Peptides
PT-141 (Bremelanotide) (10mg)
Bremelanotide, which is also commonly known by PT-141, is a cyclic synthetic peptide composed of seven amino acids.(1) PT-141 synthetic peptide appears to be agonistic to melanocortin receptors, which is similar to the natural hormone alpha-MSH.(2) It is a by-product of the metabolism of another synthetic analog called melanotan II. Initial studies suggested that melanocortin hormones may regulate various physiological functions. When test animals were presented with the isolated hormone, it was reported to present elevated reproductive functions, which is one of the primary areas of research currently being conducted on PT-141 peptide. Overview Studies have suggested that PT-141 shows agonistic properties towards melanocortin receptors, namely MC3R and MC4R, which may result in elevated reactions in the central nervous system. MC3R, which appears to be primarily expressed in the brain, especially within the hypothalamus, might play a role in energy homeostasis. It has been hypothesized by research teams examining melanocortin receptor activity, that MC3R may potentially modulate the actions of other melanocortin receptors in this area. Moreover, MC3R might influence feeding behavior, possibly impacting appetite and food intake, and is thought to be involved in various metabolic processes, including the potential regulation of glucose and lipid metabolism.(3) On the other hand, MC4R is believed to be essential in appetite control. When activated in the brain, it is considered to contribute to appetite regulation. MC4R is also posited to have a role in energy expenditure, with its activation possibly leading to an increase in energy output, which could contribute to weight reduction. This receptor has also been tentatively linked to reproductive function, especially in the potential regulation of the function of penile tissues and overall reproductive behavior.(4) In publically available study, it was suggested by researchers that following binding with MC3R and MC4R receptors, the peptide appeared to lead to the activation of the neurons found in the hypothalamus, leading to apparently increased immunoreactivity.2() Neurons in the surrounding region of the central nervous system may also be stimulated as they intake the chemicals which then reportedly lead to sexual arousal in murine models. PT-141 Chemical Makeup Molecular formula: C50H68N14O10 Molecular weight: 1025.18 g/mol Other Known Titles: Bremelanotide Research and Clinical Studies PT-141 Peptide Initial Studies This early 2000 study was conducted to understand the potential of PT-141 peptide in murine models. The murine models were used as the subject in this study to determine how the peptide may impact their sexual behavior.(5) After presentation, it was reported that the female rats appeared to exhibit elevated sexual desire without any increase/decrease in the sexual pace, lumbar lordosis, or any other sexually-related behaviors. After analysis, it was suggested by the researchers that the peptide did not directly impact a generalized motor activation, instead it may have potential selective pharmacological impact that may stimulate the central nervous system, mainly the melanocortin receptor activities, which might result in elevated sexual arousal. More specifically, the researchers commented that “ The ability of PT-141 to enhance solicitation in two distinctive testing environments indicates that the effect is selective and stable, and suggests that central melanocortin systems are part of the neurochemical network that evokes appetitive sexual behavior in female rats.”(5) PT-141 Peptide and Arousal The potential activation of the MC4R by PT-141 may also upregulate the production of vasodilators like nitric oxide (NO) in penile tissues, leading to improved erection potential, as suggested by research.(6) The peptide is posited to be a metabolite of Melanotan-2 (MT-II), and both appear to activate the same receptors. For example, it has been posited that melanocortin agonists might lead to concentration-related increases in cavernosal pressure. SHU 9119, an agent that is possibly a non-selective antagonist of MC3R and MC4R, appears not to have had a significant impact on cavernosal or systemic blood pressure. However, it seems to have negated the increases in cavernosal pressure that melanocortin agonists potentially induced. This same agent, SHU 9119, also appears to have inhibited the depressor response that was probably produced by melanocortin agonists. Moreover, when a combination containing phentolamine mesylate, papaverine, and PGE1 was introduced directly into the cavernosal tissue, it reportedly led to a 4-fold increase in cavernosal pressure. The study also hypothesized the role of the NO-cyclic GMP-dependent pathway in relation to the melanocortin agonists-induced increases in cavernosal pressure. This was done by performing a bilateral transection of the pudendal nerves and inhibiting NO synthase using L-NAME. The results indicate that either removing the pudendal nerves or pretreating with L-NAME may negate the increases in intracavernosal pressure that melanocortin agonists likely induced in the anesthetized murine models. From the gathered data, it was tentatively inferred that the activation of central melanocortin receptors by melanocortin agonists might lead to an increase in cavernosal pressure, probably achieved through the neuronal release of NO.(6) PT-141 Peptide and the Central Nervous System Studies on PT-141 have aimed to understand the potential of the peptide in the central nervous system (CNS) and possibly also some brain regions.(7) One study was carried out in murine models with rich levels of the female reproductive hormones. Researchers mainly focused on both the sexual behaviors of the rats i.e., appetitive behaviors such as increased pace and agitation, and consummatory behaviors such as lordosis. In this study, the rats were presented with the peptide, which apparently resulted in increased appetitive behavior of solicitation without impacting the sexual pace or lordosis. The actions of PT-141 were noted following both peripheral introductions and introduction directly into the lateral ventricles or medial preoptic area (mPOA), but possibly not the ventromedial hypothalamus. The mPOA may be a significant region for displaying appetitive sexual behaviors in models across various species, though this theory is still being explored. When PT-141 was introduced peripherally, it appeared to activate the mPOA and other hypothalamic and limbic brain regions possibly associated with sexual behavior. The study hypothesizes that PT-141 might function by potentially activating dopamine terminals located in the mPOA, but further research is needed to confirm this. The researchers commented that the peptide “appears to possess the behavioral, pharmacological, and neuroanatomical specificity required” to potentially influence sexual function.(7) To gain a deeper understanding of these mechanisms, a study was conducted using psychometric, functional neuroimaging, and hormonal analyses. This study was a randomized, double-blinded, placebo-controlled, crossover clinical investigation that aimed to evaluate the impact of MC4R agonism on sexual brain processing. The results indicated that MC4R agonists like PT-141 might elevate sexual desire for up to 24 hours compared to a placebo. Furthermore, during the functional neuroimaging phase, it appeared that MC4R agonism possibly amplified activity in the cerebellar and supplementary motor areas while possibly deactivating the secondary somatosensory cortex, specifically when the subjects were exposed to erotic stimuli, in contrast to the placebo. Moreover, MC4R agonists were hypothesized to boost the functional connectivity between the amygdala and the insula when exposed to erotic stimuli, again compared to the placebo. Based on these observations, researchers posited that MC4R agonists might augment sexual brain processing. This research offers further insights into the mechanisms through which MC4R agonists like PT-141 might influence sexual behavior, shedding light on the ongoing exploration of this class of peptides.(8) PT-141 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Pfaus, J., Giuliano, F., & Gelez, H. (2007). Bremelanotide: an overview of preclinical CNS effects on female sexual function. The journal of sexual medicine, 4 Suppl 4, 269–279. https://doi.org/10.1111/j.1743-6109.2007.00610.x National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 9941379, Bremelanotide. Retrieved August 10, 2023 from https://pubchem.ncbi.nlm.nih.gov/compound/Bremelanotide. Molinoff, P. B., Shadiack, A. M., Earle, D., Diamond, L. E., & Quon, C. Y. (2003). PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Annals of the New York Academy of Sciences, 994, 96–102. https://doi.org/10.1111/j.1749-6632.2003.tb03167.x Renquist, B. J., Lippert, R. N., Sebag, J. A., Ellacott, K. L., & Cone, R. D. (2011). Physiological roles of the melanocortin MC₃ receptor. European journal of pharmacology, 660(1), 13–20. https://doi.org/10.1016/j.ejphar.2010.12.025 Adan, R. A., Tiesjema, B., Hillebrand, J. J., la Fleur, S. E., Kas, M. J., & de Krom, M. (2006). The MC4 receptor and control of appetite. British journal of pharmacology, 149(7), 815–827. https://doi.org/10.1038/sj.bjp.0706929 Pfaus, J. G., Shadiack, A., Van Soest, T., Tse, M., & Molinoff, P. (2004). Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proceedings of the National Academy of Sciences of the United States of America, 101(27), 10201–10204. https://doi.org/10.1073/pnas.0400491101 Vemulapalli, R., Kurowski, S., Salisbury, B., Parker, E., & Davis, H. (2001). Activation of central melanocortin receptors by MT-II increases cavernosal pressure in rabbits by the neuronal release of NO. British journal of pharmacology, 134(8), 1705–1710. https://doi.org/10.1038/sj.bjp.0704437 Thurston, L., Hunjan, T., Mills, E. G., Wall, M. B., Ertl, N., Phylactou, M., Muzi, B., Patel, B., Alexander, E. C., Suladze, S., Modi, M., Eng, P. C., Bassett, P. A., Abbara, A., Goldmeier, D., Comninos, A. N., & Dhillo, W. S. (2022). Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder. The Journal of clinical investigation, 132(19), e152341. https://doi.org/10.1172/JCI152341 Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
BPC-157 & TB-500 & GHK-Cu Blend (70mg)
