Peptides
Fragment 176-191 & CJC-1295 & Ipamorelin Blend (12mg)
Researchers have suggested that growth hormone-releasing peptides (GHRPs), growth hormone secretagogues (GSHs), and analogs of growth hormones (hGH) may exhibit potential to promote growth hormone secretion. When combined, they have been suggested by researchers to exert significant action. These include increased fat metabolism, increased lean mass, regulated sleep cycle, and enhanced intestinal and cardiac functioning. CJC-1295 is a synthetic peptide composed of 29 amino acids. The peptide appears to work by activating the Growth Hormone-Releasing Hormone (GHRH) receptors in the pituitary gland. These receptors are typically activated by the native GHRH. CJC-1295 appears to be a synthetic analog made of the first 29 amino acids from the GHRH sequence, which has additional modifications, including the replacement of four amino acids in its structure and the attachment of a Drug Affinity Complex (DAC) to potentially extend the pharmacokinetics of the peptide. Ipamorelin is a synthetic pentapeptide and has been categorized by scientists as a growth hormone secretagogue (GHS). It has been posited to function similarly to Growth Hormone Releasing Peptides (GHRPs) and to potentially emulate the natural hunger hormone, ghrelin, particularly its potential to stimulate the release of hGH from the cells in the anterior pituitary gland. More specifically, Ipamorelin may mimic the function of ghrelin by activating the ghrelin receptors there, which are also known as the Growth Hormone Secretagogue receptors 1 Alpha (GHS-R1a) Fragment 176-191 peptide, as the name suggests, is a small ‘fragment’ of the growth hormone hGH composed of 15 amino acids. This peptide might target the beta-3 adrenergic receptors (ADRB3), which may potentially induce weight loss downstream. Through these receptors, it is suggested that the peptide may boost fat burning in adipose tissue cells and possibly promote 'thermogenesis' in skeletal muscle cells. Presented together, this blend may trigger a small portion of the pituitary gland, possibly stimulating the release of growth hormones. This blend has been posited by scientists to potentially synergistically enhance and regulate growth hormone concentration and maintain equilibrium levels. Chemical Makeup(1)(2)(3) Molecular formula Fragment 176-191: C78H125N23O23S2 CJC-1295 (Mod GRF 1-29): C152H252N44O42 Ipamorelin: C38H49N9O5 Molecular weight Fragment 176-191: 1817.12 g/mol CJC-1295 (Mod GRF 1-29): 3367.9 g/mol Ipamorelin: 711.8 g/mol Other known titles Fragment 176-191: AOD 9604, GH (hGH) lipolytic fragment, Somatostatin (177-191), tyrosyl CJC-1295: Mod GRF 1-29, CJC-1295 without DAC Ipamorelin Ipamorelin Acetate, IPA Research and Clinical Studies Fragment 176-191 & CJC-1295 & Ipamorelin Blend, and Growth Hormones While the fragment 176-191 appears to directly mimic the function of hGH, the peptides CJC-1295 and Ipamorelin appear to exert potential by upregulating the synthesis of hGH itself. For example, CJC-1295 has been suggested to have significant hGH-boosting potential in several phase-1 clinical trials. In the first, test subjects aged between 20 and 40 were enrolled.(4) All subjects were divided into two groups – one was presented with a saline placebo and the rest with the CJC-1295 peptide. A blood sample was collected from all subjects before and after the peptide presentation. After completion of the study, it was reported by the researchers that the peptide group appeared to exhibit a 7.5-fold increase in their growth hormone levels compared to the standard group. The trend suggested that these hormones increased gradually throughout the study and remained unchanged for at least 7 days after discontinuing presentation. Another study(5) was conducted on male test subjects aged between 20 and 60. Similar to the previous study, these subjects were divided into two groups – one was presented with a placebo while the rest were given the CJC-1295 peptide. The peptide group was given gradually increasing concentrations of the compound during the study. Upon analyzing the blood samples collected from these subjects, it was observed that there appeared to be a concentration-dependent increase, of up to 10 times, in the concentration of growth hormones among the peptide subjects. As per Madalina Ionescu et al., “The marked enhancement of trough GH levels by continuous GHRH stimulation implicates the importance of this effect on increasing IGF-I. Long-acting GHRH preparations may benefit patients with intact pituitary GH secretory capability.” (4) Similarly, Ipamorelin has also been suggested to potentially increase hGH synthesis. In one clinical study it was posited that a single presentation of the peptide may boost hGH levels by over 60-fold compared to placebo.(6) Fragment 176-191 & CJC-1295 & Ipamorelin Blend, and Lipolytic Action A clinical trial(7) was conducted in 2004 to study the peptide’s potential lipolytic (fat-burning) action. In the trial, 300 subjects were enrolled and presented with the Fragment 176-191 peptide for 12 weeks. These subjects were divided into 6 groups – one given a saline placebo, and the rest presented with different peptide concentrations. The group presented with minimal peptide presence appeared to exhibit a notable reduction in their body weight (up to 2.8 kilograms). These peptides may have also helped improve these subjects’ cholesterol profiles and glucose tolerance levels. The research team stated, “The evidence from the trial is that over 12 weeks, [the peptide] induces competitive weight loss with accompanying health benefits…” Fragment 176-191 & CJC-1295 & Ipamorelin Blend, and Regeneration Thirty-two experimental rabbits were examined as part of this 2015 study,(8) all of whom were 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 for about 7 weeks. After the completion of the study, all rabbits were checked for any signs of cartilage damage. Among all groups, the rabbits presented with peptide and hyaluronic acid combination appeared to show minimal cartilage degeneration. These results suggest that the peptide may have the capability to enhance cartilage regeneration and repair. The report concluded that “Intra-articular AOD9604 using ultrasound guidance enhanced cartilage regeneration, and combined AOD9604 and HA were more effective than HA or AOD9604 alone in the collagenase-induced knee OA rabbit model.” (8) Fragment 176-191 & CJC-1295 & Ipamorelin Blend, and Body Composition As mentioned, Fragment 176-191 may potentiate a favorable shift in body composition by reducing adiposity. Yet, CJC-1295 & Ipamorelin also appear to have a significant potential via different impacts, which may include increasing lean mass for CJC-1295, and increasing overall body weight in the case of Ipamorelin. Research in the lab suggests that Ipamorelin might potentially play a role in weight gain including muscle mass gain but also adiposity, possibly due to both an elevation in hGH levels and its potential to stimulate appetite through ghrelin receptor activation. An investigation into Ipamorelin's potential impact on body fat was conducted in both hGH-deficient and hGH-intact murine models. The results indicated that Ipamorelin may have led to a modest 15% rise in body weight within a span of 2 weeks. Additionally, in both murine models, there was a relative increase in fat pad weights when compared to overall body weight.(9) On the other hand, CJC-1295 may potentially improve body composition while apparently increasing muscle mass without affecting or even possibly decreasing adiposity. Research involving murine models with a GHRH gene deletion (known as GHRHKO) noted that CJC-1295 might upregulate the synthesis of GH and potentially induce such a favorable shift in body composition. When these GHRHKO murine models were exposed to CJC-1295, they seemed to maintain standard lean mass, compared to unexposed models which failed to achieve normal lean mass. Moreover, the subcutaneous fat mass remained at control levels across all peptide-associated groups, while the GHRHKO murine models not exposed to CJC-1295 appeared to have increased adiposity.(10) Considering the potential lipolytic action of Fragment 176-191 and CJC-1295, researchers may want to consider the hypothesis that the blend of these peptides may counteract the fat-increasing potential of Ipamorelin, while further increasing its muscle building potential. Fragment 176-191 & CJC-1295 & Ipamorelin Blend, and Bone Mineral Content By increasing lean and muscle mass, the peptides and especially Ipamorelin may provide potential benefits in bone mass. In an experiment, murine subjects were either introduced to Ipamorelin or a control substance. The impact of Ipamorelin on bone mineral content was observed in real-time using dual X-ray absorptiometry (DXA) at select areas, notably the femur and L6 vertebrae. Following the study period, the femurs of the murine subjects were examined using mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. Preliminary results suggest that the peptide might have played a role in a possible weight increase and a potential rise in the tibial and vertebral bone mineral content as detected by DXA, compared to the control group. The pQCT findings hint that the increase in cortical BMC might be due to an expansion in the cross-sectional bone area.(11) Fragment 176-191 & CJC-1295 & 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 National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 9831659, Ipamorelin. https://pubchem.ncbi.nlm.nih.gov/compound/Ipamorelin 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 Ionescu M, Frohman LA. Pulsatile growth hormone secretion (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006 Dec;91(12):4792-7. doi: 10.1210/jc.2006-1702. Epub 2006 Oct 3. PMID: 17018654. https://pubmed.ncbi.nlm.nih.gov/17018654/ Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006 Mar;91(3):799-805. doi: 10.1210/jc.2005-1536. Epub 2005 Dec 13. PMID: 16352683. https://pubmed.ncbi.nlm.nih.gov/16352683/ 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 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/ 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 Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1290-4. doi: 10.1152/ajpendo.00201.2006. Epub 2006 Jul 5. PMID: 16822960. 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.
