Peptides
Thymagen (20mg)
Thymagen, also known as EW (Glu-Trp), is a synthetically formulated bioregulator peptide, classified within the group of Khavinson peptides. It is an artificial peptide analog of the thymus-derived polypeptide, thymalin, and is noted for its potential immunomodulating characteristics. Thymagen’s role in immune system modulation is becoming increasingly recognized. It seems to interact with key immune processes, potentially modifying immune responses and defense mechanisms. This includes the possibility of altering immune cell activities and influencing the production of various cytokines. In cellular studies, Thymagen research has suggested its potential action on immune regulation, positing its involvement in reinforcing the natural defense mechanisms. Chemical Makeup Molecular formula: C16H19N3O5 Molecular weight: 333.3 g/mol Sequence: Glu-Trp Other known titles:Oglufanide, Thymogen Research and Clinical Studies Thymagen and Immune Cells The research on Thymagen may indicate a potential influence on cyclic nucleotide systems in murine models, which is particularly noted in the context of anaphylaxis and sensitization. In such models, Thymagen, along with other peptide substances with similar potential like thymalin and vilosen, possibly affects the catabolic processes of cyclic nucleotides. In sensitized animals, researchers have noted an apparent decrease in the ratio of cyclic adenosine monophosphate (cAMP) to cyclic guanosine monophosphate (cGMP). Thymagen's potential role in this process appears to be connected to a modulation of this ratio. When anaphylaxis occurs, the cAMP/cGMP ratio apparently returns to a reference level, implying a balancing action. Further, Thymagen may potentially contribute to the increased activity of enzymes responsible for cyclic nucleotide catabolism in lymphocytes of sensitized murine models. This tendency towards an increase is also posited in lymphocytes of murine models of anaphylaxis.(1) Apart from anaphylaxis and hypersensitivity models, Thymagen has also been researched regarding its potential action in models of bacterial infections. According to one trial, Thymagen may have a potential immunoregulatory action in murine models of Yersinia enterocolitica infection. This potential might include a reduction in the polyclonal immune response and the development of autoimmune reactions. Notably, Thymagen appeared to have promoted the intensive development of delayed hypersensitivity in a model of enteral infection with Yersinia enterocolitica. However, it is important to note that this action did not appear to manifest in all cases. Furthermore, Thymagen appeared to have enhanced the nonspecific resistance of the murine models. This enhancement may have potentially contributed to a decrease in the spread of the infective agents across various organs and tissues and facilitated their subsequent elimination from the murine models.(2) Thymagen may also have potential to regulate immunological processes, particularly in the context of T-lymphocyte differentiation and secondary immunodeficiency in experimental models of autoimmune conditions. It is posited that Thymogen may act to modulate certain immune responses, thereby reducing potential secondary immune deficit in these models. The researchers commented that “clinical effect […] was registered in 94.4%, laboratory effect in 83.3%” in tested models.(3) Other experiments have also investigated scenarios involving secondary immunodeficiency, particularly in models of fungal infections like candidiasis. The underlying hypothesis of one such study posits that Thymogen might possibly activate the immunocompetent system, including the thymus. This activation is thought to potentially contribute to the mitigation of the severity of candidiasis. In murine models, where secondary immunodeficiency is induced and followed by the development of candidiasis, Thymogen has been suggested to affect the course of the infection. The observations suggest that after exposure to Thymogen, the severity of candidiasis in these models might be reduced. This outcome implies that Thymogen may have a role in bolstering the immune response, particularly in fungal infection models.