BPC-157 appears to be a distinct synthetic peptide composed of fifteen amino acids and is thought to originate from a fragment of a gastric protein. However, the specific protein has not yet been established. Research models indicate that BPC-157 may interact with intracellular signaling systems relevant to vascular growth via angiogenic signaling and inflammatory regulation via attenuation of pro-inflammatory pathways. (1) TB-500 is a synthetic peptide identical to the 43 amino acid structure of the endogenous thymosin beta-4, studied for its involvement in cellular migration, cytoskeletal organization, and inflammatory signaling. In vitro studies suggest that exposure to TB-500 may support cell movement and structural coordination, and may also participate in signaling pathways linked to angiogenesis and modulation of inflammatory mediators. (2) GHK-Cu is a peptide complex consisting of the tripeptide GHK (glycine, histidine, and lysine), bound to a divalent copper ion (Cu²⁺). Researchers suggest that the GHK sequence may occur endogenously, specifically being released by cells, including fibroblasts, macrophages, and lymphocytes, during damage, as a result of collagen breakdown. (3) Thus, GHK-Cu is posited to act as a repair signal, capable of interacting with enzymes, ion channels, and cell-surface receptors, with reported downstream potential on gene expression. The presence of copper may be central to these observations, including collagen synthesis, modulation of inflammatory signaling, and antioxidant potential. These peptides may have partially overlapping but also complementary actions, supporting the hypothesis that combined exposure may positively affect inflammatory signaling. In addition, the peptides may all play some role in the regeneration of different cells, possibly supporting factors like vascular formation and cellular behavior. Chemical Makeup Other Known Titles BPC-157: C62H98N16O22 TB-500: C212H350N56O78S GHK-Cu: C14H23CuN6O4 Molecular Weight: BPC-157:5 g/mol TB-500: 4963 g/mol GHK-Cu: 38 g/mol Molecular Formula: BPC-157: Body Protection Compound-157 TB-500: Synthetic Thymosin Beta-4 GHK-Cu: glycyl-L-histidyl-L-lysine-copper 2+ Research and Clinical Studies Anti-inflammatory Signaling Research on BPC-157 & TB-500 & GHK-Cu All three peptides appear to play some potentially complementary and partially overlapping roles in inflammatory signaling inside and in between cells. Notably, all three appear to have a positive action on toning down inflammatory processes. For example, research conducted in laboratory settings by Santra et al. suggests that TB-500 may lower inflammation-related signaling inside cell cultures of developing brain support cells called oligodendrocyte progenitor cells. (4) After cell stress or injury, these cells are posited to activate innate immune pathways, especially Toll-like receptor (TLR) signaling, which may drive inflammatory responses inside the cell. The authors research whether TB-500 may tone down this signaling and suggest that the peptide may increase the level of miR-146a, a small regulatory RNA molecule whose role may be to act as an internal brake on inflammatory signaling pathways. When miR-146a levels rise, two key TLR signaling proteins, IRAK1 and TRAF6, may decrease, and thus they may not transmit inflammatory signals inside the cell, including pathways linked to NF-κB activation, which would otherwise play a major role in inflammatory signaling. Furthermore, research by Sikiric et al. suggests that BPC-157 may also interact with inflammatory signaling, specifically by attenuating inflammatory cell infiltration in research models. (5) Apparently, the researchers observed lower levels of biochemical markers linked to inflammation, including markers of neutrophil accumulation, leukotriene B4, and thromboxane B2 in inflamed cellular cultures. This peptide also appeared to modulate immune cell behavior, with reports of increased macrophage activity, which may support resolution rather than persistence of inflammation. Importantly, these implications were observed without direct immunosuppression of specific cytokines such as TNF, implying a more regulatory mode of action. BPC-157 may “interact with the NO-system [nitric oxide system], providing endothelium protection”, which may indirectly limit inflammatory amplification by preserving microvascular integrity. Last but not least, experiments by Park et al. suggest that GHK-Cu may also tone down inflammatory signaling in macrophages activated by pro-inflammatory triggers and in lung cell injury models. (6) In activated macrophages, GHK-Cu apparently lowered intracellular reactive oxygen species and restored superoxide dismutase activity toward control values. The pro-inflammatory triggers apparently increased TNF-α and IL-6 release, while GHK-Cu apparently reduced both cytokines. Mechanistically, the authors suggest that GHK-Cu may have suppressed NF-κB activation by reducing the activation of key regulators. The researchers did not notice significant action on ERK1/2, JNK1/2, or NO secretion. In the lung cell cultures, the peptide complex apparently reduced edema, inflammatory cell infiltration, and overall histologic injury scores. The researchers also observed reductions in TNF-α, IL-6, total cell counts, neutrophils, MPO activity, and markers of alveolar permeability. Cellular Regeneration Potential of BPC-157 & TB-500 & GHK-Cu In addition to their potentially positive actions on toning down inflammatory signaling, all three peptides have been posited to also support cellular regeneration via different mechanisms that ultimately support vascularity and nutrient delivery to the cellular structure. Notably, TB-500 has been posited to exert positive actions on cellular regeneration by interacting with cellular mobility and thus supporting angiogenesis. Research by Lv et al. suggests that TB-500 may interact with cell movement as it binds globular actin (G-actin) and may modulate how actin filaments assemble to plausibly make endothelial cells more able to change shape, migrate, and form multicellular structures. (7) That type of motility is a basic requirement for sprouting angiogenesis, where endothelial cells need to move into hypoxic tissue and organize into new tubes. The researchers suggest that during evaluation, the peptide increased cell viability and migration and increased tube formation on matrices, which is commonly exposed to research models as a lab proxy for angiogenic behavior. In parallel, TB-500 appeared to increase expression of angiogenesis-linked factors, including VEGFA, angiopoietin-2 (Ang2), and the Tie2 receptor. Mechanistically, the study posits that TB-500 may push angiogenesis through a Notch to NF-κB signaling axis. Thus, TB-500 may be hypothesized to support angiogenesis by combining a cytoskeleton-linked increase in endothelial motility with signaling changes that raise pro-angiogenic programs (VEGF-A and Ang2/Tie2) via Notch/NF-κB coupling in damaged cellular structure. Research by Sikiric et al. also suggests that BPC-157 may also support angiogenesis and thus cellular regeneration. (8) More specifically, this peptide may act indirectly by stabilizing the vascular environment needed for new vessel growth. Across multiple injury models, the researchers have observed that the peptide may work by protecting endothelial cells and preserving vessel patency. Such endothelium protection creates conditions in which endothelial sprouting and maturation may occur. At the cellular level, BPC-157 has been linked to activation of repair-associated signaling pathways, including Egr-1 with its regulator NAB2, and FAK–paxillin signaling, which are potentially involved in cell adhesion and migration. These processes are essential for endothelial movement through the extracellular matrix during capillary sprouting. The peptide has also been associated with normalised NO signaling under both excessive and suppressed NO states, counteracting the implications of NOS blockade and NO overproduction. Because NO regulates vasodilation, endothelial survival, and angiogenic signaling, this balancing may support perfusion of injured cellular structures and facilitate endothelial activation and vessel remodeling during repair. Mechanistically, research on GHK-Cu by Mulder et al. also suggests that the peptide may upregulate VEGF, increase endothelial cell proliferation, and promote endothelial migration and tube formation. (9) These actions are consistent with stimulation of angiogenesis. At the same time, copper itself is 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. Collagen Repair Potential of BPC-157 & TB-500 & GHK-Cu Multiple experiments with each of the three peptides also suggest that they may support the regeneration and repair of collagen and other supporting structures in cell cultures such as tendon fibroblasts. For example, research on TB-500 by Xu et al. may support the structural organization in models of recovering tendon fibroblasts. (10) Apparently, the researchers observed collagen fibers that were more uniformly aligned along the ligament axis and more evenly spaced than in controls. Electron microscopy suggested larger collagen fibril diameters, a feature linked to better-supported mechanical properties. These structural changes apparently were accompanied by higher tensile strength and stiffness of the recovered tendon structures. Based on this data, the researchers posit that TB-500 may support how ligament fibroblasts organize and deposit collagen during repair, improving tissue quality. BPC-157 may also support repair by supporting tendon fibroblasts, as the research by Chang reports accelerated fibroblast migration and spreading in laboratory studies, both of which are essential for repopulating an injury site. Apparently, the peptide may also have better supported fibroblast survival under oxidative stress, a condition commonly present in injured tendon cell cultures. At the cellular level, these implications were posited to be related to the upregulation of actin fiber formation, as the researchers commented that “F-actin formation as detected by FITC-phalloidin staining was induced in BPC 157” exposed cells. Moreover, the activation of focal adhesion signaling through phosphorylation of FAK and paxillin is also posited to aid cell attachment and movement within the extracellular matrix, thus ultimately facilitating repair. GHK-Cu may also promote collagen synthesis, particularly in the binding between tendon cells and bone cells. Research by Fu et al. suggests that research models exposed to the peptide complex may have better bone formation around tendon cell grafts and a trend toward higher cell presence within the graft structure itself. Overall, all three peptides appear to exert potential positive actions linked to cellular repair and integrity, including anti-inflammatory signaling, angiogenesis, collagen synthesis, and more. Unfortunately, research investigating the simultaneous experimentation with all three compounds has yet to be conducted. BPC-157 & TB-500 & GHK-Cu 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. 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. 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. 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. 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. 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.
