilona na timus i selezenku v radiatsionnoĭ modeli prezhdevremennogo stareniia [The effect of vilon on the thymus and spleen in a radiation model of premature aging]. Adv Gerontol. 2002;9:105-9. Russian. PMID: 12096431. Khavinson VKh, Anisimov VN. A synthetic dipeptide vilon (L-Lys-L-Glu) inhibits the growth of spontaneous tumors and increases the life span of mice. Dokl Biol Sci. 2000 May-Jun;372:261-3. PMID: 10944717. https://pubmed.ncbi.nlm.nih.gov/10944717/ Pliss GB, Mel'nikov AS, Malinin VV, Khavinson VK. Inhibitory effect of peptide vilon on the development of induced rat urinary bladder tumors in rats. Bull Exp Biol Med. 2001 Jun;131(6):558-60. doi: 10.1023/a:1012354603132. PMID: 11586406. Barykina OP, Iuzhakov VV, Chalisova NI, Kvetnoĭ IM, Konovalov SS. Sochetannoe vliianie vilona i tsiklofosfana na transplanty opukholeĭ i éksplantaty limfoidnoĭ tkani mysheĭ i krys raznogo vozrasta [Combined effect of vilon and cyclophosphane on tumor transplants and lymphoid tissue explants in mice and rats of various age]. Adv Gerontol. 2003;12:128-31. Russian. PMID: 14743610. https://pubmed.ncbi.nlm.nih.gov/14743610/ Khavinson VKh, Timofeeva NM, Malinin VV, Cordova LA, Nikitina AA. Effect of vilon and epithalon on activity of enzymes in epithelial and subepithelial layers in small intestine of old rats. Bull Exp Biol Med. 2002 Dec;134(6):562-4. https://pubmed.ncbi.nlm.nih.gov/12660839/ Khavinson VKh, Egorova VV, Timofeeva NM, Malinin VV, Cordova LA, Gromova LV. Effect of Vilon and Epithalon on glucose and glycine absorption in various regions of small intestine in aged rats. Bull Exp Biol Med. 2002 May;133(5):494-6. https://pubmed.ncbi.nlm.nih.gov/12420071/ Anisimov SV, Bokheler KR, Khavinson VKh, Anisimov VN. Studies of the effects of Vilon and Epithalon on gene expression in mouse heart using DNA-microarray technology. Bull Exp Biol Med. 2002 Mar;133(3):293-9. https://pubmed.ncbi.nlm.nih.gov/12360356/ Kuznik BI, Isakova NV, Kliuchereva NN, Maleeva NV, Pinelis IS. [Effect of vilon on the immunity status and coagulation hemostasis in patients of different age with diabetes mellitus]. Adv Gerontol. 2007;20(2):106-15. Russian. PMID: 18306698. https://pubmed.ncbi.nlm.nih.gov/18306698/ Gavrisheva NA, Malinin VV, Ses TP, Kozlov KL, Panchenko AV, Titkov AY. Effect of peptide Vilon on the content of transforming growth factor-beta and permeability of microvessels during experimental chronic renal failure. Bull Exp Biol Med. 2005 Jan;139(1):24-6. DOI: 10.1007/s10517-005-0202-9. PMID: 16142267. https://pubmed.ncbi.nlm.nih.gov/16142267/ 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.