(4) Thymagen and Cardiac Cells Thymagen may have shown potential in addressing various types of arrhythmias in murine models. This potential has been posited through its examination in six distinct arrhythmia models. These models include those apparently induced by agents like aconitine, calcium chloride, strophanthin, scenarios of low sodium levels, reperfusion, and epinephrine administration. These agents are also known to induce ischaemia and therefore used to model arrhythmia. Yet, more trials are needed to evaluate and access these findings. The scientists specifically noted that “The mechanism of the Thymogen anti-ischemic action is realized without the participation of the opiate receptors and blockade of calcium entrance into the cardiomyocytes.”(5) Thymagen and Tumor Cells A study in murine models which underwent exposure of N-nitrososarcosine ethyl ester (NSEE) reported an apparent induction of the formation of papilloma cells and carcinoma cells in cultures from esophagus cell lines. The researchers reported that Thymagen apparently decreased the occurrence of such tumor cells by roughly 12% and seemingly reduced the tumor multiplicity by 1.7 times.(6) In another study involving murine models and Thymagen, the models were exposed to high levels of radiation exposure from radionuclide over 12 months, ultimately inducing the formation of cancer cells. Some of these models were also apparently introduced with Thymagen for five consecutive days each month, alongside the radionuclide exposure. The results from this study suggested that the murine models exposed to radionuclides alone exhibited a higher occurrence of tumor cells generally, and especially in cell lines from breast tissue. Conversely, in the rats that were also exposed to Thymagen alongside the radionuclides, there appeared to be a reduction in both the total number of tumor cells and their incidence. Furthermore, the study posited that murine models exposed only to Thymagen (without radionuclide exposure) appeared to exhibit an apparently longer lifespan, a slower aging rate, and a lower overall occurrence of tumor cells, both malignant and benignant. This finding may highlight Thymagen's potentially broader role in influencing aging and tumor development, beyond its apparent interaction with radiation-induced carcinogenesis.(7) A third study explored the potential of Thymagen, particularly focusing on its action on cellular immunity in the context of subjects with solid tumors in the abdominal cavity and retroperitoneal space, specifically before manual excision. Study findings following Thymagen exposure for seven days suggest that it may potentially aid in restoring the structural and functional parameters of cellular immunity, when compared to a placebo group. This potential is indicated by a reduction in the number and severity of complications observed in the study, as well as a possible shortening of the recovery period following an excision.(8) Thymagen peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Demidov, S. V., Kostromin, A. N., Kuĭbeda, V. V., Chernaia, I. V., & Borovok, M. I. (1991). Vliianie timagena, timalina i vilozena na soderzhanie cAMP, cGMP i aktivnost' fosfodiésteraz v limfotsitakh selezenki pri sensibilizatsii i anafilakticheskom shoke [Effect of thymagen, thymalin and vilosen on the cAMP and cGMP levels and phosphodiesterase activity in spleen lymphocytes during sensitization and anaphylactic shock]. Ukrainskii biokhimicheskii zhurnal (1978), 63(4), 104–106. https://pubmed.ncbi.nlm.nih.gov/1659006/ Iushchuk, N. D., Tseneva, G. I.a, Alenushkina, T. V., & Kuliashova, L. B. (1995). Effektivnost' primeneniia timogena pri éksperimental'noĭ infektsii, vyzvannoĭ Yersinia enterocolitica [The efficacy of using thymogen in an experimental infection caused by Yersinia enterocolitica]. Zhurnal mikrobiologii, epidemiologii i immunobiologii, (3), 106–108. https://pubmed.ncbi.nlm.nih.gov/7660690/ Zhuk, E. A., & Galenok, V. A. (1996). Timogen v lechenii sakharnogo diabeta I tipa [Thymogen in the treatment of type-1 diabetes mellitus]. Terapevticheskii arkhiv, 68(10), 12–14. https://pubmed.ncbi.nlm.nih.gov/9026934/ Khmel'nitskiĭ, O. K., Iakovlev, G. M., Belianin, V. L., Khavinson, V. K.h, Morozov, V. G., & Deĭgin, V. I. (1990). Vliianie sinteticheskogo peptida