Tripeptide-29 (200mg)
Tripeptide-29 is a small, naturally occurring amino-acid peptide, one of the primary building blocks for collagen protein.(1) Collagen is a major component of the extracellular matrix, the network of proteins and fibers comprising connective tissues. It is considered responsible for providing structure and support to cellular complexes. Researchers suggest Tripeptide-29 may have the potential to stimulate collagen synthesis and promote the formation of collagen fibers. In addition to its possible role in collagen synthesis, Tripeptide-29 may have other biological functions. For example, research studies have hypothesized its potential as an antioxidant, which might help protect cells from oxidative stress and damage. It may also exhibit anti-inflammatory, anti-fibrotic, and anti-melanogenic characteristics. Chemical Makeup Molecular Formula: C12H19N3O5 Molecular Weight: 285.3 g/mol Other Known Titles: Glycylprolylhydroxyproline Research and Clinical Studies Tripeptide-29 and Collagen Integrity Tripeptide-29 may be a major contributor to the stability of type 1 collagen molecules. Studies suggest that the OH group of Hyp in Tripeptide-29 may contribute to the formation of favorable interatomic interactions.(2) The researchers propose that Tripeptide-29 as a monomer may enhance the stability of collagen and collagen microfibrils. Studies also suggest that the presence of Tripeptide-29 as a part of the sequence in collagen may significantly reduce UV-related damage and lower the degradation rate when exposed to intensive radiation.(3) A study conducted on dermal fibroblasts reported that hydrolyzed type 1 collagen tripeptides exhibited promising potential in reducing oxidative stress and damage.(4) As previously noted, Tripeptide-29 appears to be the primary tripeptide that forms when hydrolyzing type 1 collagen. The hydrolysate showed potential in reducing the build-up of advanced glycation end products (AGEs), reportedly preventing the production of denatured collagen and lowering levels of reactive oxygen species. The glycation process refers to sugar molecules bonding with proteins, potentially speeding up skin cell aging by altering its mechanical properties and stability. Ultimately, the scientists suggested that tripeptide-29 “might improve [cell aging] phenotypes via the inhibition of glycation and oxidative stress, leading to a delay in cellular aging.” From an in vitro perspective, the study explored the mechanisms underpinning the observed action. It was suggested that Tripeptide-29 may reduce the production of AGEs and denatured collagen while inhibiting the activity of matrix metalloproteinases (MMPs) and enhancing collagen 1 levels in dermal fibroblasts. These results suggest that Tripeptide-29 may mitigate cell aging by preserving collagen integrity and inhibiting processes that degrade the skin matrix. Furthermore, it is indicated that Tripeptide-29 might be linked to its smaller peptide size, which is believed to support its skin penetration and bioavailability. Tripeptide-29 and Glucose Control According to researchers, Tripeptide-29 may act as a peptidic inhibitor of dipeptidyl peptidase-IV (DPP-IV) due to its potential to inhibit the hydrolysis of the Pro-Hyp bond.(5) It was considered a moderately competitive inhibitor. The scientists reported that “Gly-Pro-Hyp in the collagen hydrolysates is suggested to be mainly responsible for the DPP-IV inhibition in vitro,” inferring that Tripeptide-29 may contribute to the overall inhibitory action of collagen peptides on DPP-IV. Interestingly, Tripeptide-29 was reportedly not hydrolyzed by DPP-IV, indicating resistance to this specific enzyme. This observation might point to the peptide's stability and efficacy in the presence of this enzyme. Dipeptidyl peptidase-IV (DPP-IV) is a serine peptidase involved in several biological processes.(6) The enzyme is expressed on the surface of various cell types, including immune cells, epithelial cells, and endothelial cells. It is also apparently found in circulation in the liver, kidney, and intestine tissues. DPP-IV cleaves peptide bonds at the N-terminus of dipeptides, tripeptides, and smaller peptides, but not larger peptides or proteins. This specificity means it may act on various substrates, including hormones, neuropeptides, and chemokines. Some of the substrates of DPP-IV include glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY), all of which are suggested to be involved in the regulation of glucose homeostasis and energy metabolism.(7) The cleavage of GLP-1 and GIP by DPP-IV may result in rapid inactivation and clearance from circulation. Inhibiting DPP-IV may upregulate the levels of GLP-1 and GIP, which may lead to an increase in insulin secretion, reduction in glucagon levels, lower blood glucose, and decreased appetite.(8) Tripeptide-29 and Platelet Aggregation Collagen-related peptides that contain a glycine-proline-hydroxyproline repeat motif are considered to be cross-linked through cysteine residues, which may stimulate platelet aggregation and secretion through glycoprotein VI (GPVI) receptors. GPVI is a platelet receptor that scientists believe to be crucial in blood clotting or hemostasis. It is a transmembrane glycoprotein that appears to be primarily expressed on the surface of platelets, which are blood cells involved in blood clotting. GPVI is a member of the immunoglobulin (Ig) superfamily of proteins, comprised of two subunits called alpha and beta. The alpha subunit is considered to contain the collagen-binding site, while the beta subunit is deemed responsible for signaling within the platelet. When the GPVI receptor binds to collagen, it may trigger a series of events that lead to the activation of platelets and the formation of a blood clot. Studies suggest that the non-cross-linked form of glycine-proline-hydroxyproline, or Tripeptide-29, may induce tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase C gamma2 (PLCgamma2) in platelets.(9) This may ultimately stimulate platelet aggregation to stop or prevent bleeding. Overall, the researchers report that Tripeptide-29, “present as a repeat motif, is sufficient to activate the platelet collagen receptor GPVI,” and may stimulate the formation of thrombi to prevent excessive bleeding. Tripeptide-29 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Wiśniewski, K., Artemowicz, B., Lutostańska, A., Maćkowiak, J., & Koziołkiewicz, W. (1994). Central activity of peptide Gly-Pro-Hyp--the main component of collagen degradation products mixture. Acta neurobiologiae experimentalis, 54(1), 33–38. Némethy, G., & Scheraga, H. A. (1986). Stabilization of collagen fibrils by hydroxyproline. Biochemistry, 25(11), 3184–3188. target="_blank" rel="noopener"https://doi.org/10.1021/bi00359a016 Jariashvili, K., Madhan, B., Brodsky, B., Kuchava, A., Namicheishvili, L., & Metreveli, N. (2012). UV damage of collagen: insights from model collagen peptides. Biopolymers, 97(3), 189–198. https://doi.org/10.1002/bip.21725 Lee, Y. I., Lee, S. G., Jung, I., Suk, J., Lee, M. H., Kim, D. U., & Lee, J. H. (2022). Effect of a Collagen Tripeptide on Antiaging and Inhibition of Glycation of the Skin: A Pilot Study. International journal of molecular sciences, 23(3), 1101. https://doi.org/10.3390/ijms23031101 Hatanaka, T., Kawakami, K., & Uraji, M. (2014). Inhibitory effect of collagen-derived tripeptides on dipeptidylpeptidase-IV activity. Journal of enzyme inhibition and medicinal chemistry, 29(6), 823–828. https://doi.org/10.3109/14756366.2013.858143 Trzaskalski, N. A., Fadzeyeva, E., & Mulvihill, E. E. (2020). Dipeptidyl Peptidase-4 at the Interface Between Inflammation and Metabolism. Clinical medicine insights. Endocrinology and diabetes, 13, 1179551420912972. https://doi.org/10.1177/1179551420912972 Kieffer, T. J., McIntosh, C. H., & Pederson, R. A. (1995). Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology, 136(8), 3585–3596. https://doi.org/10.1210/endo.136.8.7628397 Kasina, S. V. S. K., & Baradhi, K. M. (2022). Dipeptidyl Peptidase IV (DPP IV) Inhibitors. In StatPearls. StatPearls Publishing. Asselin, J., Knight, C. G., Farndale, R. W., Barnes, M. J., & Watson, S. P. (1999). Monomeric (glycine-proline-hydroxyproline)10 repeat sequence is a partial agonist of the platelet collagen receptor glycoprotein VI. The Biochemical journal, 339 ( Pt 2)(Pt 2), 413–418. 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.
Pal-AHK (200mg)
Pal-AHK is a synthetic peptide composed of amino acids alanine, histidine, and lysine, with the addition of a palmitoyl group. Studies have only investigated the action of non-palmitoylated AHK. Still, Pal-AHK likely exerts similar impacts since adding palmitoyl to the AHK molecule is not likely to significantly alter the compound's mechanism of action. Palmitoylation is typically considered only to enhance a compound’s capacity for cell penetration, which may make it more capable of exerting action. Research suggests one key potential action of AHK and Pal-AHK may be to stimulate the production of collagen and elastin, two proteins considered essential within the extracellular matrix (ECM) of skin cells. Collagen is a major structural protein that lends strength and durability to the skin barrier, while elastin is considered responsible for supporting its elasticity. In addition to its potential for collagen and elastin production, Pal-AHK may also exhibit anti-oxidative action. Oxidative stress is considered to cause quantitative damage to cells and tissues. Antioxidants may help to neutralize free radicals, the main cause of oxidative stress. By scavenging these free radicals, antioxidants may prevent or reduce damage and environmental exposure biomarkers, including limiting wrinkle depth and length along the skin barrier. Studies have suggested that Pal-AHK may also have the potential to induce hair follicle growth due to anti-oxidative action and interaction with various molecules and growth factors. Examples include transforming growth factor-β1 (TGF-β1), Bcl-2/Bax ratio, vascular endothelial growth factor (VEGF), caspase-3, poly-(ADP-ribose) polymerase (PARP), and others. Chemical Makeup Molecular formula: C31H56N6O5 Molecular weight: 592.8 g/mol Other Known Titles: Palmitoyl AHK Research and Clinical Studies Pal-AHK Peptide and Antioxidation Tripeptide AHK was first developed from albumin hydrolysate.(2)(3) The addition of palmitoyl may improve the skin cell permeability of the peptide. Scientists report that the tripeptide may potentially reduce the expression of TGF-β1.(3) TGF-β1 is a molecule that supports the formation of new blood vessels and is considered to stimulate the production of extracellular matrix components, regulating the inflammatory response. Excessive activity may lead to chronic inflammation and tissue damage in certain contexts. Thus, reducing TGF-β1 levels may help to mitigate this action. The potential antioxidant action of Pal-AHK may be attributable to its unique amino acid composition.(4) Researchers suggest that the peptide “provides an increased dermal cell multiplication and viability to help to the production of collagen.” Researchers posit that this supposed action of AHK may directly impact the ECM through cell and protein production. Pal-AHK Peptide and Hair No research exists on Pal-AHK's impact on hair/fur growth. However, derivatives of AHK suggest that similarly structured compounds may promote the growth of hair follicles via the proliferation of dermal papilla cells (DPCs) and blocking their apoptosis.