Receptor Grade IGF-1 LR3 (100mcg)
Insulin-like Growth factor-1, or IGF-1, is a naturally produced protein with 70 amino acids. Receptor Grade IGF-1 LR3 is a synthetic variant of the naturally occurring IGF-1, which contains an extended N-terminal structure of 13 amino acids and a replacement of the glutamic acid at residue 3 with arginine. Hence, it is named IGF-1 Long R3.(1)(2) Owing to the altered structure, Receptor Grade IGF-1 LR3 has been suggested to have increased affinity and increased anabolic potential while also binding less to IGF-1 binding proteins (IGF-1BPs). Structurally similar to insulin, this IGF-1 LR3 has the potential primarily to regulate cell tissue growth and development. This potential has been evaluated in cell growth studies, throughout which researchers first prompted the need for developing this high-potency variant. Moreover, the classification of Receptor Grade refers to the purity of the material, which is considered higher than Media Grade IGF-1 LR3. Chemical Makeup(2,3) Molecular Formula: C400H625N111O115S9 Molecular Weight: 9117.5 g/mol Other Known Titles: Long-(arg3) insulin-like growth factor-I, Insulin-like growth factor long chain R3 Research and Clinical Studies Receptor Grade IGF-1 LR3 and Anabolic Potential Unfortunately, research on the anabolic potential of IGF-1 LR3 is lacking, as the peptide is aimed towards cell culture studies. Yet, of the few experiments in murine models, researchers have suggested the significant potential of the peptide.(1) In one study, experiments were carried out on normal and dexamethasone-induced catabolic murine models. It was noted that IGF-1 LR3 might potentially be 1.5 to 2 times as anabolic as IGF-I in inducing weight gain, increasing visceral organ weights, and possibly enhancing feed use efficiency under continuous delivery conditions. Moreover, IGF-1 LR3 appeared to have retained the potential for greater potency than IGF-I in several metrics, even in studies of only intermittent exposure. Additionally, in murine models exposed to dexamethasone, it was observed that the excretion of Nτ-methylhistidine—a marker indicative of muscle protein breakdown—appeared reduced to a greater extent by IGF-1 LR3, potentially threefold more than by IGF-I. This suggests that IGF-1 LR3 may host the potential, though not consistently equivalent across all parameters, to exhibit enhanced anabolic actions under certain laboratory conditions. Therefore, Receptor Grade IGF-1 LR3 may be posited to exert even greater anabolic potential than IGF-1. To provide a comparison, several studies have researched the anabolic potential of IGF-1. For example, a study(4) was conducted in 2005 to study the potential of the peptide in models of IGF-1 deficiency. Following peptide exposure, the length and growth of the models were assessed and analyzed against control thresholds. Based on the study findings, it was observed that total length increased in all peptide-exposed models by a significant margin against the control standards. This study suggests that IGF-1, and possibly also more potent analogs like Receptor Grade IGF-1 LR3 peptide, may have some potential in mitigating growth deficiency. Receptor Grade IGF-1 LR3 and Insulin Receptor Sensitivity Research(5) has suggested that IGF proteins typically bind to IGF-1 receptors and may stimulate glucose uptake, potentially through a signaling mechanism involving PI3K and AMPK pathways. However, when studied, peptides like Receptor Grade IGF-1 LR3 appeared to induce glucose uptake not just through IGF-1 receptor interactions but also independently, possibly via other pathways or receptors. This suggests that the mechanism of glucose uptake might involve additional cellular processes beyond the traditional receptor binding. Assefa B Mahmoud et al. stated, "Multiple [...] studies reported the role of IGF-1 in enhancing insulin sensitivity and glucose metabolism. A low-serum level of IGF-1 has been associated with insulin resistance, and [...] recombinant IGF-1 has been [hypothesized] to improve insulin sensitivity and glucose metabolism.” Receptor Grade IGF-1 LR3 and Cell Lifespan Research(6) on murine models observed that common markers of physiological decline, such as muscle tears and neurological deficiencies, appeared to be mitigated for an extended period following routine exposure to the peptide. While more detailed studies and clinical trials are pending, the above preliminary study suggests that the peptide may indirectly help to increase lifespan of functional cells. As per William E. Sonntag et al., “Based on this review, we conclude that the perceived contradictory roles of growth hormone and insulin-like growth factor-1 in the genesis of the aging phenotype should not be interpreted as a controversy on whether growth hormone or insulin-like growth factor-1 increases or decreases life span but rather as an opportunity to explore the complex roles of these hormones during specific stages of the life span.” Receptor Grade IGF-1 LR3 and Muscle Cells A study(7) was conducted on female murine models to identify the IGF-1 LR3 peptide’s potential in decreasing the action of myostatin. Myostatin is considered to prevent cellular differentiation; mitigating the actions of this protein may increase lean muscle and reduce fat cell storage and fatty mass. The study's results suggested that the various IGF-1 analogs, including Receptor Grade IGF-1 LR3, appear to potentially reverse adverse myostatin and prevent apoptosis. Receptor Grade IGF-1 LR3 and Shorter Action An experimental mouse model was created for a study(8) where the IGF-1 LR3 peptide was compared to the endogenous IGF-1. Throughout the study, it was observed that when the peptide was exposed to the murine model, it appeared to quickly clear from the serum and evenly distribute into tissue. More specifically, the researchers posited that IGF-1 LR3 cleared faster as it appeared to bind to a lower degree to binding proteins than endogenous IGF-1. This reduced binding affinity means IGF-1 LR3 might circulate more freely than IGF-I. The analysis of tissue distribution patterns of IGF-1 LR3 also suggested a potentially unique localization compared to IGF-I. Elevated levels of the IGF-1 LR3 tracer were observed in tissues such as kidneys, ovaries, and adrenal glands in murine models. This distinct distribution suggests that the organs primarily involved in metabolic and reproductive functions may exhibit varying capacities for the uptake or retention of IGF-1 LR3 in contrast to IGF-I. It is hypothesized that these differences might stem from IGF-1 LR3's diminished propensity to form complexes with IGFBPs, which might influence its bioavailability and interaction with target tissues in experimental models. Nevertheless, further research suggested that a peptide with similar modifications (namely R3) to IGF-1 LR3 may exert increased anabolic potential compared to regular IGF-1 despite the shorter action.(9) Receptor Grade IGF-1 LR3 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References Tomas, F. M., Knowles, S. E., Owens, P. C., Chandler, C. S., Francis, G. L., Read, L. C., & Ballard, F. J. (1992). Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats. The Biochemical journal, 282 ( Pt 1)(Pt 1), 91–97. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1130894/ Human Insulin-like growth factor. Protein Data Bank in Europe, https://www.ebi.ac.uk/pdbe/entry/pdb/1gzr National Center for Biotechnology Information (2023). PubChem Substance Record for SID 381123731, M9L22Y19H9, Source: ChemIDplus. Retrieved January 24, 2023 from https://pubchem.ncbi.nlm.nih.gov/substance/381123731. Anderson, L. J., Tamayose, J. M., & Garcia, J. M. (2018). Use of growth hormone, IGF-I, and insulin for anabolic purpose: Pharmacological basis, methods of detection, and adverse effects. Molecular and cellular endocrinology, 464, 65–74. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723243/ Assefa, B., Mahmoud, A. M., Pfeiffer, A., Birkenfeld, A. L., Spranger, J., & Arafat, A. M. (2017). Insulin-Like Growth Factor (IGF) Binding Protein-2, Independently of IGF-1, Induces GLUT-4 Translocation and Glucose Uptake in 3T3-L1 Adipocytes. Oxidative medicine and cellular longevity, 2017 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750484/ William E. Sonntag, Anna Csiszar, Raphael de Cabo, Luigi Ferrucci, Zoltan Ungvari, Diverse Roles of Growth Hormone and Insulin-Like Growth Factor-1 in Mammalian Aging: Progress and Controversies, The Journals of Gerontology: Series A, Volume 67A, Issue 6, June 2012, Pages 587–598, https://doi.org/10.1093/gerona/gls115 Naisi Li, Qiyuan Yang, Ryan G. Walker, Thomas B. Thompson, Min Du, Buel D. Rodgers, Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis, Endocrinology, Volume 157, Issue 1, 1 January 2016, Pages 282–291. https://doi.org/10.1210/en.2015-1546 Bastian SE, Walton PE, Wallace JC, Ballard FJ. Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I) and an analogue LR3IGF-I in pregnant rats. J Endocrinol. 1993 Aug;138(2):327-36. doi: 10.1677/joe.0.1380327. PMID: 7693845. Elis S, Wu Y, Courtland HW, Cannata D, Sun H, Beth-On M, Liu C, Jasper H, Domené H, Karabatas L, Guida C, Basta-Pljakic J, Cardoso L, Rosen CJ, Frystyk J, Yakar S. Unbound (bioavailable) IGF1 enhances somatic growth. Dis Model Mech. 2011 Sep;4(5):649-58. doi: 10.1242/dmm.006775. Epub 2011 May 31. PMID: 21628395; PMCID: PMC3180229. 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.