Sermorelin & Ipamorelin Blend (10mg)
Both Ipamorelin & Sermorelin are synthetic peptides, and when blended, they may act synergistically to further their individual potential impacts. More specifically, they both appear to upregulate the production of growth hormone. The growth hormone appears to play a vital role in accelerating growth and is considered to function primarily to regulate metabolic functions. Overview Sermorelin & Ipamorelin are synthetic peptides, where Sermorelin is composed of 29 amino acids(1) and Ipamorelin is composed of 5 amino acids.(2) Sermorelin seems to serve as a functional equivalent to the naturally occurring growth hormone-releasing hormone (GHRH). Unlike GHRH, which consists of 44 amino acids, Sermorelin is shortened to a sequence of 29 amino acids. This truncated form is also referred to as Growth Hormone Releasing Factor (1-29) or simply GRF (1-29). Ipamorelin was the first synthetic GHS discovered with a proposed high selectivity towards the growth hormone receptors without apparently affecting the synthesis of other pituitary hormones such as ACTH and prolactin.(3) Sermorelin is also known as GHRF (1-29) amide, and the potential of this fragment was first investigated in the early 1980s. It was suggested that upon introduction, Sermorelin may exhibit affinity towards the GHRH receptors located at the pituitary gland and possibly stimulate the secretion of growth hormone.(4) Both Ipamorelin & Sermorelin are posited to produce action on the pituitary gland. Upon binding, these peptides are suggested to stimulate the pituitary gland and secrete more growth hormone.(4)(5) The difference in their mode of action is the pathway by which they exert their action. Sermorelin appears to affect the GHRH receptors while Ipamorelin appears to act via the ghrelin pathway.(5) Thus, it is believed that Sermorelin may retain the core ability of GHRH: to potentially prompt the GHRH receptors in the pituitary gland to intermittently release growth hormone. This action is thought to subsequently elevate levels of insulin-like growth factor-1 (IGF-1), which is viewed as the primary agent responsible for the anabolic action of growth hormone. Ipamorelin does not appear to work via the GHRH receptors. Instead, this synthetic pentapeptide is under investigation for its potential capabilities as a growth hormone secretagogue (GHS). It is thought to function similarly to Growth Hormone Releasing Peptides (GHRPs) and may potentially mimic the natural action of the hunger hormone, ghrelin. The peptide is suspected to target ghrelin receptors in the anterior pituitary gland, also known as Growth Hormone Secretagogue Receptors 1 Alpha (GHS-R1a). This characteristic positions Ipamorelin as a highly selective secretagogue and a potent agonist for the growth hormone/ghrelin secretagogue receptor. Since the mode of action of both the peptides appears to be different, they may complement each other when presented together and thereby provide a potentially greater growth hormone response. A major difference between the two peptides appears to be their respective half-lives, where the half-life of Sermorelin is considered to be 11 to 12 minutes and that of Ipamorelin is approximately 2 hours.(6) Therefore, research has posited that Sermorelin may trigger an immediate growth hormone response while Ipamorelin may extend this process for longer periods. Chemical Makeup Molecular Formula: Sermorelin: C149H246N44O42S Ipamorelin: C38H49N9O5 Molecular Weight: Sermorelin: 3357.93 g/mol Ipamorelin: 771.86 g/mol Other Known Titles Sermorelin: GRF 1-29 Ipamorelin: NNC 26-0161 Research and Clinical Studies Currently, there is no research and clinical data available for the Ipamorelin & Sermorelin blend together, however both these peptides have been individually studied. Sermorelin & Ipamorelin Blend and Growth Hormone Sermorelin and ipamorelin are both peptides that have been investigated for their possible roles in elevating levels of growth hormone and its potential anabolic mediator, IGF-1. One study seems to suggest that Sermorelin may lead to an 82% increase in average growth hormone levels, which appeared to last for around two hours.(7) Another study, lasting 16 weeks, posited that Sermorelin might potentially result in up to a 107% rise in growth hormone levels and up to a 28% uptick in IGF-1 levels.