(5) The researchers suggested that AHK-analogs “stimulated the elongation of [...] hair follicles [...] and the proliferation of DPCs.” Pal-AHK may achieve similar potential by elevating the Bcl-2/Bax ratio and reducing negative growth factors such as cleaved caspase-3 and PARP. The Bcl-2/Bax ratio is considered important in regulating apoptosis (programmed cell death). Bcl-2 is classified an anti-apoptotic protein that may inhibit cell death, while Bax is a pro-apoptotic protein that may promote cell death. Thus, a higher Bcl-2/Bax ratio would indicate a predominance of Bcl-2, which may inhibit apoptosis and promote cell survival. The theoretical potential of Pal-AHK to promote hair growth by preventing dermal papilla cell apoptosis is a hypothesis founded on research that suggests the peptide’s involvement in reducing the levels of the cleaved forms of caspase-3 and PARP. Caspase-3 is considered to be a primary player in the process of apoptosis and is believed to contribute to the loss of dermal papilla cells when present in its cleaved, active form. When cleaved by caspase-3, PARP may facilitate cellular disassembly, a hallmark of apoptosis. Thus, inhibiting caspase-3 activation and reducing the cleaved forms of PARP as part of the same apoptotic pathway may plausibly contribute to decreased cell death in the hair follicles, potentially fostering an environment more conducive to hair retention and growth. Research also suggests this action possibly lowered apoptosis levels in these cell types under experimental observation.(6) Furthermore, studies report that Pal-AHK may increase the expression of vascular endothelial growth factor (VEGF), which, combined with reducing TGF-β1, may also help reduce shedding and promote hair growth.(7) VEGF is a protein that is considered to play an important role in angiogenesis. It is also thought to promote the growth of blood vessels around hair follicles, which may help supply nutrients and oxygen to the hair follicle and support growth. Pal-AHK Peptide and Skin Cells Although blocking TGF-β1 tends to have antiproliferative action, researchers suggest that Pal-AHK may stimulate the proliferation of skin cells and collagen synthesis via other pathways. The specific potential of Pal-AHK on the skin is yet to be investigated. Still, researchers have suggested that the main molecule, AHK, may yield positive action in preliminary laboratory research. One such potential is the viability and proliferation of dermal fibroblasts, key cells responsible for producing the essential proteins of the ECM, including collagen. Cell culture studies using normal dermal fibroblasts found that AHK appeared to increase cell growth and viability while potentially promoting the production of collagen type I.(8) This was determined by isolating the amount of collagen type I produced by fibroblasts in cell culture after incubation with various amounts of AHK. Results suggested that AHK may increase collagen type I production, with studies reporting a 300% increase compared to a control group. The findings suggest that AHK may potentially renew the extracellular matrix. Pal-AHK peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Tsuge, N., Eikawa, Y., Nomura, Y., Yamamoto, M., & Sugisawa, K. (1991). The anti-oxidative activity of peptides prepared by enzymatic hydrolysis of egg-white albumin. Journal of the Agricultural Chemical Society of Japan. Shimura, H., Tanaka, R., Shimada, Y., Yamashiro, K., Hattori, N., & Urabe, T. (2017). Glycyl-alanyl-histidine protects PC12 cells against hydrogen peroxide toxicity. BMC biochemistry, 18(1), 14. https://doi.org/10.1186/s12858-017-0089-x Nirmal, B. (2018). Key MessAges. IADVL Textbook of Trichology, 163. Kecel-Gunduza, S., Kocb, E., Bicaka, B., Kokcub, Y., Ozela, A. E., & Akyuzc, S. (2020). IN SILICO ANALYSIS FOR CHARACTERIZING THE STRUCTURE AND BINDING PROPERTIES OF ALA-HIS-LYS (AHK) TRIPEPTIDE. The Online Journal of Science and Technology-July, 10(3). Pyo, H. K., Yoo, H. G., Won, C. H., Lee, S. H., Kang, Y. J., Eun, H. C., Cho, K. H., & Kim, K. H. (2007). The effect of tripeptide-copper complex on human hair growth in vitro. Archives of pharmacal research, 30(7), 834–839. https://doi.org/10.1007/BF02978833 Anastassakis, K. (2022). Copper Tripeptides Copper tripeptides. In Androgenetic Alopecia From A to Z: Vol. 2 Drugs, Herbs, Nutrition and Supplements (pp. 225-230). Cham: Springer International Publishing. Sadgrove, N. J., & Simmonds, M. S. J. (2021). Nutricosmetic products for healthy hair and dermal antiaging using “dual-acting” (2 for 1) plant-based peptides, hormones, and cannabinoids. FASEB bioAdvances, 3(8), 601–610. https://doi.org/10.1096/fba.2021-00022 Patt, L. M., & Procyte, A. (2009). Neova® DNA Repair Factor Nourishing Lotion Stimulates Collagen and Speeds Natural Repair Process. skin, 1, 2. Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Oxytocin (10mg)
Oxytocin is a naturally occurring cyclic peptide hormone composed of nine amino acids. Scientists consider the peptide hormone to be secreted by the pituitary gland and to act as a neurotransmitter within the brain.(1) The synthetic form of the peptide, Recombinant Oxytocin, is a cyclic nonapeptide developed to be analogous to the naturally occurring peptide.(2) The first isolation of the peptide was carried out in 1920, followed by its structure discovery in the 1950s. Several research studies were conducted to fully explore the peptide's action and characteristics. Scientists consider it to be created by the hypothalamus, and Oxytocin is then secreted and stored in the posterior pituitary gland, potentially released in the event of a specific stimulation.(3) Unlike other hormones, naturally occurring Oxytocin has been posited to work via a positive feedback mechanism. This means that the initial secretion of the hormone peptide may lead to further release of the peptide in higher concentrations and with higher intensity.(3) Both synthetic and natural forms appear to work through the same potential mechanisms. Considered to be especially pivotal in the process of gestation and labor, Oxytocin, once secreted into the system, may bind with the G-protein coupled receptors to potentially increase intracellular calcium levels. This calcium secretion may have various downstream impacts, such as inducing uterine contractions. Once the uterine contractions begin, they may stimulate further release of Oxytocin, leading to higher frequency and intensity of the contractions via a positive feedback mechanism.(3) The peptide appears to contribute to the contractions of myoepithelial cells found in the alveolar ducts of mammary glands. These contractions may stimulate milk ejection from alveolar ducts into the larger sinuses, thereby expelling milk. The positive feedback mechanism may also work here, with initial milk expulsion potentially stimulating increased Oxytocin circulation and continuous milk release.(3) Chemical Makeup Molecular Formula: C43H66N12O12S2 Molecular Weight: 1007.193 g/mol Other Known Titles: endopituitrina Research and Clinical Studies Oxytocin Peptide and Dopamine Signaling Oxytocin might play a role in shaping sexual behavior by possibly influencing the activity of dopamine within central nervous system regions associated with the rewards system, notably the ventral tegmental area (VTA) and the nucleus accumbens.(4) This influence may stem from projections of Oxytocin to the VTA, where the peptide may either augment dopamine release, or enhance the sensitivity of dopaminergic neurons. Such an increase in dopaminergic activity may, in turn, potentially boost sexual motivation and the perception of reward, possibly aiding the anticipatory aspects of mating and copulatory behavior. The hypothesis suggests that Oxytocin may directly interact with dopaminergic neurons within the VTA by activating specific oxytocin receptors, initiating a sequence of events that culminates in heightened dopamine release within the nucleus accumbens. This sequence may include the stimulation of nitric oxide synthesis within the VTA, hinting at an intricate interplay involving Oxytocin, dopamine, and nitric oxide. Additionally, there is the potential for Oxytocin to exert an indirect action on dopaminergic activity across other cerebral locales, including the hippocampus and amygdala, adding further depth to its complex role. Such indirect influences might modulate the activity of either glutamatergic or GABAergic neurons, which may, in turn, influence dopaminergic neurons located within the VTA and nucleus accumbens.(4) Oxytocin Peptide and Neuroplasticity Researchers are actively exploring Oxytocin's impact on developing or maintaining neuroplasticity. The peptide is posited to engage with G-protein coupled receptors, which may increase intracellular calcium levels.(5) This elevation in calcium is thought to play a role in neuronal excitability and synaptic modulation, affecting the transmission of signals across neurons. Oxytocin's potential influence in the brain may extend to neurogenesis and synaptic plasticity, which may impact the intricate dance of neural circuit formation and function. The presence of Oxytocin receptors across various neural cell types hints at the peptide's broad potential impact, possibly modulating the behavior of neural progenitor cells and influencing the fate of these cells. This action might stretch into early brain development, where Oxytocin's presence might subtly shape the emerging neural circuits by modulating neurotransmitter dynamics, including those of glutamate and GABA, which serve as the brain's primary excitatory and inhibitory signals, respectively. At the synaptic level, Oxytocin's actions appear to diverge, potentially enhancing neurotransmitter release in some contexts, while diminishing it in others. This dual action may reflect Oxytocin's potential to modulate the balance between excitation and inhibition within the neural circuits, a balance considered crucial for maintaining the functional integrity of the brain. Such modulation may manifest through alterations in the release of neurotransmitters or changes in membranes, indirectly influencing neuronal excitability and the flow of neural information. The interactions of Oxytocin with glial cells, such as astrocytes, further complicate its role in neurotransmitter dynamics, suggesting a broader regulatory influence that extends beyond the neurons to the supportive environment that nurtures and maintains synaptic connections. This interaction may influence the synaptic plasticity and overall function of neural circuits, offering a glimpse into the complex regulatory roles Oxytocin might play in the neural ecosystem.(5) Oxytocin Peptide and Labor Induction The main aim of this clinical study(6) was to determine the rate of cesarean delivery in pregnant females after removing Oxytocin presence once active labor starts (5 cm cervical dilation) compared to pregnant females where Oxytocin was given until the maintenance level as determined in clinical trial study protocol. A randomized study was conducted on 252 female subjects between 18 to 50 years. The subjects were divided into two groups, with 127 subjects (Group A) continuously given the peptide per study protocol even after the subjects reached active labor, and 125 subjects (Group B) given Oxytocin, discontinued after active labor induction. After a 24-72 hour study period, there were 32 reported cesarean deliveries in Group A, with 10 infants exhibiting one or more abnormalities that warranted further observation. In contrast, there were 24 reported cesarean deliveries in Group B, with 9 infants exhibiting abnormalities. Oxytocin Peptide and Lactation The main goal of this clinical study(7) was to evaluate the potential action of peptide supplementation during the course of breastfeeding. A retrospective study(7) was conducted where 100 pregnant females given Oxytocin during labor were compared with 100 pregnant females not exposed to Oxytocin. Following the study result analysis, the researchers reported that the new mothers exposed to Oxytocin exhibited apparently impaired breastfeeding for the first hour. During the first three months after delivery, subjects from both groups (27% exposed to Oxytocin and 14% without) were not apparently able to breastfeed. Following three months, breastfeeding was reported to significantly increase in the Oxytocin-exposed subjects. The reason suggested by researchers for impaired breastfeeding during the first three months was the high pre-gestational body mass index in the