Cortagen (20mg)
Cortagen is posited to be a synthetic tetrapeptide with the sequence Ala–Glu–Asp–Pro, originally designed based on amino acid analysis of the polypeptide complex cortexin. It is classified among the so-called Khavinson peptides – a family of short peptide bioregulators that are proposed to modulate endogenous regulatory systems rather than acting as classical receptor agonists or enzyme inhibitors.(1) These are low-molecular-weight peptides that are posited to be able to penetrate cells and reach the nucleus, where they may interact directly with DNA and chromatin structures in mammalian research models. In vitro studies suggest that AACC may be a preferred DNA-binding sequence for Cortagen, raising the hypothesis that it may selectively support transcription at gene sites containing this motif and thereby exert epigenetic-like actions on gene expression. Currently, it appears to be under investigation in laboratory settings for its potential to support stress signaling in different cell cultures, including nerve cell circuits. Chemical Makeup Other Known Titles: AEDP, Ala-Glu-Asp-Pro Molecular Weight: 430.4 g/mol Molecular Formula: C17H26N4O9 Research and Clinical Studies Epigenetic Potential of Cortagen Research by Lezhava et al. suggests that Cortagen may have epigenetic support for aged cells, potentially restoring the expression of genes suppressed by the aging process of the cell via condensation of the chromatin.(2) According to the researchers, Cortagen was applied to lymphoid cell cultures exhibiting an aged chromatin profile to assess its potential. Differential scanning calorimetry suggested that chromatin was thermodynamically less stable and therefore more uncondensed following Cortagen experimentation. These study authors proposed that Cortagen may partially unfold higher-order chromatin structures, such as loops of 30-nm fibers and even 10-nm nucleosomal filaments into more relaxed 5-nm fibers, implying that the “Peptidebioregulator Cortagen induces unrolling deheterochromatinization (decondensation) of total heterochromatin” in both structural and facultative chromatin domains. Consequently, ribosomal gene clusters may become more transcriptionally active, potentially supporting protein synthesis capacity in these aged cells. Yet, Cortagen does not appear to remodel all constitutive blocks as pericentromeric C-heterochromatin on chromosomes analogous to 1, 9, and 16 remained structurally stable. Cortagen also appeared to increase sister chromatid exchange (SCE) frequency in some chromosome groups, which the authors viewed as a potential cytogenetic marker of facultative heterochromatin decondensation and possible re-release of previously repressed genes. Cortagen Research into Oxidative Stress According to the research of Kozina et al., Cortagne may support lipid peroxidation and oxidative modification of proteins in mammalian research models.(3) According to the team of scientists, Cortagen exposure was associated with “decreased the content of LPO products and reduced oxidative modification of proteins” in both neural cells and the surrounding protein-rich medium. In the cells, the peptide also tended to lower later-stage products. In parallel, Cortagen appeared to reduce the accumulation of protein carbonyl groups, which act as markers of oxidative protein modification, and appeared to achieve a significant reduction in neural cells, and by about 15% in the extracellular fraction. These authors suggested that Cortagen may interfere with the chain of reactions whereby reactive lipid species attack amino groups in proteins, possibly limiting downstream carbonyl formation. Yet, Cortagen’s potential was apparent only in integrated biological models, suggesting that it may not act as a simple radical scavenger, but instead possibly modulates the generation of reactive species upstream, or alters how cells handle oxidative stress. Thus, the researchers suggest that Cortagen may exert an indirect antioxidant-like action in neural systems by dampening lipid and protein oxidation. Cortagen Research into Cellular Stress Response and Differentiation Studies involving a transcriptome-wide analysis of Cortagen’s potential on cardiac muscle cell genes suggest that the peptide may support the cellular stress response of such cultures. Specifically, Anisimov et al. suggested that Cortagen may modulate genes related to carrier proteins and membrane transport, as well as DNA synthesis and replication involved in that response.(4) This pattern of changes is interpreted as potentially supporting intracellular transport processes and proliferative or reparative programs at the transcriptional level. Cortagen also apparently up-regulated several mitochondrial genes (16S rRNA, COX3, ND5), which may theoretically interact with bioenergetics. In parallel, transcripts linked to ionic homeostasis and Ca²⁺ handling were altered, hinting at a possible support for excitation–contraction coupling pathways. Among particularly notable targets, Cortagen increased expression of stress-response genes (Pass1, Hsc70), developmental and survival-related signals (Bmp2, Wnt4), and components of mitogenic or survival signaling (Eps15, Eps15-rs). The authors posit that these coordinated transcriptional shifts may underlie some of Cortagen’s broader biological actions and suggest that the peptide may serve as a helpful laboratory tool for exploring peptide-mediated regulation of stress-response networks in vitro. Further research by Khavinson et al. suggested that by modifying gene expression, the peptide may also support cellular differentiation.(5) Experimentally, the authors examined Cortagen in an in vitro model using pluripotent embryonic ectodermal tissue. Ectodermal explants were incubated for 1 hour in solutions of Cortagen and then cultured. In the reference medium without peptides, the pluripotent ectoderm apparently gave rise only to atypical epidermis. By contrast, exposure to Cortagen induced the same pluripotent cells to differentiate into epidermal and mesenchymal cells, suggesting that these peptides may broaden the available differentiation pathways. Cortagen Research into Neurological Stress Signaling and Nerve Regeneration Cortagen has been examined in laboratory studies by Adriani et al., who have been investigating the activation of arousal- and stress-linked circuits through global output patterns. The scientists observed that the peptide apparently may support output from neural networks associated with arousal and exploratory drive, without concurrently amplifying stress-linked appraisal signals. This pattern may reflect a state in which outward-oriented processing dominates over internal “risk-checking” loops, suggesting a shift in the balance of stress-signaling within the network. The potential implications of Cortagen on nerve regeneration may better support these observations. GA group of researchers, led by Turchaninova et. al., investigated the neuroregenerative potential of Cortagen. The scientists transected sciatic nerve trunks, which were then micro-sutured and studied in vitro on a multielectrode platform. Compound action potentials (CAPs) were recorded at defined distances distal to the suture line. Cortagen apparently increased the length of the nerve segment able to conduct impulses by 27% and better-supported conduction velocity by 40% compared to placebo. The authors also suggested that the peptide may preferentially support regeneration where baseline growth is lower, rather than extending growth beyond the usual maximal range. This faster conduction is interpreted as a potential marker of more advanced functional maturation, possibly involving better-supported myelination and fiber calibre. Cortagen peptide is available for research and laboratory purposes only. Please review our Terms and Conditions before ordering. References: Khavinson, V. Kh, N. S. Lin’kova, and S. I. Tarnovskaya. "Short peptides regulate gene expression." Bulletin of experimental biology and medicine 162.2 (2016): 288-292. Lezhava, Teimuraz, et al. "Epigenetic Regulation of “Aged” Heterochromatin by Peptide Bioregulator Cortagen." International Journal of Peptide Research and Therapeutics 21.1 (2015): 157-163. Kozina, L. S. "Effects of bioactive tetrapeptides on free-radical processes." Bulletin of experimental biology and medicine 143.6 (2007): 744-746. Anisimov SV, Khavinson VKh, Anisimov VN. Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray. Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):87-93. PMID: 15159690. Khavinson V, Linkova N, Diatlova A, Trofimova S. Peptide Regulation of Cell Differentiation. Stem Cell Rev Rep. 2020 Feb;16(1):118-125. doi: 10.1007/s12015-019-09938-8. PMID: 31808038. Adriani, Walter, et al. "Modulatory effects of cortexin and cortagen on locomotor activity and anxiety-related behavior in mice." The Open Neuropsychopharmacology Journal 2.1 (2009): 22-29. Turchaninova LN, Kolosova LI, Malinin VV, Moiseeva AB, Nozdrachev AD, Khavinson VK. Effect of tetrapeptide cortagen on regeneration of sciatic nerve. Bull Exp Biol Med. 2000 Dec;130(12):1172-4. PMID: 11276314. 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.
Epithalon (25mg)
Research has suggested that Epithalon, (also known as AEDG peptide, tetrapeptide Epitalon, Epithalon, or Epithalone) may regulate the function of the brain, the pineal gland, and the eye retina. Studies in the peptide have spurred numerous research hypotheses, which include possible sleep regulation via pineal gland stimulation, releasing more melatonin. Studies also speculate that the peptide may stimulate the generation of telomerase, may exhibit strong antioxidant characteristics, and extend the retina's workable integrity. With recent technology and ongoing advances in the scientific field, methods have been developed to synthesize complex peptide preparations from the extracts of several different tissues. One such peptide in the tissues is ‘Epithalamin,’ naturally produced in the pineal gland. Epithalamin has been suggested to be functional in increasing melatonin production, improving the immunological and anti-carcinogenic functions in rats and mice, and restoring reproductive function in aged rodents. Utilizing the recent advancements in science, a peptide similar to Epithalamin was synthesized and titled ‘Epithalon.’ Epithalon is derived from a naturally occurring peptide belonging to both the pineal gland and eye retina.(1) Overview Epithalon is a synthetic tetrapeptide, also known as AEDG peptide, composed of amino acids Ala-Glu-Asp-Gly.(2) The peptide has been suggested to exhibit action similar to Epithalamin via various modes. Epithalamin is a related pineal peptide preparation containing Epithalon, that has been purported to potentially increase the average lifespan of various experimental models by 11–31% and may reduce mortality in murine models by a suggested 52%.(3) This potential mechanism and further studies are described below. Chemical Makeup Molecular Formula: C14H22N4O9 Molecular Weight: 390.34 g/mol Other Known Titles: Epitalon, Epithalone Research and Clinical Studies Epithalon Peptide and Longevity A study investigated the potential mechanisms of Epithalon in influencing gene expression and protein synthesis in stem cells such as gingival mesenchymal stem cells (hGMSCs). The study(2) has suggested that the peptide binds with the histones - HI/6 and HI/3 – located at different sites in tissue, which then interact with the DNA. More specifically, the study posits that Epithalon may alter chromatin structure by specifically interacting with histones, thereby modulating gene expression. This interaction might involve the peptide acting as a histone mimic, facilitating changes in chromatin dynamics. Epithalon's epigenetic regulation might involve competitive binding with histones at DNA interaction sites, increasing transcription of genes involved in neuronal differentiation. Such binding may displace other regulatory proteins, making DNA more accessible for transcriptional machinery, potentially inducing neuronal cell differentiation in retinal and periodontal ligament stem cells (hPDLSCs). This experimentation led to an upregulation of neurogenic differentiation markers, including Nestin, GAP43, β Tubulin III, and Doublecortin, in hGMSCs. Specifically, mRNA expression of these markers increased by 1.6 to 1.8 times. Considering the changes in these markers, the potential upregulation of neuronal differentiation and protein synthesis in retinal and ligament stem cells may lead to enhanced functionality. Epithalon Peptide and Oxidative Stress A recent study suggested that Epithalon might reduce intracellular reactive oxygen species (ROS) levels in aged oocyte cells, potentially exhibiting antioxidative actions.