(8 Conversely, Ipamorelin has been associated with what appears to be a substantial increase in growth hormone levels, reaching levels that may be as high as 80mIU/l (approximately a 26.6ng/ml concentration). When these figures are presented as a percentage increase compared to a placebo (1.31mIU/l (0.4ng/ml)), it seems to represent a noteworthy elevation in growth hormone levels, exceeding 6000%. Both peptides appear to have a strong potential for raising growth hormone and IGF-1 levels. However, it is worth noting that the extent of the increase and the duration for which these elevated levels are maintained could vary between the two.(9 Sermorelin & Ipamorelin Blend and Lean Mass Both Sermorelin and Ipamorelin appear to exert influence on lean mass and body composition. According to research, Sermorelin has been suggested to increase lean body mass by a margin of 2.78 lbs (1.26 kg), without affecting fat mass. These observations are posited to be due to the potential of the peptide to increase growth hormone and subsequently IGF-1, a purported anabolic mediator of growth hormone.(8) The most notable results commented by the researchers included that “...a gain of 1.26 ± 0.52 kg (P < 0.05) in LBM was found.” and “Skin thickness increased significantly…” Ipamorelin has also been suggested to potentially lead to lean mass increase, related to an increase in appetite and total weight gain. That is related to the proposed impact that Ipamorelin may have on ghrelin receptors. For instance, research suggests that subjects exposed to Ipamorelin exhibited a weight increase by roughly 17%.(10) The compound is thought to potentially elevate fat pad weights in proportion to total body mass. Consequently, measurements taken via dual energy X-ray absorptiometry (DEXA) might indicate a relative increase in body fat. Moreover, there are indications that Ipamorelin may have elevated serum leptin levels, a hormone involved in energy and appetite regulation. The researchers posited that “GHSs increase body fat by GH-independent mechanisms that may include increased feeding.” This has led experts to speculate that heightened food consumption may contribute to the observed weight gain in groups presented with Ipamorelin. Sermorelin & Ipamorelin Blend and Bone Mineralization Ipamorelin has been purported to potentially cause an increase in bone mineral density which may be related to its apparent role in increasing lean and total weight. During an investigation, Ipamorelin and a placebo were tested on mouse models to evaluate their action on bone density.(11) The study utilized real-time DEXA scans to track alterations in bone mineral content, with a focus on specific areas such as the femur and L6 vertebrae. Once the study concluded, pQCT scans were performed on the femurs to gather additional data. Preliminary results suggest a potential correlation between Ipamorelin and both weight gain and an increase in bone mineral content in the tibia and vertebrae, as evidenced by DEXA, relative to the placebo group. Furthermore, the pQCT findings hint that the noted increase in cortical BMC could be due to an expansion in the bone's cross-sectional area. Sermorelin & 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. “PubChem Compound Summary for CID 16129620, Sermorelin” PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Sermorelin National Center for Biotechnology Information. “PubChem Compound Summary for CID 9831659, Ipamorelin” PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Ipamorelin 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. https://pubmed.ncbi.nlm.nih.gov/9849822/ Clark, R G, and I C Robinson. “Growth induced by pulsatile infusion of an amidated fragment of human growth hormone releasing factor in normal and GHRF-deficient rats.” Nature vol. 314,6008 (1985): 281-3. https://pubmed.ncbi.nlm.nih.gov/2858818/ 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 Junichi I. et al, Growth hormone secretagogues: history, mechanism of action, and clinical development, JSCM Rapid Communications Vol. 3 Issue 1, 09 February 2020. https://onlinelibrary.wiley.com/doi/full/10.1002/rco2.9 Vittone, J., Blackman, M. R., Busby-Whitehead, J., Tsiao, C., Stewart, K. J., Tobin, J., Stevens, T., Bellantoni, M. F., Rogers, M. A., Baumann, G., Roth, J., Harman, S. M., & Spencer, R. G. (1997). Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism: clinical and experimental, 46(1), 89–96. https://doi.org/10.1016/s0026-0495(97)90174-8 Khorram, O., Laughlin, G. A., & Yen, S. S. (1997). Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. The Journal of clinical endocrinology and metabolism, 82(5), 1472–1479. https://doi.org/10.1210/jcem.82.5.3943 Gobburu, J. V., Agersø, H., Jusko, W. J., & Ynddal, L. (1999). Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharmaceutical research, 16(9), 1412–1416. https://doi.org/10.1023/a:1018955126402 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.