test subjects. Oxytocin Peptide and Vasodilation Vasodilation is the dilation of blood vessels, which is considered to be a mechanism to increase blood flow. The main purpose of this study(8) was to evaluate the potential of Oxytocin on cardiac function and tone in the heart muscles. The study observed a set of pregnant females in the first trimester, divided into two groups, one given Oxytocin and the other a placebo. Heart rate and blood pressure were recorded. The results suggested that the peptide may have exhibited vasodilatory properties on the small and outlying arteries and elevated left ventricular ejection time. Oxytocin Peptide and Autism The main aim of this clinical study(9) was to evaluate what action, if any, the peptide may exert on research models of autism. Autism is considered to be a psychiatric disorder related to poor brain development impacting how the subject socializes and communicates. A total of 59 autistic males, aged 6 to 11 years, were examined in this study. Out of the 59 test subjects, 29 were autistic, and the rest were considered control subjects by the researchers. The plasma levels of Oxytocin were measured in this study, and the researchers reported that autistic subjects exhibited lower levels of peptide hormone than the control subjects. Once the levels of Oxytocin were elevated as part of the study, the VABS score (analytic behavior score) of autistic subjects appeared to improve. Oxytocin peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: National Center for Biotechnology Information. "PubChem Compound Summary for CID 439302, Oxytocin" PubChem Recombinant Oxytocin (Code C724). https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C724 Osilla EV, Sharma S. Oxytocin. [Updated 2021 Jul 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. https://www.ncbi.nlm.nih.gov/books/NBK507848/ Melis, Maria Rosaria, and Antonio Argiolas. “Oxytocin, Erectile Function and Sexual Behavior: Last Discoveries and Possible Advances.” International journal of molecular sciences vol. 22,19 10376. 26 Sep. 2021, doi:10.3390/ijms221910376 Bakos, Jan et al. “Molecular Mechanisms of Oxytocin Signaling at the Synaptic Connection.” Neural plasticity vol. 2018 4864107. 2 Jul. 2018, doi:10.1155/2018/4864107 Diven, Liany C et al. “Oxytocin discontinuation during active labor in women who undergo labor induction.” American journal of obstetrics and gynecology vol. 207,6 (2012): 471.e1-8. doi:10.1016/j.ajog.2012.08.035 Gomes M, Trocado V, Carlos-Alves M, Arteiro D, Pinheiro P. Intrapartum synthetic oxytocin and breastfeeding: a retrospective cohort study. J Obstet Gynaecol. 2018 Aug;38(6):745-749. Epub 2018 Mar 9. https://pubmed.ncbi.nlm.nih.gov/29523035/ Rabow, S., Hjorth, U., Schönbeck, S. et al. Effects of oxytocin and anaesthesia on vascular tone in pregnant women: a randomized, double-blind placebo-controlled study using non-invasive pulse wave analysis. BMC Pregnancy Childbirth 18, 453 (2018). Cochran, D. M., Fallon, D., Hill, M., & Frazier, J. A. (2013). The role of oxytocin in psychiatric disorders: a review of biological and therapeutic research findings. Harvard review of psychiatry, 21(5), 219–247. https://doi.org/10.1097/HRP.0b013e3182a75b7d Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
Sermorelin & GHRP-6 & GHRP-2 Blend (9mg)
Blending the peptides Sermorelin, GHRP-2, and GHRP-6 may be practical for researchers aiming to investigate the potential of stimulating pituitary cells (somatotrophs) via multiple pathways. Specifically, these three peptides appear to interact with pituitary cells via different receptors. Sermorelin is a research peptide made of 29 amino acids that is a shortened version of the endogenous 44 amino acid structure of Growth Hormone-Releasing Hormone (GHRH). Similar to its endogenous counterpart, Sermorelin appears to interact with the cells via the GHRH-receptor, which is also considered the main receptor for stimulating growth hormone (hGH) release from the pituitary cells. GHRP-2 and GHRP-6 are fully synthetic peptides that are posited as growth hormone secretagogues (GHSs) as they appear to interact with another set of receptors on the somatotrophs. Specifically, those are the growth hormone secretagogue receptors type 1a (GHS-R1a), which also respond to the hormone ghrelin. Despite sharing no homology with ghrelin, GHRP-2 and GHRP-6 appear to reliably activate the GHS-R1a and also stimulate hGH release from the pituitary cells. Several experiments suggest that simultaneously activating the GHS-R1a and GHRH receptors may produce combined and synergistic actions. Chemical Makeup Other Known Titles Sermorelin: GRF 1-29 NH2 GHRP-2: pralmorelin GHRP-6: SKF-110679, growth hormone-releasing hexapeptide Molecular Weight: Sermorelin: 93 g/mol GHRP-2: 97 g/mol GHRP-6: 03 g/mol Molecular Formula: Sermorelin: C149H246N44O42S GHRP-2: C45H55N9O6 GHRP-6: C46H56N12O6 Research and Clinical Studies Sermorelin & GHRP-2 & GHRP-6 Receptor Interactions According to research by Clark et al., Sermorelin appears to interact with the GHRH receptors.(1) This is allowed by its structure as it is the shortest functional analog of endogenous GHRH with a C-terminal amidation that may help stabilize the molecule. According to studies by Culhane et al., it appears to activate the GHRH receptors through several steps, which may involve the activation of an intracellular messenger called cyclic AMP (cAMP) and the kinase PKA (protein kinase A), which together may switch on the cellular machinery that synthesizes and releases hGH.(2) There does not appear to be desensitization according to the available laboratory research. The resulting hGH synthesis may have direct and indirect actions. The indirect may be via its anabolic mediator IGF-1 (insulin-like growth factor-1), which is produced in other tissue cells when they are presented with hGH. GHRP-2 and GHRP-6 appear to interact with the GHS-R1a, also referred to as the ghrelin receptors. However, these two hexapeptides have no similarities with ghrelin in terms of structure, as highlighted by the work of Bowers et al in 2012.(3) Furthermore, laboratory research by Yin et al. suggests that they may exert a chain of intracellular cascades and events in somatotrophs by interacting with these receptors. Researchers posit that GHRP-2 and GHRP-6 may activate the receptors by interacting with the enzyme phospholipase C (PLC), which cuts a specific membrane molecule (PIP₂) into two smaller signaling molecules called IP₃ and DAG. The latter may help switch on another enzyme family called protein kinase C (PKC), which is posited to interact with protein synthesis related to hGH synthesis. On the other hand, IP₃ appears to interact with the internal calcium stores of pituitary cells, causing Ca²⁺ to be released into the cytoplasm, which may then release hGH molecules out of the pituitary cells. Sermorelin & GHRP-2 & GHRP-6 and hGH Synthesis Laboratory work in pituitary cell models suggests that exposing somatotrophs to Sermorelin may upregulate hGH synthesis, although the specific action size varies between studies. For example, in an experiment reported by Vittone et al., the mean 12-hour growth hormone concentrations were described as rising about 2-fold from about 1.1 ± 0.9 µg/L to roughly 2.2 ± 1.9 µg/L.(5) The cumulative hGH output for these 12 hours also appeared to increase 2-fold, from around 1,114 ± 931 to about 2,032 ± 1,728 µg·min/L. Additional work by Khorram et al. suggests that the increase may particularly occur during the first 2 hours of exposure, while longer windows may blend early peaks with later, lower-amplitude release.(6) They employed a slightly modified Sermorelin molecule. They described that the 2-hour integrated growth hormone signal appeared to shift from roughly 200–300 to about 1,100–1,600 µg·L⁻¹·min, which is close to a sixfold rise. GHRP-2 and GHRP-6 also appear to induce short-term peaks in hGH levels. For example, older research by Bowers et al. from 2004 suggests that under continuous 24-hour evaluation, GHRP-2 may also increase growth hormone production from approximately 20–30 µg·L⁻¹·24 h in placebo controls to about 120–180 µg·L⁻¹·24 h with GHRP-2, suggesting an estimated 4- to 6-fold increase. On the other hand, research by Micic et al. investigated peak growth hormone responses of pituitary cells after stimulation with GHRP-6 and reportedly observed a rise from basal 1–2 mU/L to around 60 mU/L.(8) Based on this data, the peptide may induce peaks that exceed 3-fold the typical physiological peaks that may reach about 20 mU/L. Indeed, the researchers also commented that “GH responses to GHRP-6 are much greater than to GHRH”. Sermorelin & GHRP-2 & GHRP-6 and Anabolic Signaling Based on the aforementioned publications by Khorram et al. and the research by Bowers et al., from 2004 suggest that the peptides may induce a significant stimulation of hGH synthesis in pituitary cells that may then prove to be sufficient to induce IGF-1 synthesis in nearby cell cultures.(6)(7) More specifically, Khorram et al. suggested that there has been about a 27–28% increase in IGF-1 synthesis following Sermorelin experimentation. With the GHRP-2 exposure for 24 hours, Bowers et al. suggested that the IGF-1 levels may have increased from 90–100 µg/L to approximately 150–160 µg/L, which is equal to roughly a 50–80% increase. Unfortunately, the GHRP-6 experiment by Micic et al. was too short to report any data on IGF-1 synthesis.(8) Sermorelin & GHRP-2 & GHRP-6 and Synergistic Actions Blending Sermorelin with GHRP-2 and GHRP-6 is often framed as a practical way to evaluate dual-receptor stimulation in somatotroph systems. When both receptor families are activated at the same time, several experimental datasets suggest that growth hormone output may rise beyond what is seen with either pathway alone, which is compatible with additive or synergistic coupling at the level of pituitary signaling. Unfortunately, most of the experiments have evaluated GHRP-2 or GHRP-6 with full-length GHRH rather than Sermorelin, but such results are valuable for future research. For example, the pituitary models described by Micic et al. reveal that GHRP-6 alone was associated with a peak growth hormone response around 60 mU/L, while the combination of GHRP-6 with full-length GHRH was reported to raise the peak to roughly 140 mU/L, or 7-fold higher than the highest physiological peaks.(8) Cordido et al. also suggested that GHRP-6 alone produced an average peak around 6 mU/L, while the GHRH analogue alone produced a smaller peak near 2.6 mU/L. When both secretagogues were applied together, the peak rose to about 16.3 mU/L. Their integrated 12-hour data followed the same direction. The reported 12-hour growth hormone exposure was around 260 mU·min/L with GHRP-6 alone and about 159 mU·min/L with the GHRH analogue alone, but increased to roughly 729 mU·min/L when the two were combined.(9) Comparable synergy signals have been reported for GHRP-2 when combined with endogenous, full-length GHRH in experimental pituitary systems. In the work by Veldhuis et al., each peptide produced a large outcome on its own. However, the combination still yielded an extra increment. (10) In their models, GHRH alone was estimated to raise growth hormone burst output by roughly 20-fold over baseline. At the same time, GHRP-2 alone was associated with an even larger rise, around 47-fold. When both stimuli were present, the calculated response increased to about 54-fold above saline, which corresponds to a modest additional gain over GHRP-2 alone. The aforementioned 2004 research on GHRP-2 by Bowers et al. also included GHRH co-evaluation and concluded that the “combined GHRP-2 and GHRH drive is more effective than either agonist alone.”” Currently, only the research by Sigalos et al. evaluated a combination of Sermorelin with both GHRP-2 and GHRP-6.