(4) The peptide was suggested to significantly lower ROS levels, unlike higher concentrations that did not demonstrate similar protective actions. Such a reduction might be critical, as oxidative stress is considered a significant factor in cellular aging. Additionally, Epithalon may help preserve the structural integrity of oocytes. It was observed to possibly decrease fragmentation in post-ovulatory aged oocytes and during parthenogenetic activation—a process where an egg develops into an embryo without fertilization. The peptide also potentially maintains spindle integrity and correct distribution of cortical granules (CG). Spindles, which are crucial structures in cell division that distribute chromosomes to daughter cells, and cortical granules, secretory vesicles important for preventing polyspermy (the fertilization of an egg by multiple sperm), are essential for normal cell division and fertilization. Epithalon might correct spindle abnormalities and prevent the misplacement of CGs, which are common issues in aged oocytes. Moreover, Epithalon exposure was associated with potential improvements in mitochondrial function, which is vital for oocyte viability. Mitochondria, known as the cell's powerhouses, are deemed crucial for ATP production and maintaining cellular metabolism. There were indications of enhanced mitochondrial membrane potential and increased mtDNA copy numbers, suggesting that Epithalon might support mitochondrial integrity and functionality as oocytes age. Finally, the peptide was suggested to reduce DNA damage and apoptosis (cell death) in aged oocytes. It appeared to lower the intensity of γH2AX signals—a marker of DNA damage—and seemed to decrease apoptosis rates, as indicated by reduced Annexin-V staining. These observations imply that Epithalon might enhance oocyte survival by potentially mitigating oxidative damage and preserving genomic stability, which are considered crucial for maintaining the overall functionality of the cells. Epithalon Peptide and Anti-Aging In order to understand the anti-aging action of various synthetic peptides, studies have been widely conducted to study their potential in cell proliferation, cell regeneration and aging, cellular apoptosis, and matrix modeling.(5) It was suggested that Epithalon may inhibit the synthesis of MM-9, which usually increases with time, and increase the proliferation and cellular regeneration process, which usually decreases with time. More specifically, the researchers posited that the peptide may have “enhanced the expression of Ki-67 and CD98hc that are less intensively synthesized during cell aging.” Epithalon also seemed to inhibit the activity of Caspase-3, a crucial enzyme believed to facilitate apoptosis (programmed cell death). The researchers commented that the peptide “suppressed caspase-dependent apoptosis that increases during aging of cell cultures.” By potentially restraining Caspase-3 activity, Epithalon might support cellular longevity and decrease apoptosis, enhancing its regenerative capabilities. Epithalon Peptide and Fetal Studies This study(6) was conducted to understand the proliferative potential of the peptide on fetal fibroblastic cells. Pulmonary fibroblasts were isolated from the 24-week-old fetus, and it was observed that these fibroblasts appeared to lose their proliferative function at the 34th passage. These cells possessed extremely small telomeres sizes – smaller than what they originally were during the 10th passage. When Epithalon was presented in these otherwise aging cells, it appeared to stimulate the development of telomeres, causing them to increase and restore their normal size. As a result of this size elongation, the telomeres appeared to cause 10 extra cell divisions than usual seen in the control cells. Thus, this study suggested that Epithalon overcame the Hayflick limit and extended the normal cell cycle in the cells.(6) Epithalon Peptide and Lymphocytic Cells In this clinical study,(7) lymphocytic cells were isolated and cultured from subjects aged between 76 and 80 years. The purpose of this study was to determine the action of Epithalon on ribosomal cell activity and its impact on denaturation and polymorphism of heterochromatin. The outcome of this study, following the delivery of the cell culture with Epithalon, was that the peptide appeared to induce activation of the ribosomal genes and decondensation of the heterochromatin. Consequently, it appeared to induce the release of genes that were otherwise suppressed due to the aging of the chromosomal regions. This study suggested that Epithalon might have the potential to modify the chromosome regions in the aging cells, activate chromatin, and restore cellular activities that were otherwise suppressed or delayed in geriatric subjects. Epithalon Peptide and Anti-Mutagenic Action In this 2011 study,(8) three different mice models were used to determine the action of the peptide on chromosomal aberrations. The three mice models were – SAMP-1 female mice with accelerated aging and wild rats SAMR-1 and SHR (both female mice). Upon delivery of Epithalon, it was observed that the incidence of the chromosomal aberrations in the bone marrow of SAMP-1 mice with accelerated aging appeared to be almost 2 times higher than the other two models. When the peptide was presented at 2 months in the mice, it appeared to decrease the chromosomal aberrations in all three models, the highest being in the SAMP-1 mice with accelerated cell aging. In combination with melatonin at night, given with water, there was no reported impact on the action of the peptide. This study suggested that Epithalon may possess anti-mutagenic potential. Epithalon Peptide and Cancer Cells In this study,(9) one-year-old female (C3H/He) mice with tumors on the reproductive organs (mammary glands and ovaries) were observed. The tumors on the mammary glands included several variants of the invasive ductal carcinogenic cells, whereas, in the ovaries, the tumors found were granulosa cell tumors. These mice, kept in standard conditions for six months, were divided into control and experimental groups. Epithalon was presented five times a week. Once the study was completed, it was reported that three out of the nine mice in the control group appeared to exhibit metastasis and increased tumor cells. Meanwhile, the peptide mice exhibited a decrease in the number of tumor cells. Epithalon, upon delivery, appeared to inhibit the process of metastasis in the mice, preventing tumor cell cycle and growth. Researchers of this study posited the anti-metastatic potential of the peptide. Epithalon Peptide and Research in Hypophysectomized Birds In this study,(10) hypophysectomized birds, both young and old, were used to study the action of Epithalon peptide on the morphology of the thymus gland. Hypophysectomized birds are birds in which the pituitary gland has been surgically removed. Upon delivery of the peptide, it was discovered that the morphology of the thymus gland appeared to be restored in all birds, regardless of their age. The most improved results were observed on birds (mainly chickens) that underwent neonatal hypophysectomy before the peptide was presented. Epithalon Peptide and Melatonin Levels This study(11) was carried out on aging monkeys to determine the actions of Epithalon on melatonin levels. With increasing age, the melatonin levels tend to decrease due to reduced secretion, which may cause difficulty in sleep regulation. This is mainly due to the functioning of the pineal gland deteriorating with increased age and a reduction of hormone circadian rhythm amplitude. Upon delivery of Epithalon, it appeared to stimulate actions similar to those caused by the natural secretion of the pineal gland. The melatonin levels appeared to increase to "normal" levels. Epithalon Peptide and Retinal Cells In this clinical study,(12) it was suggested that when Epithalon was presented in geriatric subjects, it appeared to elevate the bioelectric and functional activities in the retina, thereby preserving the morphological structure of the retina. More specifically, the researchers posited that the peptide “participates in the mechanisms of transcription common for the epiphysis and retina.”As a result, age-related retinal degeneration may be reversed in the older subjects, which is supported by the positive clinical outcome in 90% of the subjects presented with the peptide. Epithalon and Geroprotective Properties This study(13) was conducted on 266 elderly subjects (over the age of 60 years) throughout 6 to 8 years, where some subjects were presented with peptide-bioregulator Thymalin, others with Epithalon, and the rest with the combination of the two. After the study, it was observed that both the peptides appeared to have the potential to restore basic bodily functions in geriatric subjects – including improved functions in the cardiovascular, endocrinal, immune, and nervous systems, along with normalized metabolic and hemostatic activities. The peptide groups appeared to exhibit a 2-fold decrease in the common geriatric disorders such as acute respiratory disorder, heart diseases, and bone disorders. Additionally, the mortality rate in the peptide subjects appeared to significantly decrease, with a 2-fold decrease in the Thymalin subjects, a 1.8-fold decrease in the Epithalon subjects, and 2.5-fold decrease in the subjects presented with both peptides. Epithalon peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Khavinson VKh. Peptides and Ageing. Neuro Endocrinol Lett. 2002;23 Suppl 3:11-144. PMID: 12374906. https://pubmed.ncbi.nlm.nih.gov/12374906/ Khavinson, Vladimir et al. “AEDG Peptide (Epithalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism.” Molecules (Basel, Switzerland) vol. 25,3 609. 30 Jan. 2020, doi:10.3390/molecules25030609. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037223/ Anisimov VN, Mylnikov SV, Khavinson VK. Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats. Mech Ageing Dev. 1998 Jun 15;103(2):123-32. doi: 10.1016/s0047-6374(98)00034-7. PMID: 9701766. Yue X, Liu SL, Guo JN, Meng TG, Zhang XR, Li HX, Song CY, Wang ZB, Schatten H, Sun QY, Guo XP. Epithalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro. Aging (Albany NY). 2022 Apr 12;14(7):3191-3202. doi: 10.18632/aging.204007. Epub 2022 Apr 12. PMID: 35413689; PMCID: PMC9037278. Lin’kova, N.S., Drobintseva, A.O., Orlova, O.A. et al. Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro . Bull Exp Biol Med 161, 175–178 (2016). Khavinson VKh, Bondarev IE, Butyugov AA, Smirnova TD. Peptide promotes overcoming of the division limit in human somatic cell. Bull Exp Biol Med. 2004 May;137(5):503-6. doi: 10.1023/b:bebm.0000038164.49947.8c. PMID: 15455129. https://pubmed.ncbi.nlm.nih.gov/15455129/ Khavinson VKh, Lezhava TA, Monaselidze JR, Jokhadze TA, Dvalishvili NA, Bablishvili NK, Trofimova SV. Peptide Epithalon activates chromatin at the old age. Neuro Endocrinol Lett. 2003 Oct;24(5):329-33. PMID: 14647006. https://pubmed.ncbi.nlm.nih.gov/14647006/ Rosenfeld SV, Togo EF, Mikheev VS, Popovich IG, Khavinson VKh, Anisimov VN. Effect of Epithalon on the incidence of chromosome aberrations in senescence-accelerated mice. Bull Exp Biol Med. 2002 Mar;133(3):274-6. doi: 10.1023/a:1015899003974. PMID: 12360351. https://pubmed.ncbi.nlm.nih.gov/12360351/ Kossoy G, Anisimov VN, Ben-Hur H, Kossoy N, Zusman I. Effect of the synthetic pineal peptide Epithalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo. 2006 Mar-Apr;20(2):253-7. PMID: 16634527. https://pubmed.ncbi.nlm.nih.gov/16634527/ Pateyk AV, Baranchugova LM, Rusaeva NS, Obydenko VI, Kuznik BI. Effect of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the morphology of the thymus in hypophysectomized young and old birds. Bull Exp Biol Med. 2013 Mar;154(5):681-5. doi: 10.1007/s10517-013-2029-0. PMID: 23658898. https://pubmed.ncbi.nlm.nih.gov/23658898/ Korkushko OV, Lapin BA, Goncharova ND, Khavinson VKh, Shatilo VB, Vengerin AA, Antoniuk-Shcheglova IA, Magdich LV. [Normalizing effect of the pineal gland peptides on the daily melatonin rhythm in old monkeys and elderly people]. Adv Gerontol. 2007;20(1):74-85. Russian Khavinson V, Razumovsky M, Trofimova S, Grigorian R, Razumovskaya A. Pineal-regulating tetrapeptide Epithalon improves eye retina condition in retinitis pigmentosa. Neuro Endocrinol Lett. 2002 Aug;23(4):365-8. PMID: 12195242. https://pubmed.ncbi.nlm.nih.gov/12195242/ Khavinson VKh, Morozov VG. Geroprotektornaia éffektivnost' timalina i épitalamina [Geroprotective effect of thymalin and Epithalamin]. Adv Gerontol. 2002;10:74-84. Russian. PMID: 12577695. https://pubmed.ncbi.nlm.nih.gov/12577695/ Korkushko OV, Khavinson VKh, Shatilo VB, Antonyuk-Shcheglova IA. Geroprotective effect of Epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging. Bull Exp Biol Med. 2006 Sep;142(3):356-9. English, Russian. doi: 10.1007/s10517-006-0365-z. PMID: 17426848. https://pubmed.ncbi.nlm.nih.gov/17426848/ 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.