Bronchogen (20mg)
Bronchogen, also known as AEDL, is classified among the Khavinson peptides and is has been suggested by researchers to act as a bioregulator. These are short signaling peptides which may cross through cellular and nuclear membranes to directly interact with the DNA. Bronchogen may have specific affinity for lung cells by regulating the expression of the NKX2-1, SCGB1A1, SCGB3A2, FOXA1, and FOXA2 genes.(1) Furthermore, authors comment that it may “bind preferentially with deoxyribooligonucleotides containing CNG sequence (CNG sites are targets for cytosine DNA methylation in eukaryotes).”(2) Indeed, the peptide has been suggested to potentially attenuate inflammatory reactions in the lungs of murine models with bleomycin-induced fibrosis(3) Chemical Makeup Molecular formula: C18H30N4O9 Molecular weight: 446.45 g/mol Sequence: Ala-Glu-Asp-Leu Other known titles: AEDL Research and Clinical Studies Below we have delved deep into the latest clinical and preclinical data on the potential actions of Bronchogen as seen in various research models. Bronchogen and DNA Studies have suggested that the peptide may interact with “lung cells by regulating the expression of the NKX2-1, SCGB1A1, SCGB3A2, FOXA1, and FOXA2 genes” to exert its potential actions on DNA. These actions may include reducing inflammation, promoting differentiation and preventing remodeling. (1) (4) Further, Bronchogen’s interaction with DNA may affect genetic expression. The interaction between Bronchogen and deoxyribooligonucleotides (short DNA segments) containing a CNG sequence may potentially influence gene regulation and expression due to its association with cytosine DNA methylation sites. In eukaryotes, CNG sites (where "C" denotes cytosine, "N" stands for any nucleotide including A, T, G, or C, and "G" signifies guanine) are common targets for DNA methylation, which is considered to play a pivotal role in epigenetic modulation. Methylation at cytosine residues, particularly at CpG dinucleotides, is associated with gene silencing. If Bronchogen preferentially binds to these CNG sites, it may interfere with or modulate the methylation process, thereby impacting gene expression. This interaction may influence cellular differentiation and development or alter normal cellular functions.(2) Bronchogen has been suggested to potentially increase DNA thermal stability as well. One study explored the impact of Bronchogen on the thermal stability of DNA derived from calf thymus and mouse liver, employing differential scanning microcalorimetry to analyze thermodynamic parameters during DNA melting. Bronchogen apparently elevated the melting temperature of DNA by 3.1 °C, acting as a DNA-stabilizing agent. The researchers also suggested that Bronchogen may not exhibit base specificity in its binding (non-selective for adenine-thymine or guanine-cytosine pairs), and apparently engages strongly yet sporadically with both DNA strands, primarily interacting with nitrogen bases, which is in contrast with previous suggestions that it targets CNG sites. Potential mechanisms might involve non-covalent interactions, such as hydrogen bonding or van der Waals forces, between Bronchogen and nitrogen bases. The implications of Bronchogen’s potential stabilizing effect on DNA may have relevance in the study and stabilization of DNA structures, possibly aiding in the development of strategies involving nucleic acids, or in biotechnological advancements where enhanced DNA stability is crucial. Further investigations into the structural and molecular aspects of this interaction may unveil more detailed mechanisms.(5) Bronchogen and Cell Renewal Studies suggest that the Bronchogen peptide may impact cell renewal processes and augment the functionality of bronchial epithelial cells, which opens up new potential avenues in cell regeneration research, especially related to bronchial epithelial cells. The specific binding of the peptide to DNA, notably at the guanine N7 site without visibly altering the double-helix structure, indicates a targeted interaction that might be explored further. This suggests that Bronchogen may potentially modulate cellular activities at the genetic level. However, the molecular mechanism through which Bronchogen enhances cell functionality and renewal is not fully detailed yet, making an in-depth investigation into its pharmacodynamics essential to ascertain its potential and to verify that it will not provoke unwanted mutagenic or cytotoxic effects. Furthermore, Bronchogen's potential capability to bind with DNA suggests that it may be utilized in research dedicated to developing targeted delivery systems, where the peptide might be employed to direct other compounds or agents to specific DNA sequences. This interaction and the resulting biological actions need to be extensively studied to establish the potential of Bronchogen in scientific research, considering factors like potential off-target effects, stability, and delivery mechanisms. Ultimately, the researchers commented that the “peptide proved to be an efficient agent stimulating the cell renewal processes and the enhancement of the functional activity of bronchial epithelial cells.”