timusa (timogena) na immunnuiu sistemu pri kandidoze v usloviiakh immunodepressii [The effect of a synthetic thymus peptide (thymogen) on the immune system in candidiasis under immunodepression]. Arkhiv patologii, 52(1), 20–25. https://pubmed.ncbi.nlm.nih.gov/2337388/ Filippova, O. V., Reznikov, K. M., Alabovskił, V. V., Khamburov, V. V., & Vinokurov, A. A. (1997). Vliianie timogena na sostoianie serdtsa pri ishemii i reperfuzii [The effect of thymogen on the heart in ischemia and reperfusion]. Eksperimental'naia i klinicheskaia farmakologiia, 60(3), 27–29. https://pubmed.ncbi.nlm.nih.gov/9324392/ Bespalov, V. G., Troian, D. N., Petrov, A. S., Morozov, V. G., & Khavinson, V. K.h (1989). Ingibiruiushchiĭ éffekt timogena na razvitie opukholeĭ pishchevoda i predzheludka, indutsirovannykh étilovym éfirom N-nitrozosarkozina u krys [Inhibiting effect of thymogen on the development of tumors of the esophagus and forestomach induced by N-nitrososarcosine ethyl ester in rats]. Eksperimental'naia onkologiia, 11(4), 23–26. https://pubmed.ncbi.nlm.nih.gov/2759010/ Anisimov, V. N., Miretskiĭ, G. I., Morozov, V. G., Pavel'eva, I. A., & Khavinson, V. K.h (1992). Vliianie sinteticheskogo immunomoduliatora timogena na radiatsionnyĭ kantserogenez u krys [The effect of the synthetic immunomodulator thymogen on radiation-induced carcinogenesis in rats]. Voprosy onkologii, 38(4), 451–458. https://pubmed.ncbi.nlm.nih.gov/1300740/ Smirnov, V. S., Petlenko, S. V., & El'tsin, S. S. (2011). Advances in gerontology = Uspekhi gerontologii, 24(2), 278–284. https://pubmed.ncbi.nlm.nih.gov/21957588/ 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-2 Blend (10mg)
Sermorelin is a research peptide made of 29 amino acids that is a truncated version of the full 44-aa length endogenous Growth Hormone-Releasing Hormone (GHRH). Sermorelin is considered the shortest functional analogue that contains the first 29 amino acids, and it is also amidated at the C-terminus. According to research by Clark et al., the peptide appears to retain its affinity to the GHRH receptors found in pituitary cells and activate them.(1) Thus, Sermorelin is considered a GHRH analog. GHRH receptors are the main receptors on pituitary cells that are considered to play a role in the synthesis of growth hormone. Research by Berlanga-Acosta et al. describes GHRP-2 as a fully synthetic hexapeptide, developed from earlier GHRPs such as GHRP-6 and ultimately based on modified enkephalins (endogenous opioid pentapeptides).(2) It is engineered to favor growth hormone release rather than opioid activity, apparently by targeting ghrelin (growth hormone secretagogue) receptors instead of classical opioid receptors. Because GHRP-2 and related GHRPs share this receptor system, they are broadly referred to as growth hormone secretagogues (GHSs). Researchers suggest that by targeting different pituitary receptors with the same potential, peptides like Sermorelin and GHRP-2 may have synergistic actions. Future research should elucidate this more thoroughly. Chemical Makeup Other Known Titles Sermorelin: GRF 1-29 NH2 GHRP-2: pralmorelin Molecular Weight: Sermorelin:93 g/mol GHRP-2:97 g/mol Molecular Formula: Sermorelin: C149H246N44O42S GHRP-2: C45H55N9O6 Research and Clinical Studies Sermorelin & GHRP-2 Actions on Pituitary Cells Sermorelin appears to act primarily at GHRH receptors, which normally respond to endogenous GHRH. Work by Culhane et al. suggests that GHRH analogs may interact with the receptors via G-protein coupling, followed by cAMP production, and downstream growth hormone release. (3) Consequently, the upregulated growth hormone release may interact with growth hormone receptors in a variety of cells, which may synthesize a major anabolic mediator called insulin-like growth factor-1 (IGF-1). By contrast, GHRP-2 is thought to target the ghrelin receptors, which are also known as growth-hormone secretagogue receptors. Specifically, these are the GHS receptors 1a. Research by Yin et al. has deeply investigated these receptors, and they posit that these are seven-transmembrane G-protein-coupled receptors.