KLOW (BPC-157, KPV, TB-500, GHK-Cu) Blend (80mg)
BPC-157, TB-500, GHK-Cu, and KPV (KLOW blend) are peptides under investigation in laboratory models for their potential to support inflammatory signaling, angiogenesis, and repair mechanisms. Structurally, they differ considerably. BPC-157 appears to be a synthetic pentadecapeptide, TB-500 mirrors the endogenous thymosin beta-4, GHK-Cu is a tripeptide with a copper ion, and KPV represents the C-terminal segment of alpha-melanocyte-stimulating hormone. Each peptide appears to converge on overlapping repair-associated processes, which supports the hypothesis that their combined exposure is the KLOW Blend. Together, these four peptides form what is referred to as the KLOW Blend, because their actions are hypothesized to be partly overlapping and partly complementary based on the available research data. Chemical Makeup Other Known Titles BPC-157: C62H98N16O22 KPV: C16H30N4O4 TB-500: C212H350N56O78S GHK-Cu: C14H23CuN6O4 Molecular Weight: BPC-157:5 g/mol KPV: 43 g/mol TB-500: 4963 g/mol GHK-Cu: 38 g/mol Molecular Formula: BPC-157: Body Protection Compound-157 KPV: MSH(11-13), ACTH(11-13), alpha-MSH(11-13) TB-500: Synthetic Thymosin Beta-4 GHK-Cu: glycyl-L-histidyl-L-lysine-copper 2+ Research and Clinical Studies KLOW Blend Peptides and Potential Properties BPC-157 appears to be a synthetic peptide built from fifteen amino acids, with a potential parent protein remaining undefined. Laboratory models by the team of Sikiric et al. point toward a possible interaction between BPC-157 and intracellular signaling systems tied to vascular growth through angiogenic pathways and to inflammatory control through the dampening of pro-inflammatory cascades.(1) TB-500 appears to be another synthetic peptide with a sequence that mimics the endogenously occurring thymosin beta-4. The molecule has drawn attention for its apparent involvement in cell migration, cytoskeletal arrangement, and inflammatory signaling. Data from cell culture experiments such as those by Maar et al. hint that TB-500 exposure may assist cellular movement and structural organization while also potentially engaging pathways connected to angiogenesis and the regulation of inflammatory mediators.(2) GHK-Cu is a peptide complex made from the tripeptide GHK, composed of glycine, histidine, and lysine, joined to a divalent copper ion (Cu²⁺). Investigators such as Maquart et al. propose that the GHK sequence may arise endogenously as a signal that there is a process causing collagen breakdown, and repair is needed.(3)GHK-Cu is posited to function as a repair-associated signal that may engage fibroblasts, immune cells, enzymes, ion channels, and cell-surface receptors, with reported downstream potential over gene expression. Copper itself may be central to these potential actions, which may include collagen formation, adjustment of inflammatory signaling, and possible antioxidant activity. KPV is a tripeptide made of lysine, proline, and valine, corresponding to the C-terminal segment of alpha-melanocyte-stimulating hormone (α-MSH). Research models by Böhm et al. suggest that KPV may carry much of the anti-inflammatory potential attributed to the larger α-MSH molecule while remaining a comparatively minimal fragment.(4) Potential mechanisms may involve reduction of NF-κB and MAP kinase signaling, and interactions with vasodilators like nitric oxide (NO), thereby possibly lowering pro-inflammatory cytokine output. KLOW Blend and Potential Anti-inflammatory Signaling All four peptides are posited to occupy potentially complementary and partly overlapping positions within inflammatory signaling both inside cells and across the space between them. For example, laboratory work by Santra et al. suggests that TB-500 may reduce inflammation-linked signaling within cultures of developing brain support cells referred to as oligodendrocyte progenitor cells.(5) When such cells encounter stress or injury, they are posited to switch on innate immune routes, particularly Toll-like receptor (TLR) signaling, which may fuel inflammatory activity inside the cell. The authors examined whether TB-500 may soften this signaling and suggested that the peptide may raise levels of miR-146a. This small regulatory RNA molecule may serve as an internal brake on inflammatory routes. As miR-146a climbs, two central TLR signaling proteins named IRAK1 and TRAF6 may fall and consequently may fail to relay inflammatory signals through the cell, including routes tied to NF-κB activation that would otherwise weigh heavily on inflammatory output. Research by Sikiric et al. further suggests that BPC-157 may also engage inflammatory signaling by curbing the infiltration of inflammatory cells in laboratory models.(6) When experimenting with the peptide, the investigators apparently recorded lower readings of biochemical markers associated with inflammation, among them indicators of neutrophil buildup, leukotriene B4, and thromboxane B2 within inflamed cell cultures. This peptide also appeared to adjust immune cell behavior, with reports of heightened macrophage activity that may steer inflammation toward resolution rather than persistence. These outcomes reportedly emerged without direct suppression of specific cytokines such as TNF, which implies a more regulatory character. BPC-157 may "interact with the NO-system, providing endothelium protection," which may indirectly restrain inflammatory amplification by keeping microvascular structure intact. Further experiments by Park et al. indicate that GHK-Cu may also temper inflammatory signaling in macrophages roused by pro-inflammatory triggers and in models of cell injury.(7) Within activated macrophages, GHK-Cu apparently lowered intracellular reactive oxygen species and nudged superoxide dismutase activity back toward baseline. The pro-inflammatory triggers apparently drove up TNF-α and IL-6 release, whereas GHK-Cu apparently pulled both cytokines down. The authors propose that GHK-Cu may have blunted NF-κB activation by reducing the activation of key regulators. KPV may round out the anti-inflammatory profile of the KLOW Blend through a distinct route, as suggested by laboratory work by Dalmasso et al., who posit that KPV may enter epithelial and immune cell cultures through the PepT1 transporter and, once inside, may suppress inflammatory signaling.(8) Specifically, in cultured epithelial cells stimulated with IL-1β, evaluating the peptide alongside KPV apparently slowed the degradation of IκB-α and shortened the window of NF-κB activation, which may indicate a more restrained inflammatory response. The peptide also apparently reduced IL-1β-driven phosphorylation of ERK1/2, JNK, and p38, pointing toward broad dampening of MAP kinase signaling. In parallel, KPV apparently lowered IL-8 output, and in immune cell cultures stimulated with TNF-α it apparently preserved IκB-α while trimming IL-8 messenger RNA. KLOW Blend and Extracellular Matrix Proteins Multiple experiments with each peptide also suggest possible support for the regeneration and repair of extracellular matrix proteins (ECM) such as collagen and other supporting structures within cell cultures. As an example, research on TB-500 by Xu et al. suggests that the peptide may reinforce structural organization in models of recovering tendon fibroblasts.(9) The investigators apparently observed collagen fibers aligned more uniformly along the ligament axis and spaced more evenly in exposed cultures than in control cultures that were not exposed to the peptide. Electron microscopy results also suggested larger collagen fibril diameters, a feature tied to better-supported mechanical properties. These structural shifts apparently coincided with greater tensile strength and stiffness in the recovered tendon structures. On this basis, the researchers posit that TB-500 may support how ligament fibroblasts organize and lay down collagen during repair and thereby support tissue quality. BPC-157 may also assist repair by supporting tendon fibroblasts, as research by Chang et al. reports quickened fibroblast migration and spreading in laboratory studies, both of which are essential for repopulating an injury site.(10) The peptide apparently offered better fibroblast survival under oxidative stress, a condition commonly present in injured tendon cell cultures. At the cellular level, these outcomes were posited to relate to the upregulation of actin fiber formation, which may have a synergistic potential with TB-500. The researchers commented that "F-actin formation as detected by FITC-phalloidin staining was induced in BPC 157-exposed cells. The activation of focal adhesion signaling through phosphorylation of FAK and paxillin is also posited to assist cell attachment and movement within the extracellular matrix and thereby facilitate repair. GHK-Cu may additionally promote collagen synthesis, particularly at the interface between tendon cells and bone cells. Research by Fu et al. suggests that laboratory models exposed to the complex may indicate better-supported bone cell growth around tendon cell grafts and a trend toward greater cell presence inside the graft structure.