(6) Bronchogen and Inflammation Studies have examined the potential impact of Bronchogen, on the structural and functional aspects of bronchial epithelium, as well as the inflammatory activity within murine models. This model was generated in murine subjects through intermittent exposure to nitrogen dioxide for 60 days which is considered to damage the bronchial epithelium. The bronchial epithelium plays an essential role in guarding against inhaled noxious substances. Bronchogen, by hypothetically modulating inflammatory activity and the bronchial epithelium state in this model, may have led to a reduction in neutrophilic inflammation and normalization of the cellular composition and profile of pro-inflammatory cytokines and enzymes in the bronchoalveolar space. The researchers suggested an apparent structural and functional rejuvenation of the bronchial epithelium, indicated by increased levels of secretory immunoglobulin A, a marker for local immunity, and surfactant protein B, which modulates alveolar surface tension. Possible mechanisms related to these observations may involve Bronchogen intervening in the inflammatory cascade, possibly inhibiting pro-inflammatory cytokines and enzymes, thus alleviating inflammation. Additionally, the peptide might promote regenerative processes in the bronchial epithelium, enhancing its barrier function, and contributing to the balance of surfactant proteins essential for lung function and defenses. This research hints at novel peptide-based strategies for addressing the inflammatory and structural challenges posed by specific respiratory conditions. Further studies, particularly in broader models, are ongoing.(7) Further research suggest that these antiinflammatory actions may be exerted on the bronchial epithelium state to prevent fibrotic changes in the lungs but that the peptide may have potentially beneficial actions in other areas such as minimizing hemodynamic disturbances and possibly reducing myocardial hypertrophy in experimental models.(3) Bronchogen and Tissue Remodeling Trials have investigated the potential of Bronchogen for preventing tissue remodeling in murine models which went through 60-day intermittent exposure to NO2. Bronchogen appeared to abate typical symptoms of bronchial epithelium and lung tissue remodeling, such as goblet cell hyperplasia, squamous metaplasia, lymphocytic infiltration, and emphysema, while also potentially restoring ciliated cells. The researchers commented that there may be an increase in secretory IgA production, indicative of normalized functional activity of bronchial epithelium, and stabilization of cell composition and proinflammatory cytokine profile in the bronchoalveolar space, hinting at reduced neutrophilic inflammation. These outcomes suggest that Bronchogen might alleviate the physical restructuring and dysfunction of lung tissues but also potentially reverse these alterations. The enhanced production of secretory IgA and the modulation of inflammatory markers suggest a mechanism involving immune enhancement and inflammation control.(8) NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering. References: Khavinson, V. K., Popovich, I. G., Linkova, N. S., Mironova, E. S., & Ilina, A. R. (2021). Peptide Regulation of Gene Expression: A Systematic Review. Molecules (Basel, Switzerland), 26(22), 7053. https://doi.org/10.3390/molecules26227053 Fedoreyeva, L. I., Kireev, I. I., Khavinson, V. K.h, & Vanyushin, B. F. (2011). Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA. Biochemistry. Biokhimiia, 76(11), 1210–1219. https://doi.org/10.1134/S0006297911110022 Khavinson, V. K.h, Linkova, N. S., Polyakova, V. O., Kheifets, O. V., Tarnovskaya, S. I., & Kvetnoy, I. M. (2012). Peptides tissue-specifically stimulate cell differentiation during their aging. Bulletin of experimental biology and medicine, 153(1), 148–151. https://doi.org/10.1007/s10517-012-1664-1 Caputi, S., Trubiani, O., Sinjari, B., Trofimova, S., Diomede, F., Linkova, N., Diatlova, A., & Khavinson, V. (2019). Effect of short peptides on neuronal differentiation of stem cells. International journal of immunopathology and pharmacology, 33, 2058738419828613. https://doi.org/10.1177/2058738419828613 Monaselidze, J. R., Khavinson, V. K.h, Gorgoshidze, M. Z., Khachidze, D. G., Lomidze, E. M., Jokhadze, T. A., & Lezhava, T. A. (2011). Effect of the peptide bronchogen (Ala-Asp-Glu-Leu) on DNA thermostability. Bulletin of experimental biology and medicine, 150(3), 375–377. https://doi.org/10.1007/s10517-011-1146-x Morozova, E. A., Lin’kova, N. S., Khavinson, V. K., Soloviev, A. Y., & Kasyanenko, N. A. (2017). In vitro interaction of the AEDL peptide with DNA. Journal of Structural Chemistry, 58, 420-424. Titova, O. N., Kuzubova, N. A., Lebedeva, E. S., Preobrazhenskaya, T. N., Surkova, E. A., & Dvorakovskaya, I. V. (2017). Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova, 103(2), 201–208. Kuzubova, N. A., Lebedeva, E. S., Dvorakovskaya, I. V., Surkova, E. A., Platonova, I. S., & Titova, O. N. (2015). Modulating Effect of Peptide Therapy on the Morphofunctional State of Bronchial Epithelium in Rats with Obstructive Lung Pathology. Bulletin of experimental biology and medicine, 159(5), 685–688. https://doi.org/10.1007/s10517-015-3047-x 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.