(11) Their findings suggest an upward shift in IGF-1 from baseline values around 160 ng/mL to roughly 250–265 ng/mL, which corresponds to an apparent 1.6-fold increase. Because the design involved multiple peptides and did not isolate each contribution, the data do not map cleanly onto a single receptor-pair interaction. Still, the direction of change is compatible with the broader observation that GHRH-receptor input and GHS-R1a input may cooperate to increase downstream hGH output. Sermorelin & GHRP-2 & GHRP-6 blend is available for research and laboratory purposes only. Please review our Terms and Conditions before ordering. References: Clark RG, Robinson IC. Growth induced by pulsatile infusion of an amidated fragment of hGH-releasing factor in normal and GHRF-deficient rats. Nature. 1985 Mar 21-27;314(6008):281-3. doi: 10.1038/314281a0. PMID: 2858818. Culhane KJ, Liu Y, Cai Y, Yan EC. Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors. Front Pharmacol. 2015 Nov 5;6:264. doi: 10.3389/fphar.2015.00264. PMID: 26594176; PMCID: PMC4633518. Bowers CY. History of the discovery of ghrelin. Methods Enzymol. 2012;514:3-32. PMID: 22975043. https://doi.org/10.1016/B978-0-12-381272-8.00001-5 Yin Y, Li Y, Zhang W. The growth hormone secretagogue receptor: its intracellular signaling and regulation. Int J Mol Sci. 2014 Mar 19;15(3):4837-55. doi: 10.3390/ijms15034837. PMID: 24651458; PMCID: PMC3975427. Vittone J, Blackman MR, Busby-Whitehead J, Tsiao C, Stewart KJ, Tobin J, Stevens T, Bellantoni MF, Rogers MA, Baumann G, Roth J, Harman SM, Spencer RG. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. 1997 Jan;46(1):89-96. doi: 10.1016/s0026-0495(97)90174-8. PMID: 9005976. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997 May;82(5):1472-9. doi: 10.1210/jcem.82.5.3943. PMID: 9141536. Bowers, C. Y., Granda, R., Mohan, S., Kuipers, J., Baylink, D., & Veldhuis, J. D. (2004). Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women. The Journal of clinical endocrinology and metabolism, 89(5), 2290–2300. https://doi.org/10.1210/jc.2003-031799 Micic D, Popovic V, Kendereski A, Macut D, Casanueva FF, Dieguez C. Growth hormone secretion after the administration of GHRP-6 or GHRH combined with GHRP-6 does not decline in late adulthood. Clin Endocrinol (Oxf). 1995 Feb;42(2):191-4. doi: 10.1111/j.1365-2265.1995.tb01861.x. PMID: 7734029. Cordido F, Peñalva A, Dieguez C, Casanueva FF. Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity. J Clin Endocrinol Metab. 1993 Apr;76(4):819-23. doi: 10.1210/jcem.76.4.8473389. PMID: 8473389. Veldhuis JD, Keenan DM. Secretagogues govern GH secretory-burst waveform and mass in healthy eugonadal and short-term hypogonadal men. Eur J Endocrinol. 2008 Nov;159(5):547-54. doi: 10.1530/EJE-08-0414. Epub 2008 Aug 14. Erratum in: Eur J Endocrinol. 2008 Dec;159(6):841. PMID: 18703567; PMCID: PMC2680123. Sigalos JT, Pastuszak AW, Allison A, Ohlander SJ, Herati A, Lindgren MC, Lipshultz LI. Growth Hormone Secretagogue Treatment in Hypogonadal Men Raises Serum Insulin-Like Growth Factor-1 Levels. Am J Mens Health. 2017 Nov;11(6):1752-1757. doi: 10.1177/1557988317718662. Epub 2017 Aug 22. PMID: 28830317; PMCID: PMC5675260. 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.
Decapeptide-12 (200mg)
Decapeptide-12 is a synthetic peptide that is composed of 10 amino acids. Its developers and subsequent researchers have suggested that Decapeptide-12 may potentially inhibit melanin production in the skin by suppressing the activity of tyrosinase, an enzyme involved in the synthesis of melanin. Decapeptide-12 does not appear to mimic any naturally occurring peptide. Rather, it was designed and synthesized to exhibit specific properties. Decapeptide-12 is primarily researched in reducing melanin production and hyperpigmentation. It has also been studied for its potential impact on cell growth, differentiation, and mitigating cell aging. However, more research is needed to fully understand the potential properties and results of Decapeptide-12 experiments in these contexts. Chemical Makeup Molecular Formula: C65H90N18O17 Molecular Weight: 1311.46 g/mol Overview and Mechanisms of Action As mentioned, Decapeptide-12 is posited to work primarily by inhibiting melanin synthesis, aka melanogenesis. Melanin synthesis is suggested to be a complex biochemical pathway that may occur within specialized cells in the skin called melanocytes. Tyrosinase is posited to play a pivotal role in this pathway as it appears to catalyze the first two steps in melanin production: the hydroxylation of tyrosine to DOPA (3,4-dihydroxyphenylalanine) and the oxidation of DOPA to DOPAquinone. These reactions are suggested to be essential for the subsequent production of eumelanin and pheomelanin, the two main types of melanin pigments that determine skin, hair, and eye color and may protect against UV radiation. As mentioned, Decapeptide-12 may act by potentially inhibiting tyrosinase activity. While the precise molecular mechanisms are complex and involve multiple pathways, the basic understanding is that Decapeptide-12 may bind to specific sites on the tyrosinase enzyme or its mRNA, thereby blocking the enzyme's ability to catalyze the aforementioned critical reactions in melanin synthesis. This inhibition could occur through direct interaction with the enzyme, leading to a change in its conformation and reducing its catalytic efficiency. Alternatively, Decapeptide-12 might interfere with the enzyme's gene expression, lowering the amount of functional tyrosinase produced in the melanocytes. Research and Clinical Studies Decapeptide-12 and Melasma One clinical study aimed to evaluate the potential of Decapeptide-12 in test subjects with moderate to severe melasma, solar lentigines, periocular lines, and wrinkles.(1) This 24-week experiment reported apparent improvements in all of the reported facial conditions among the 25 subjects, with sustained impact. Another clinical trial investigated the potential of Decapeptide-12 on mild-to-moderate melasma in 33 test subjects over 16 weeks.(2) Results suggested a visible reduction in the appearance of melasma. Furthermore, one study reported a complete clearance of melasma in 25% of subjects after six weeks of Decapeptide-12 presentation.(3) Decapeptide-12 also was reported by the researchers to exhibit an apparent impact in test subjects with the Fitzpatrick phototype IV skin type and moderate recalcitrant melasma completed.(4) Subjects with Fitzpatrick skin type IV are reportedly some of the most common melasma sufferers. The researchers concluded that: “All […] demonstrated statistically significant improvement in the appearance of melasma and overall facial aesthetics.” Decapeptide-12 and Post-inflammatory Hyperpigmentation A clinical case study on pigmented skin (Fitzpatrick skin type IV) indicated that Decapeptide-12 may possibly accelerate the clearance of post-inflammatory hyperpigmentation compared to placebo.(5) The researchers suggest this might be due to the tyrosinase-inhibiting potential of Decapeptide-12.(6) Decapeptide-12 and Solar Lentigo One study evaluated the impact of Decapeptide-12 in the form of hyperpigmentation called solar lentigines caused by chronic photodamage.(7) The results reported that 38.5% of the models evaluated appeared to have achieved complete clearance, and all subjects appeared to exhibit some improvement. Furthermore, 30.7% of the models were reported to improve from a moderate degree of photodamage to a milder degree, 15.4% improved from a severe degree to a moderate degree, and another 15.4% improved from a severe degree to a milder degree after 24 weeks. Decapeptide-12 and Cell Aging Sirtuins are a family of genes involved in various cellular processes. They are believed to regulate cellular metabolism, DNA repair, inflammation, and stress resistance. One of the most well-known sirtuins is SIRT1, which has been suggested to regulate various biological pathways, such as glucose metabolism, lipid metabolism, and cellular stress responses. Studies have also suggested that SIRT1 may be involved in extending the lifespan in certain model organisms. One of the most promising compounds is resveratrol, found in red wine, and has been suggested to activate SIRT1 in some studies. One study looked at the potential of Decapeptide-12 on sirtuin gene expression levels in keratinocyte progenitors.(8) The researchers used RT-PCR to measure the impact of Decapeptide-12 on seven Sirtuin genes and cellular viability and proliferation after 72-hour incubation with various concentrations of Decapeptide-12. The results suggested that Decapeptide-12 possibly increased the transcription of several Sirtuin genes, including SIRT1, SIRT3, SIRT6, and SIRT7, with reportedly reduced cytotoxicity. The researchers reported that “ decapeptide-12 increased transcription of SIRT1 by 141 ± 11% relative to control cells, whereas levels of SIRT3, SIRT6, and SIRT7 were increased by 121 ± 13%, 147 ± 8% and 95± 14%, respectively.” SIRT1, with a reported increase in transcription by 141 ± 11% may enhance cellular resilience against oxidative stress and inflammation, possibly delaying aging processes on a cellular level. The apparent increases in SIRT3 (121 ± 13%) and SIRT6 (147 ± 8%) transcription levels further amplify the possible research outcomes. SIRT3's potential involvement in mitochondrial function and energy metabolism suggests that decapeptide-12 might enhance mitochondrial efficiency and antioxidant capacity. Similarly, SIRT6 is possibly associated with DNA repair, telomere maintenance, and inflammation regulation. Its potential upregulation might contribute to improved genomic stability and reduced inflammation, potentially further decelerating the aging process in cells. While the reported increase in SIRT7 transcription (95 ± 14%) appears less pronounced, it may still indicate potential influence on nucleolar functions, including ribosome biogenesis and stress sensing. This subtle modulation might also contribute to the overall cellular homeostasis and longevity.(8) Decapeptide-12 is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Jiang, L., Hino, P. D., Bhatia, A., Stephens, T. J., & Jimenez, F. (2018). Efficacy of Trifecting® Night Cream, a Novel Triple acting Skin Brightening Product: A Double-blind, Placebo-controlled Clinical Study. The Journal of clinical and aesthetic dermatology, 11(12), 21–25. Ramírez, S. P., Carvajal, A. C., Salazar, J. C., Arroyave, G., Flórez, A. M., & Echeverry, H. F. (2013). Open-label evaluation of a novel skin brightening system containing 0.01% decapeptide-12 in combination with 20% buffered glycolic acid for the treatment of mild to moderate facial melasma. Journal of drugs in dermatology : JDD, 12(6), e106–e110. Hantash, B. M., & Jimenez, F. (2012). Treatment of mild to moderate facial melasma with the Lumixyl brightening system. Journal of drugs in dermatology : JDD, 11(5), 660–662. Hantash, B. M., & Jimenez, F. (2009). A split-face, double-blind, randomized and placebo-controlled pilot evaluation of a novel oligopeptide for the treatment of recalcitrant melasma. Journal of drugs in dermatology : JDD, 8(8), 732–735. Bhatia, A., Hsu, J. T.s, & Hantash, B. M. (2014). Combined delivery and dermalinfusion of decapeptide-12 accelerates resolution of post-inflammatory hyperpigmentation in skin of color. Journal of drugs in dermatology : JDD, 13(1), 84–85. Chen, J., Bian, J., Hantash, B. M., Albakr, L., Hibbs, D. E., Xiang, X., Xie, P., Wu, C., & Kang, L. (2021). Enhanced skin retention and permeation of a novel peptide via structural modification, chemical enhancement, and microneedles. International journal of pharmaceutics, 606, 120868. https://doi.org/10.1016/j.ijpharm.2021.120868 Kassim, A. T., Hussain, M., & Goldberg, D. J. (2012). Open-label evaluation of the skin-brightening efficacy of a skin-brightening system using decapeptide-12. Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology, 14(2), 117–121. https://doi.org/10.3109/14764172.2012.672745 Basil, M. H., & Anan, A. U. (2019). Tyrosinase inhibitors with potent anti-senescence activity in human neonatal keratinocyte progenitors. J Dermatol Surg Res Ther, 2019, 30-39. 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.