(11) KPV may also contribute to the collagen and repair dimension of the KLOW Blend by quieting the inflammatory environment that often accompanies tissue damage in culture. Because KPV apparently curbs NF-κB and MAPK signaling and lowers pro-inflammatory cytokine release, it may help create conditions under which fibroblast activity and matrix deposition may continue with less inflammatory interference.(8) Reports on the α-MSH family more broadly also suggest that Lys-Pro-Val may ease fibroblast stress in dermal cell injury models, which points toward a possible supporting role in structural repair.(4) KLOW Blend and Tissue Regeneration Potential Beyond their apparent calming action on inflammatory signaling, the peptides have been posited to support cellular regeneration through varied mechanisms that ultimately reinforce vascularity and the delivery of nutrients to cellular structures. Notably, TB-500 in particular has been posited to favor cellular regeneration by supporting cell mobility and thereby encouraging angiogenesis. Research by Lv et al. suggests that TB-500 may shape cell movement as it binds globular actin (G-actin) and may adjust how actin filaments assemble to plausibly render cells more capable of changing shape, migrating, and organizing into multicellular structures.(12) Such motility is a baseline requirement for sprouting angiogenesis, where vascular cells must advance into hypoxic tissue and arrange themselves into fresh tubes. The peptide reportedly raised cell viability and migration and increased tube formation on matrices, a common laboratory proxy for angiogenic behavior. TB-500 also appeared to lift expression of angiogenesis-linked factors such as VEGFA, angiopoietin-2 (Ang2), and the Tie2 receptor. Mechanistically, the study by Lv et al. posits that TB-500 may drive angiogenesis through a Notch to NF-κB signaling axis. TB-500 may therefore be hypothesized to encourage angiogenesis by pairing a cytoskeleton-linked rise in endothelial motility with signaling shifts that elevate pro-angiogenic programs such as VEGF-A and Ang2/Tie2 through Notch/NF-κB coupling in damaged cellular structures. Further research by Sikiric et al. also suggests that BPC-157 may aid angiogenesis and, in turn, cellular regeneration.(13) The peptide may act indirectly by steadying the vascular setting required for new vessel growth. Across several injury models, the investigators observed that the peptide may work by shielding endothelial cells and preserving vessel patency. Such endothelium protection may set up conditions in which endothelial sprouting and maturation may proceed. At the cellular level, BPC-157 has been linked to the activation of repair-associated signaling routes, including Egr-1 with its regulator NAB2 and FAK–paxillin signaling, which may participate in cell adhesion and migration. The peptide has additionally been associated with normalized NO signaling under both excessive and suppressed NO states, offsetting the consequences of NOS blockade and NO overproduction. Because NO is posited to govern vasodilation, endothelial survival, and angiogenic signaling, this balancing may support perfusion of injured cellular structures and facilitate endothelial activation and vessel remodeling. Additional investigations by Bonfiglio et al. have evaluated whether the KPV peptide may also support the repair of tissue models, specifically examining the potential mediating role of NO, similarly to BPC-157. (14) Specifically, the researchers experimented with laboratory models featuring mechanically induced abrasions and suggest that the peptide may quicken the recovery of the tissues. Specifically, they commented that all models exposed to KPV achieved complete structural regeneration within 60 hours, whereas control models failed to reach full closure in the same period. This reparative action was apparently blocked when a mitigator of nitric oxide synthase was also added to the experiment. Research on GHK-Cu by Mulder et al. likewise suggests that the peptide may upregulate VEGF, raise endothelial cell proliferation, and encourage endothelial migration and tube formation.(15) These actions are posited to also align with the stimulation of angiogenesis. Copper itself may also serve as a required cofactor for several angiogenic enzymes and transcriptional programs, and the GHK peptide appears to deliver copper in a biologically functional form at sites of cellular injury. KLOW (BPC-157 (10mg), KPV (10mg), TB-500 (10mg), and GHK-Cu (50mg)) Blend is available for research and laboratory purposes only. Please review our Terms and Conditions before ordering. References Seiwerth S, Milavic M, Vukojevic J, Gojkovic S, Krezic I, Vuletic LB, Pavlov KH, Petrovic A, Sikiric S, Vranes H, Prtoric A, Zizek H, Durasin T, Dobric I, Staresinic M, Strbe S, Knezevic M, Sola M, Kokot A, Sever M, Lovric E, Skrtic A, Blagaic AB, Sikiric P. Stable Gastric Pentadecapeptide BPC 157 and Wound Healing. Front Pharmacol. 2021 Jun 29;12:627533. doi: 10.3389/fphar.2021.627533. PMID: 34267654; PMCID: PMC8275860. Maar, K., Hetenyi, R., Maar, S., Faskerti, G., Hanna, D., Lippai, B., Takatsy, A., & Bock-Marquette, I. (2021). Utilizing Developmentally Essential Secreted Peptides Such as Thymosin Beta-4 to Remind the Adult Organs of Their Embryonic State-New Directions in Anti-Aging Regenerative Therapies. Cells, 10(6), 1343. https://doi.org/10.3390/cells10061343 Maquart FX, Pickart L, Laurent M, Gillery P, Monboisse JC, Borel JP. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Lett. 1988 Oct 10;238(2):343-6. doi: 10.1016/0014-5793(88)80509-x. PMID: 3169264. Böhm M, Luger TA, Tobin DJ, García-Borrón JC. Melanocortin receptor ligands: new horizons for skin biology and clinical dermatology. J Invest Dermatol. 2006 Sep;126(9):1966-75. doi: 10.1038/sj.jid.5700421. PMID: 16912693. Santra M, Zhang ZG, Yang J, Santra S, Santra S, Chopp M, Morris DC. Thymosin β4 up-regulation of microRNA-146a promotes oligodendrocyte differentiation and suppression of the Toll-like proinflammatory pathway. J Biol Chem. 2014 Jul 11;289(28):19508-18. doi: 10.1074/jbc.M113.529966. Epub 2014 May 14. PMID: 24828499; PMCID: PMC4094061. Sikiric P, Seiwerth S, Rucman R, Turkovic B, Rokotov DS, Brcic L, Sever M, Klicek R, Radic B, Drmic D, Ilic S, Kolenc D, Stambolija V, Zoricic Z, Vrcic H, Sebecic B. Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157. Curr Med Chem. 2012;19(1):126-32. doi: 10.2174/092986712803414015. PMID: 22300085. Park JR, Lee H, Kim SI, Yang SR. The tripeptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget. 2016 Sep 6;7(36):58405-58417. doi: 10.18632/oncotarget.11168. PMID: 27517151; PMCID: PMC5295439. Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, Yan Y, Sitaraman S, Merlin D. PepT1-Mediated Tripeptide KPV Uptake Reduces Intestinal Inflammation. Gastroenterology. 2008 Jan;134(1):166-178. doi: 10.1053/j.gastro.2007.10.026. PMID: 18061177; PMCID: PMC2431115. Xu B, Yang M, Li Z, Zhang Y, Jiang Z, Guan S, Jiang D. Thymosin β4 enhances the healing of medial collateral ligament injury in rats. Regul Pept. 2013 Jun 10;184:1-5. doi: 10.1016/j.regpep.2013.03.026. Epub 2013 Mar 21. PMID: 23523891. Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J Appl Physiol (1985). 2011 Mar;110(3):774-80. doi: 10.1152/japplphysiol.00945.2010. Epub 2010 Oct 28. PMID: 21030672. Fu SC, Cheuk YC, Chiu WY, Yung SH, Rolf CG, Chan KM. Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstruction. J Orthop Res. 2015 Jul;33(7):1024-33. doi: 10.1002/jor.22831. Epub 2015 Apr 10. PMID: 25731775. Lv S, Cai H, Xu Y, Dai J, Rong X, Zheng L. Thymosin‑β 4 induces angiogenesis in critical limb ischemia mice via regulating Notch/NF‑κB pathway. Int J Mol Med. 2020 Oct;46(4):1347-1358. doi: 10.3892/ijmm.2020.4701. Epub 2020 Aug 11. PMID: 32945357; PMCID: PMC7447324. Sikiric P, Seiwerth S, Rucman R, Kolenc D, Vuletic LB, Drmic D, Grgic T, Strbe S, Zukanovic G, Crvenkovic D, Madzarac G, Rukavina I, Sucic M, Baric M, Starcevic N, Krstonijevic Z, Bencic ML, Filipcic I, Rokotov DS, Vlainic J. Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications. Curr Neuropharmacol. 2016;14(8):857-865. doi: 10.2174/1570159x13666160502153022. PMID: 27138887; PMCID: PMC5333585. Bonfiglio V, Camillieri G, Avitabile T, Leggio GM, Drago F. Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial wound healing: role of nitric oxide. Exp Eye Res. 2006 Dec;83(6):1366-72. doi: 10.1016/j.exer.2006.07.014. Epub 2006 Sep 11. PMID: 16965771. Mulder GD, Patt LM, Sanders L, Rosenstock J, Altman MI, Hanley ME, Duncan GW. Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Wound Repair Regen. 1994 Oct;2(4):259-69. doi: 10.1046/j.1524-475X.1994.20406.x. PMID: 17147644. 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.
Melanotan 1 (10mg)
Melanotan 1 is a synthetic peptide similar to the endogenous alpha-melanocyte stimulating hormone (α-MSH).(1) Melanotan 1 comprises 13 amino acids, the same as α-MSH, but differs by only two amino acids from the endogenous peptide hormone. This structural difference is why researchers suggest the synthetic peptide may exert a higher affinity towards the target cells and boast a longer half-life. According to research, the two notable modifications include the substitution of methionine and L-phenylalanine at the fourth and seventh positions with norleucine and D-phenylalanine, respectively.(1) Overview Melanotan 1 appears to mimic the function of the endogenous α-MSH and may bind to the melanocortin receptors to stimulate the production of eumelanin, a photoprotective compound. This eumelanin may protect tissues from any damage induced by UV exposure.(1) Moreover, eumelanin production also reportedly contributes to increasing levels of pigmentation in skin cells. Chemical Makeup Molecular Formula: C78H111N21O19 Molecular Weight: 1646.87 g/mol Other Known Titles: MT1; afamelanotide Research and Clinical Studies Melanotan 1 and The Melanocortin System Melanotan 1 is hypothesized to exert its actions by interacting with melanocortin receptors (MCRs), which are considered to be crucial signaling pathways in widespread biological processes. It is believed that five distinct melanocortin receptors exist, labeled melanocortin 1 receptors (MC1Rs) through melanocortin 5 receptors (MC5Rs), each associated with specific potential roles:(2,3) MC1R: This receptor is thought to reside in melanocytes - a kind of skin cell that may influence skin and hair pigmentation, potentially by promoting melanin synthesis. MC2R: Reportedly located in the adrenal cortex, it is suggested that this receptor may play a role in the production of cortisol. MC3R: Found in various tissues, including the brain and placenta, MC3R has been implicated in regulating appetite and maintaining energy homeostasis. MC4R: Believed to be situated in the central nervous system, particularly within the hypothalamus, it is speculated that MC4R may have an impact on sexual behavior, erectile function, and the balance of energy within the organism. MC5R: While it appears to be expressed across multiple tissues, the precise physiological function of MC5R remains somewhat elusive, though it is speculated to play a role in exocrine processes. Researchers have suggested that Melanotan 1 may exhibit a particular specificity towards MC1R, ostensibly enhancing melanin production, which, in turn, is thought to result in a tanned appearance of the skin tissues. Notably, the peptide is believed to possess a greater affinity for MC1R over α-MSH, suggesting that it might increase melanin production, thereby promoting skin pigmentation even in the absence of sunlight exposure.(4) More specifically, researchers posit that “when Melanotan I activates MC1R, cAMP is produced, and it activates microphthalmia transcription factor (MITF) expression, which induces the expression of enzymes for eumelanin production.” These proposed interactions underscore the complexity of Melanotan 1's mode of action and highlight the need for further investigative research to fully understand its mechanisms and potential implications in certain biological processes. Melanotan 1 and The Melanocortin Type 1 Receptors Melanocortin 1 Receptor (MC1R) is a Gs protein-coupled receptor found on melanocytes.(5) Its activation is considered potentially integral for regulating skin tissue pigmentation and UV resistance by activating adenylyl cyclase and the subsequent generation of cyclic adenosine monophosphate (cAMP). The cAMP signaling pathway potentially enhances melanin production and deposition, which serves as a natural defense against UV penetration and facilitates nucleotide excision repair (NER), a crucial process for potentially removing UV-induced DNA lesions and averting mutagenesis. Researchers posit that the receptor's activation and signaling are modulated by various ligands, including the positive agonist Melanotan 1, which might increase cAMP levels to promote melanogenesis and enhance DNA repair capabilities. This suggests Melanotan 1 may enhance the skin's natural defense mechanisms against UV damage and possibly reduce the risk of skin cell mutagenesis. However, it is also crucial to consider the receptor's polymorphism and how loss-of-function variants are associated with unpigmented skin, UV sensitivity, and a heightened skin tissue damage risk due to impaired melanization and suboptimal DNA repair mechanisms. Furthermore, MC1R's role may extend beyond pigmentation to include potential actions on anti-inflammatory signaling and the genomic stability of melanocytes, underlining the receptor's multifaceted potential in skin function and disease prevention. The potential interplay between MC1R signaling, melanin production, and NER efficiency underscores the potential for targeted research to bolster UV protection. Yet, the potential of such approaches may be contingent upon individual variations in MC1R function and expression, highlighting the need for further research to fully understand and leverage MC1R's protective mechanisms in skin cells.(5) Melanotan 1 and Inflammation Studies suggest that α-MSH and its analogs, such as Melanotan 1, may exert potential anti-inflammatory action. Researchers have exposed murine models to α-MSH analogs to evaluate the impact of the peptide on tissue inflammation in cases of liver fibrosis through various biomolecular techniques.(6) The study suggested that peptide analogs may reverse the established liver fibrosis and may also mitigate the upregulation of fibrogenic and proinflammatory gene expressions triggered by fibrosis induction. This suggests that analogs may potentially influence the fibrotic process by modulating the expressions of genes involved in fibrogenesis and inflammation. One possible mechanism of action for such potentially protective actions against liver fibrosis may be the modulation of matrix metalloproteinase (MMP) activity and the apparent inactivation of tissue inhibitors of matrix metalloproteinase (TIMP). MMPs are considered to play a crucial role in the degradation of the extracellular matrix, and their activity is posited to be intricately balanced with TIMPs. Researchers have observed that peptide analogs may significantly increase MMP activity while attenuating the activation of α-smooth muscle actin (α-SMA) and cyclooxygenase-2 (COX-2), markers associated with inflammation and fibrogenesis. Furthermore, α-MSH analogs like Melanotan 1 appear to downregulate the mRNA expressions of liver transforming growth factor β1 (TGF-β1), collagen α1, and various cell adhesion molecules, which are posited to be key players in the progression of fibrosis. It is also noteworthy that analogs may have a role in suppressing the expression of COX-2 and cell adhesion molecules, suggesting a potential anti-inflammatory pathway through which Melanotan 1 and similar compounds may exert anti-fibrogenic actions.(6) Melanotan 1 Peptide and Erythropoietic Porphyria Three clinical trials(6) were conducted to examine Melanotan's action on erythropoietic porphyria. In each of the three trials, research models were divided into an experimental and control group: the experimental group was exposed to the peptide, and the control group was exposed to a placebo. This exposure was routinely conducted every two months, and results were monitored for 180 days. The researchers documented the number of hours the research models were exposed to direct sunlight and pain perception during the UV exposure. The outcome of this study was that the experimental peptide group appeared to be able to spend more time in sunlight with little to no pain (approximately 64 hours) compared to the control group, who were exposed to a placebo (approximately 40 hours). Melanotan 1 and UV Radiation The main aim of this study was to understand the peptide's mechanism of action when introduced in combination with UV-B light or sunlight. The study was divided into three phase 1 clinical trials. In the first study, 50% of the cohort were presented with the peptide, and 50% were presented with a placebo for 10 days. In the second study, 58% were exposed to UV irradiation, and 42% were exposed to UV radiation. The final study was conducted in a 50/50 split, where 50% were exposed to the peptide and 50% to a placebo. Following sunlight exposure, the results were analyzed. Researchers reported that the results across all three trials indicated that the peptide may have a positive correlation with exposure and melanin production, as observed on a cellular level and in the relative tanning gradation. Melanotan 1 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 16154396, Scenesse; [cited 2024 Apr. 2]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Scenesse Cai, M., & Hruby, V. J. (2016). The Melanocortin Receptor System: A Target for Multiple Degenerative Diseases. Current protein & peptide science, 17(5), 488–496. https://doi.org/10.2174/1389203717666160226145330 Ji, L. Q., Hong, Y., & Tao, Y. X. (2022). Melanocortin-5 Receptor: Pharmacology and Its Regulation of Energy Metabolism. International journal of molecular sciences, 23(15), 8727. https://doi.org/10.3390/ijms23158727 Mun, Y., Kim, W., & Shin, D. (2023). Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects. International journal of molecular sciences, 24(15), 12152. https://doi.org/10.3390/ijms241512152 Wolf Horrell EM, Boulanger MC, D'Orazio JA. Melanocortin 1 Receptor: Structure, Function, and Regulation. Front Genet. 2016 May 31;7:95. doi: 10.3389/fgene.2016.00095. PMID: 27303435; PMCID: PMC4885833. Lee TH, Jawan B, Chou WY, Lu CN, Wu CL, Kuo HM, Concejero AM, Wang CH. Alpha-melanocyte-stimulating hormone gene therapy reverses carbon tetrachloride induced liver fibrosis in mice. J Gene Med. 2006 Jun;8(6):764-72. doi: 10.1002/jgm.899. PMID: 16508911. Dorr RT, Ertl G, Levine N, Brooks C, Bangert JL, Powell MB, Humphrey S, Alberts DS. Effects of a superpotent melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers. Arch Dermatol. 2004 Jul. https://pubmed.ncbi.nlm.nih.gov/15262693/ 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.