Triptorelin (2mg)
Triptorelin is a synthetic peptide composed of ten amino acids, similar to gonadotropin-releasing hormones (GnRH).(1) GnRH, secreted by the hypothalamus, is considered by scientists to be responsible for the synthesis and secretion of the follicle-stimulating hormone (FSH) and luteinizing hormone (LH).(2) Triptorelin may act similarly on the pituitary gland to stimulate the synthesis and release of the LH and FSH hormones, both apparently vital for testosterone production in male species and estrogen synthesis in female species.(3) Overview As an agonist analog of GnRH, researchers have suggested that Triptorelin binds to the receptors in the pituitary gland, which may then stimulate the secretion of LH and FSH. This, at first, may cause an upsurge in the initial phase of LH and FSH stimulation. However, it is important to note that Triptorelin is an analog that appears to have upregulated stability and affinity to the receptors than endogenous GnRH. Thus, the receptors eventually may become less sensitive to the compound (i.e., downregulation of the receptors), and Triptorelin may lead to reduced release of LH and FSH. Scientists consider that a reduction in the levels of LH and FSH hormones eventually leads to a decrease in testosterone and estrogen levels. This event may lead to the suppression of steroidogenesis by ovaries and testicles.(4) Researchers suggest that Triptorelin exhibits some potential in sustaining the decline in LH and FSH secretion. Therefore, intermittent exposure to Triptorelin may upregulate hormonal levels, while prolonged exposure may lead to dramatic suppression. Chemical Makeup Molecular Formula: C64H82N18O13 Molecular Weight: 1311.4 g/mol Other Known Titles: 57773-63-4 Research and Clinical Studies Triptorelin Peptide and Hormonal Upregulation It is posited that a single exposure to Triptorelin may, under certain experimental conditions, potentially induce a surge in hormone release from cells by interacting with receptors that control gonadotropin secretion.(5) This single interaction may temporarily reset or stimulate the hypothalamic-pituitary axis, thereby possibly enhancing the secretion of endogenous gonadotropins and subsequent hormonal synthesis. It is hypothesized that Triptorelin might activate signaling pathways that had been previously suppressed or downregulated, possibly leading to an increase in luteinizing hormone release and ultimately fostering the synthesis of androgens. The signaling pathways may be suppressed due to previous exposure to androgenic anabolic agents, which may “have pronounced effects on the male pituitary-gonadal axis, affecting the regulation of production of serum luteinizing hormone (LH) and follicle-stimulating hormone and inducing a state of hypogonadotropic hypogonadism characterized by decreased serum endogenous testosterone production and impaired spermatogenesis”. Studies employing controlled conditions have suggested that even a one-time exposure could serve as a catalyst for restoring or augmenting endogenous hormone production. The underlying biological processes, however, remain complex and may depend on multiple variables that have yet to be fully elucidated. Triptorelin Peptide and Hormonal Suppression Prolonged exposure to triptorelin may, according to various mechanistic hypotheses, alter the normal function of GnRH receptors.(6) Instead of the typical pulsatile pattern that is possibly required to maintain receptor sensitivity, the continuous presence of a GnRH analog might potentially lead to a state of receptor desensitization. This desensitization, as posited by some researchers, may potentially be tied to alterations in receptor trafficking, where receptors may become internalized and apparently not recycled to the cell surface as efficiently. Such a process may diminish their ability to respond to further stimulation, thereby reducing the secretion of upstream hormones, and ultimately lowering the synthesis of downstream hormones. Studies employing controlled research approaches have hinted that this continuous stimulation may induce conformational changes in the receptor or associated signaling proteins. These changes may disrupt the receptor’s normal feedback and resensitization mechanisms. Over time, this condition could result in persistently dampened signaling cascades, potentially leading to less hormonal release and reduced hormone production at later stages in the endocrine pathway. Triptorelin Peptide and Thymus Cells In murine models, GnRH-analog peptides structurally related to Triptorelin have been posited to interact with specific binding sites within thymic compartments, potentially influencing immune-related processes.(7) It is possible that age-related reductions in LHRH-binding sites, coupled with complex endocrine-immune signaling pathways, obscure the precise manner in which Triptorelin might modulate thymic function. The researchers have commented that the peptide may “exert a powerful modulation of immune system function during the physiological decline of immunological capacities.” However, the limited data currently available may stem from the difficulty in separating local thymic actions from broader neuroendocrine influences, as well as from the challenges of elucidating how these peptides apparently alter receptor densities, cellular organization, and the proliferative capacity of T-lymphocyte precursors. Therefore, it remains uncertain how Triptorelin could potentially modulate immunity at the molecular and cellular level. Triptorelin peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: National Center for Biotechnology Information. PubChem Compound Summary for CID 25074470, Triptorelin. Tsutsumi, Rie, and Nicholas J G Webster. “GnRH pulsatility, the pituitary response and reproductive dysfunction.” Endocrine journal vol. 56,6 (2009): 729-37. doi:10.1507/endocrj.k09e-185. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307809/ LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Triptorelin. https://www.ncbi.nlm.nih.gov/books/NBK548756/ Lepor, Herbert. “Comparison of single-agent androgen suppression for advanced prostate cancer.” Reviews in urology vol. 7 Suppl 5 (2005): S3-S12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1477619/ Pirola I, Cappelli C, Delbarba A, Scalvini T, Agosti B, Assanelli D, Bonetti A, Castellano M. Anabolic steroids purchased on the Internet as a cause of prolonged hypogonadotropic hypogonadism. Fertil Steril. 2010 Nov;94(6):2331.e1-3. doi: 10.1016/j.fertnstert.2010.03.042. Epub 2010 Apr 22. PMID: 20416868. Chung LY, Kang E, Nam HK, Rhie YJ, Lee KH. Efficacy of Triptorelin 3-Month Depot Compared to 1-Month Depot for the Treatment of Korean Girls with Central Precocious Puberty in Single Tertiary Center. J Korean Med Sci. 2021 Aug 30;36(34):e219. doi: 10.3346/jkms.2021.36.e219. PMID: 34463062; PMCID: PMC8405405. Marchetti B, Guarcello V, Morale MC, Bartoloni G, Raiti F, Palumbo G Jr, Farinella Z, Cordaro S, Scapagnini U. Luteinizing hormone-releasing hormone (LHRH) agonist restoration of age-associated decline of thymus weight, thymic LHRH receptors, and thymocyte proliferative capacity. Endocrinology. 1989 Aug;125(2):1037-45. doi: 10.1210/endo-125-2-1037. PMID: 2546733. 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.