GHK Basic (Tripeptide-1) (200mg)
GHK Basic is a tripeptide composed of glycine, histidine, and lysine amino acids. It is a naturally occurring tripeptide in plasma, urine, saliva, and other fluids. GHK is produced by various cells, including fibroblasts, lymphocytes, and macrophages. It is also found in high concentrations in platelets and certain tissues, such as the liver and brain. GHK appears to have a high affinity to copper and may regulate numerous biological processes, including wound healing, tissue repair, and immune response. GHK also has been suggested to have a role in regulating ion channels, enzymes, receptors, and gene expression. The levels of GHK appear to fluctuate over the course of cell lifespan, and it has been suggested that these changes contribute to cell aging. This may result in impaired tissue repair and regeneration and a decline in immune function. GHK may stimulate collagen production and play a role in wound healing and skin cell function. GHK may also have antioxidant and anti-inflammatory characteristics. Chemical Makeup Molecular formula: C14H24N6O4 Molecular weight: 340.4 g/mol Other known titles: Glycyl-L-histidyl-L-lysine, Tripeptide 1, NSC 379527, Copper peptide Research and Clinical Studies GHK Basic Peptide and Wound Healing GHK has been primarily studied for its potential in wound healing. One clinical study evaluated GHK (its copper-bound version) in research models of diabetic neuropathic ulcers.(1) The models were subjected to a wound care protocol, and GHK was reported to increase ulcer closure compared to the vehicle. Larger plantar ulcers had a more pronounced enhancement of closure, with the incidence of ulcer infections reportedly lower in the GHK group. The scientists highlighted that the “incidence of ulcer infections was significantly lower (7% incidence compared with 34% for vehicle, p < 0.05) in the plantar ulcers treated immediately after debridement.” Animal studies also suggest the potential of GHK in rapid wound healing. A study compared the actions of GHK on wound healing with control (not exposed to GHK) wounds in rabbits.(2) The wounds were evaluated daily, and planimetry was performed on days 7, 14, 21, and 28 to measure the unhealed wound area and the percentage of total wound healing. Results indicated that the GHK group exhibited greater neutrophil and vessel counts than the control group. The research team proposed that the peptide in question might potentially accelerate the recovery of wounds and the development of granular tissue, which refers to the new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the recovery process. It is hypothesized that this action might be associated with increased activity of antioxidant enzymes—proteins that help protect cells from damage due to oxidative stress. Additionally, there might be an improvement in vascular development, meaning the formation and growth of new blood vessels within the wound, which is deemed crucial for delivering nutrients and oxygen that support tissue repair. Another study also aimed to evaluate the actions of GHK on the recovery of ischemic open wounds in rats.(3) The GHK group appeared to exhibit a significant decrease in wound area compared to the control group. Wounds exposed to GHK were reported to contain lower concentrations of the pro-inflammatory markers, including tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). Each of these markers plays a role in the inflammatory response and tissue remodeling, indicating that GHK may mitigate inflammation and tissue degradation in ischemic wound environments. In subsequent studies using typical murine models and those modified to simulate diabetic conditions, dressings made of collagen and enriched with GHK appeared to enhance the recuperation of wounds. The data indicates that by the end of the third week, wounds addressed with films containing biotinylated GHK approached near-total closure at 99.39%, which may represent a notable improvement over the 69.49% closure rate seen with control films. Moreover, these GHK-exposed wounds appeared to have exhibited higher concentrations of glutathione and ascorbic acid. These molecules are important antioxidants that may contribute to tissue repair. There was also a possible increase in epithelialization, which is the process of renewing the outer layer of the skin tissue in experimental models. Additionally, there may have been a stimulation of collagen production, which is vital for the skin's structural integrity, enhanced activity of fibroblasts—cells crucial for wound recovery —and an increase in mast cell activation, which plays a role in the inflammatory responses. GHK Basic Peptide and Skin Cells GHK may exhibit implications within the development of creasing and wrinkling along the stratum corneum of the skin barrier by potentially influencing the upregulation of collagen production.(5) It has been hypothesized that the underlying mechanisms for this observed phenomena may involve the presence of the tripeptide sequence Gly-His-Lys as a fragment typically released during the hydrolysis process of collagen. Hydrolysis of collagen, which occurs when collagen fibers are broken down, often results from tissue damage or degradation. Scientists have posited that "the presence of a GHK triplet in the alpha 2(I) chain of type I collagen suggests that the tripeptide might be liberated by proteases at the site of a wound and exert in situ healing." These peptide fragments might play a role in cellular signaling, particularly influencing fibroblasts, which are cells deemed critical for synthesizing new collagen fibers. This signaling is essential as it appears to trigger the fibroblasts to begin synthesizing collagen, thus contributing to tissue repair and regeneration. GHK may also stimulate elastin and glycosaminoglycans. Elastin is another vital protein contributing to the skin's elastic properties, while glycosaminoglycans are long polysaccharide molecules that play a role in maintaining and supporting the extracellular matrix. Together, these components are considered essential for maintaining the skin's structural integrity and functional characteristics. Another clinical study reported that GHK appeared to improve collagen production and stimulated dermal keratinocyte proliferation under specific research conditions.(6) The studies also reported an apparent increase in skin thickness, improved skin hydration, and smoothing by stimulating collagen synthesis, skin elasticity, and increased production of type 1 collagen. A further clinical study evaluated the efficacy of GHK for managing CO2 laser-resurfaced skin - a procedure that removes the epidermis and heats the derma.(7) A cohort of 13 models were randomly assigned to receive either post-procedure skin regimens with or without GHK. While there was no statistically significant difference in erythema resolution, both groups were reported to experience improvement in wrinkles and overall skin quality. Furthermore, models exposed to the GHK substance reported higher satisfaction with post-exposure improvement in overall skin quality than those without. GHK Basic Peptide and Inflammation, Oxidative Stress GHK may have antioxidant and anti-inflammatory potential that protect cells from damage caused by active radicals and lipid peroxidation. Studies report that the peptide may inactivate damaging free radicals that are by-products of lipid peroxidation and UV-light exposure.(8) The specific radicals reported by the researchers included 4-hydroxynoneal, acrolein, malondialdehyde, and others. Furthermore, GHK may completely block the oxidation of low-density lipoproteins. Additionally, GHK was suggested to have potential action in reducing iron release from ferritin, a lipid peroxidation catalyst. Researchers report that GHK may reduce the formation of iron complexes in damaged tissues and thus reduce inflammation.(9) The study suggested that GHK acts by binding to the channels of ferritin involved in the iron release and may physically reduce the release of -Fe by a reported 87%, which may prevent inflammation and oxidation in damaged tissues. The anti-inflammatory potential of GHK may also extend to organs such as the lungs. One animal model study investigated the actions of GHK on lipopolysaccharide-induced lung inflammation in mice.(10) The study suggested that GHK may reduce the production of reactive oxygen species and inflammatory cytokines while increasing the activity of antioxidant enzymes. It also may suppress the activation of NF-κB and p38 MAPK signaling pathways, decreasing TNF-1 and IL-6 production. Furthermore, the researchers reported that GHK appeared to attenuate lung histological alterations and reduce inflammatory damage in the lungs of mice with lung damage. The scientists reported that the peptide “suppressed the infiltration of inflammatory cells into the lung parenchyma in LPS-induced ALI in mice.” GHK may also help reduce the oxidative stress caused by smoking. Scientists reported that GHK appeared to inhibit oxidative stress in alveolar epithelial cells by upregulating Nrf2 expression.(11) A study investigated the potential of GHK to reduce levels of reactive oxygen species in cell cultures.(12) The researchers suggested that the GHK action on the signal of hydroxyl radicals may be stronger than those of other antioxidative, endogenous peptides, such as carnosine and reduced glutathione. GHK Basic peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Mulder, G. D., Patt, L. M., Sanders, L., Rosenstock, J., Altman, M. I., Hanley, M. E., & Duncan, G. W. (1994). Enhanced healing of ulcers in patients with diabetes by treatment with glycyl-l-histidyl-l-lysine copper. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 2(4), 259–269. https://doi.org/10.1046/j.1524-475X.1994.20406.x Gul, N. Y., Topal, A., Cangul, I. T., & Yanik, K. (2008). The effects of tripeptide copper complex and helium-neon laser on wound healing in rabbits. Veterinary dermatology, 19(1), 7–14. https://doi.org/10.1111/j.1365-3164.2007.00647.x Canapp, S. O., Jr, Farese, J. P., Schultz, G. S., Gowda, S., Ishak, A. M., Swaim, S. F., Vangilder, J., Lee-Ambrose, L., & Martin, F. G. (2003). The effect of tripeptide-copper complex on healing of ischemic open wounds. Veterinary surgery : VS, 32(6), 515–523. https://doi.org/10.1111/j.1532-950x.2003.00515.x Alven, S., Peter, S., Mbese, Z., & Aderibigbe, B. A. (2022). Polymer-Based Wound Dressing Materials Loaded with Bioactive Agents: Potential Materials for the Treatment of Diabetic Wounds. Polymers, 14(4), 724. https://doi.org/10.3390/polym14040724 Maquart, F. X., Pickart, L., Laurent, M., Gillery, P., Monboisse, J. C., & Borel, J. P. (1988). Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS letters, 238(2), 343–346. https://doi.org/10.1016/0014-5793(88)80509-x Abdulghani, A. A., Sherr, A., Shirin, S., Solodkina, G., Tapia, E. M., Wolf, B., & Gottlieb, A. B. (1998). Effects of creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin-A pilot clinical, histologic, and ultrastructural study. Disease Management and Clinical Outcomes, 4(1), 136-141. Miller, T. R., Wagner, J. D., Baack, B. R., & Eisbach, K. J. (2006). Effects of copper tripeptide complex on CO2 laser-resurfaced skin. Archives of facial plastic surgery, 8(4), 252–259. https://doi.org/10.1001/archfaci.8.4.252 Cebrián, J., Messeguer, A., Facino, R. M., & García Antón, J. M. (2005). New anti-RNS and -RCS products for cosmetic treatment. International journal of cosmetic science, 27(5), 271–278. https://doi.org/10.1111/j.1467-2494.2005.00279.x Miller, D. M., DeSilva, D., Pickart, L., & Aust, S. D. (1990). Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation. Advances in experimental medicine and biology, 264, 79–84. https://doi.org/10.1007/978-1-4684-5730-8_11 Park, J. R., Lee, H., Kim, S. I., & Yang, S. R. (2016). The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget, 7(36), 58405–58417. https://doi.org/10.18632/oncotarget.11168 Zhang, Q., Yan, L., Lu, J., & Zhou, X. (2022). Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway. Frontiers in molecular biosciences, 9, 925700. https://doi.org/10.3389/fmolb.2022.925700 Sakuma, S., Ishimura, M., Yuba, Y., Itoh, Y., & Fujimoto, Y. (2018). The peptide glycyl-ʟ-histidyl-ʟ-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals. International journal of physiology, pathophysiology and pharmacology, 10(3), 132–138. 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.