Thymosin Alpha-1 (5mg / 10mg)
Thymosin Alpha-1 peptide, also known as Thymosin Alpha, TA1, or T α 1, is a fragment of a protein molecule that has been widely studied for its potential implications with the immune system. Researchers have hypothesized that it contributes to the production of T-cells to mitigate and alleviate infection and bacterial spread.(1) Thymosin Alpha-1 is a naturally occurring polypeptide that is considered by researchers to potentially restore and enhance immune functions.(2) Thymosin Alpha-1 is considered to be one of the polypeptides found in Thymosin Fraction 5, which is a crude extract of the thymus gland.(3) Since its discovery, a synthetically developed form of Thymosin Alpha-1 has also been studied, researchers refer to the peptide as Thymalfasin.(2) Thymalfasin is composed of 28 amino acids, similar to the naturally occurring Tα 1, and is derived from a longer polypeptide precursor composed of 113 amino acids, known as Prothymosin Alpha.(3) Overview The main aim of initial research into Thymosin Alpha-1(4) was to understand and examine the immunomodulating potential of the peptide. Studies have suggested that the peptide may increase the concentration of the major histocompatibility complex (MHC) class I and cytokine production, which may possibly lead to increased immune responses. The peptide may also enhance the activity of natural killer cells and foster the expression of phenotypic markers on T cells, suggesting a multi-faceted role in modulating the immune response. The researchers posited that the peptide may also increase the expression of high-affinity receptors for interleukin-2. This could potentially lead to a more vigorous activation and proliferation of T lymphocytes. Researchers speculate that Thymosin Alpha-1 may stimulate possible action by targeting the T-helper cells and cytotoxic T-cell populations.(3) Tα 1 may possibly induce differentiation of the T-cells (thymocytes) and the terminal differentiation of the blood lymphocytes. Scientists posit that it may elevate the production of the natural killer cells and potentially stimulate cytokine mediated inflammation.(2)(3) Furthermore, the peptide has been studied for its potential to enhance efficiency of macrophages and functions as the modulator of the alpha thrombin activity.(3) Specifications Molecular Formula: C129H215N33O55 Molecular Weight: 3108.31 g/mol Other Known Titles: TA1, Tα1, Thymalfasin Research and Clinical Studies Thymosin Alpha-1 Peptide and Immune System In a clinical study,(5) 11 test subjects with different immune system dysfunctions were evaluated for the levels of their natural killer (NK) and lymphokine activated killer cells (LAK) present in their system. It was noted that the immunodeficient subjects demonstrated the mean LAK-cell activity of approximately 65% as compared to the control subjects. Upon presenting Thymosin Alpha-1 to the test subjects, researchers observed that it did not significantly improve the levels of NK or LAK cells. Only 3 test subjects were reported to exhibit improved LAK-cell activity by up to 30% whereas others were not significantly impacted. Thymosin Alpha-1 Peptide and Hepatitis Clinical trials were conducted in test subjects with liver complications, with some exhibiting Hepatitis B & C. Tα 1 was presented to the subjects to explore its potential mechanism of action on these complications.(2) For subjects exhibiting Hepatitis B, it was reported by the research team that when these subjects were presented with Thymosin Alpha-1 twice a week for the duration of the study, the reported virological response rate of the subjects appeared increased by 40.6%. For Hepatitis C, subjects reportedly exhibited improved results when Tα 1 was present in combination with interferon alpha compounds. Thymosin alpha-1's apparent role in modulating the immune system was further explored through its potential engagement with toll-like receptors (TLR)-2 and TLR-9 on dendritic cells and other antigen-presenting cells. This interaction potentially initiates a cascade of immune responses, including the stimulation of cytokines such as interleukin-2 (IL-2), IL-10, and interferon-gamma (IFN-γ), which in turn may support the adaptive immune system. Such modulation is crucial not just for combating infections but also for controlling inflammatory responses, potentially benefiting chronic hepatitis and acute pancreatitis due to its apparent actions on cytokine profiles. In murine models and in vitro studies, Thymosin alpha-1 has been shown to possibly stimulate T-cell maturation and enhance the efficacy of natural killer cells. It might also play a role in reducing inflammatory cytokines such as tumor necrosis factor-alpha, which could be particularly beneficial in chronic inflammatory models. Thymosin Alpha-1 Peptide and Sepsis In a 2015 study,(6) a meta-analysis was conducted where all the relevant clinical trials prior to 2014 were analyzed to understand the possible mechanism of Thymosin Alpha-1 in relation to the sepsis reaction. In this study, 12 controlled trials were evaluated in total. Based on the extracted data and assessment, it was observed by the research analysts that there was a reported significant decline in mortality rate amongst test subjects following introduction to Thymosin Alpha-1. Subsequent studies and systematic reviews, such as those conducted by Yu et al., have supported the hypothesis that Tα1 could alleviate the immunosuppression associated with severe sepsis. However, all these studies were conducted on an exceedingly small pool of test subjects. Given the complex immune dynamics during sepsis, characterized by an initial hyperinflammatory response followed by a phase of immunosuppression, it is plausible that Tα1's potential could be highly dependent on the timing of exposure. Addressing this aspect, further investigations are required to establish a more detailed understanding of how Tα1 influences immune pathways during different stages of sepsis. Thymosin Alpha-1 Research with HIV A study(7) consisted of a randomized phase II open-label clinical trial on 20 clinically stable test subjects. These patients were already undergoing highly active antiretroviral (HAART), alongside which Thymosin Alpha-1 peptide was presented to monitor the impact of the combination. Thymosin Alpha-1 was presented two times in a week in 13 subjects. The remaining 7 subjects were given placebo. Every 2 weeks, the cell counts of CD4/CD8 cells, CD45 cells and signal joint T-cell receptor circles (sjTREC) levels were monitored. After 12 weeks, it was reported by the researchers that there were no apparent significant changes in the levels of CD4, CD and CD45 levels in both the peptide or the placebo group. However, the sjTREC levels reportedly increased in the subjects presented with the peptide. These elevated levels of sjTREC might potentially stimulate immune responses. This increase in sjTREC levels hints at the possibility that Thymosin Alpha-1 may contribute to immune reconstitution by enhancing thymic output. However, this change did not correspond with an increase in total T-cell numbers or significant changes in the proportions of naive and memory T-cell phenotypes. Researchers posited that while the rise in sjTREC levels might indicate a modest improvement in thymopoiesis, the overall recovery and functionality of the T-cell compartment appeared largely unchanged within the duration of this study. Thymosin Alpha-1 and Cancer Cells In a study,(8) the levels of the reactive oxygen species (ROS) were monitored in test models after the presentation of Tα 1. During this study, Thymosin Alpha-1 was presented in mice with liver carcinoma. Both the leukomonocytes and HepG2 cells, given the peptide, were isolated from the mouse spleens, for the purpose of this study. Upon analysis, it was observed by the researchers that the ROS level appeared to be significantly higher in the isolated leuko-monocytes, whereas it was apparently lower in the HepG2 cells. Also, the peptide appeared to possibly increase the levels of the leuko-monocytes, whereas it may have delayed the cell cycle for HepG2 cells and thereby reduced their levels in the system. The study also delved into the possible molecular pathways affected by these changes in the redox state. Particularly, the Akt signaling pathway, known to be influenced by ROS, was examined. It was found that in HepG2 cells, there was a dephosphorylation of Akt at Ser473 following Tα1 exposure, suggesting a decrease in Akt activity associated with lowered oxidative stress. This dephosphorylation of Akt might underpin the reduced proliferation seen in these cancer cells. Another laboratory study focused on lung cancer cells (A549), in order to investigate the potential of Thymosin Alpha-1 on cell proliferation, antioxidant enzyme activities, and cell migration.(9) The study's findings suggest that Thymosin Alpha-1 potentially exhibits an anti-proliferative action on A549 cells, particularly at concentrations of 24 and 48 μg/mL, which apparently led to a reduction in cell viability after 24 hours of exposure. Additionally, Thymosin Alpha-1 is posited to enhance the activity of several key antioxidant enzymes. For instance, increases in the activity levels of catalase were observed at concentrations of 12 μg/mL, suggesting a possible strengthening of the cells' oxidative stress response. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) also showed possible enhancements at concentrations of 6 and 12 μg/mL. These findings indicate that Thymosin Alpha-1 might contribute to the cellular antioxidant defense by mitigating the adverse actions of reactive oxygen species (ROS). Regarding cell migration, Thymosin Alpha-1 potentially inhibits the migration of A549 cells in a concentration-dependent manner, as indicated by scratch assays. In terms of ROS production, the study suggests that Thymosin Alpha-1 might lead to a reduction in cellular ROS levels, and this outcome further supports the notion that Thymosin Alpha-1 could play a role in moderating oxidative stress within cancer cells. Thymosin Alpha-1 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Immunodeficiency, British Society for Immunology. Published March 2017. https://www.immunology.org/policy-and-public-affairs/briefings-and-position-statements/immunodeficiency Dominari A, Hathaway Iii D, Pandav K, Matos W, Biswas S, Reddy G, Thevuthasan S, Khan MA, Mathew A, Makkar SS, Zaidi M, Fahem MMM, Beas R, Castaneda V, Paul T, Halpern J, Baralt D. Thymosin alpha 1: A comprehensive review of the literature. World J Virol. 2020 Dec 15;9(5):67-78. doi: 10.5501/wjv.v9.i5.67. PMID: 33362999; PMCID: PMC7747025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747025/ National Center for Biotechnology Information. "PubChem Compound Summary for CID 16130571, Thymalfasin" PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Thymalfasin Garaci E. Thymosin alpha1: a historical overview. Ann N Y Acad Sci. 2007 Sep;1112:14-20. doi: 10.1196/annals.1415.039. Epub 2007 Jun 13. PMID: 17567941. https://pubmed.ncbi.nlm.nih.gov/17567941/ Eckert K, Schmitt M, Garbin F, Wahn U, Maurer HR. Thymosin alpha 1 effects, in vitro, on lymphokine-activated killer cells from patients with primary immunodeficiencies: preliminary results. Int J Immunopharmacol. 1994 Dec;16(12):1019-25. doi: 10.1016/0192-0561(94)90081-7. PMID: 7705963. https://pubmed.ncbi.nlm.nih.gov/7705963/ Li C, Bo L, Liu Q, Jin F. Thymosin alpha1 based immunomodulatory therapy for sepsis: a systematic review and meta-analysis. Int J Infect Dis. 2015 Apr;33:90-6. doi: 10.1016/j.ijid.2014.12.032. Epub 2014 Dec 19. PMID: 25532482. https://pubmed.ncbi.nlm.nih.gov/25532482/ Chadwick D, Pido-Lopez J, Pires A, Imami N, Gotch F, Villacian JS, Ravindran S, Paton NI. A pilot study of the safety and efficacy of thymosin alpha 1 in augmenting immune reconstitution in HIV-infected patients with low CD4 counts taking highly active antiretroviral therapy. Clin Exp Immunol. 2003 Dec;134(3):477-81. doi: 10.1111/j.1365-2249.2003.02331.x. PMID: 14632754; PMCID: PMC1808897. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808897/ Qin Y, Chen FD, Zhou L, Gong XG, Han QF. Proliferative and anti-proliferative effects of thymosin alpha1 on cells are associated with manipulation of cellular ROS levels. Chem Biol Interact. 2009 Aug 14;180(3):383-8. doi: 10.1016/j.cbi.2009.05.006. Epub 2009 May 12. PMID: 19442654. https://pubmed.ncbi.nlm.nih.gov/19442654/ Kharazmi-Khorassani J, Asoodeh A. Thymosin alpha-1; a natural peptide inhibits cellular proliferation, cell migration, the level of reactive oxygen species and promotes the activity of antioxidant enzymes in human lung epithelial adenocarcinoma cell line (A549). Environ Toxicol. 2019 Aug;34(8):941-949. doi: 10.1002/tox.22765. Epub 2019 May 8. PMID: 31067016. 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.