(4) The interaction may then trigger a chain of intracellular signals starting with an enzyme at the cell membrane called phospholipase C (PLC). PLC cuts a specific membrane fat molecule (PIP₂) into two smaller signaling molecules. One molecule, called IP₃, moves into the fluid inside the cell and may ultimately bind to channels on internal calcium stores, causing Ca²⁺ to be released into the cytoplasm. The other fragment, called DAG, stays in the membrane and helps switch on another enzyme family called protein kinase C (PKC), which adds phosphate groups to selected proteins and thereby changes their activity. In combination, the temporary rise in intracellular calcium and the activation of PKC may activate the genes associated with growth hormone synthesis and also stimulate the release of growth hormone molecules out of the pituitary cells. Sermorelin & GHRP-2 Potential on Somatotroph Growth Hormone Output Vittone et al. explored the potential of Sermorelin on the growth hormone output capacity of pituitary cells and suggest that the peptide may double it.(5) Specifically, the researchers commented that 12-hour mean growth hormone concentration increased from 1.1 ± 0.9 µg/L to 2.2 ± 1.9 µg/L, and the integrated growth hormone secretion over 12 hours. increased from 1114 ± 931 µg·min/L to 2032 ± 1728 µg·min/L. This apparent increase in GH synthesis and release per pulse was accompanied by “no change in GH pulse frequency or in levels of IGF-I, IGFBP-3, or GHBR.” Nevertheless, the authors posited that local, tissue-level IGF-I production in targets such as skeletal muscle cells might still be modulated, even if overall IGF-I remains relatively stable. The researchers also posited that if muscle cells are exposed to the GH peaks induced by Sermorelin, this may be associated with better-supported muscle cell performance. According to further research by Khorram et al., the majority of the increase in GH synthesis may be within the first 2 hours of the pituitary cells being exposed to Sermorelin.(6) The integrated 2-hour GH area observed by the authors apparently rose from about 200-300 to 1,100–1,600 µg·L⁻¹·min (roughly 6-fold). Additionally, this team of researchers also observed an increase in the IGF-1. Mean IGF-I rose apparently by about 27-28%. According to the available research, such as experiments by Bowers et al., GHRP-2 may also upregulate growth hormone synthesis by pituitary cells.(7) Particularly in the case of continuous exposure for 24 hours, the peptide apparently led to an increase from roughly 20–30 µg·L⁻¹·24 h under placebo conditions to about 120–180 µg·L⁻¹·24 h with GHRP-2, implying an approximate 4- to 6-fold rise in growth hormone production. This pattern is compatible with a sustained stimulatory action on growth hormone synthesis by pituitary cells and pulsatile release rather than a brief, desensitizing spike. In the same experiment, IGF-1 concentrations apparently rose from baseline values of about 90–100 µg/L to approximately 150–160 µg/L after the extended 24-hour GHRP-2 exposure. This data suggests that GHRP-2 may increase IGF-1 production by roughly 50–80%, creating a higher steady-state plateau of IGF-1. Sermorelin & GHRP-2 Potential on Other Cells In laboratory settings studied by Chatelain et al., upregulation of IGF-1 by peptides such as Sermorelin may extend beyond pituitary cells and growth hormone dynamics. It might potentially support Leydig cells and their main endocrine function, which is to synthesize testosterone.(8) The increased IGF-1 may act on Leydig cells via the IGF-1 receptor, which is thought to be present on these cells, and has been posited to support their responsiveness to gonadotropins. Experimental data suggest that sustained elevations in growth hormone and IGF-1 may increase LH/hCG receptor density in Leydig cells and may raise hCG-stimulated hormonal output per cell, specifically the hormone testosterone. This pattern is compatible with the possibility that IGF-1 modulates transcription, translation, or membrane trafficking of LH/hCG receptors, thereby amplifying gonadotropin signaling at the Leydig cell surface. In parallel, IGF-1 may also promote expansion of Leydig cell mass and/or support their functional maturation, perhaps through modest mitogenic or differentiation-supporting pathways. However, these mechanisms remain hypothetical and would require targeted verification in controlled laboratory models. Experimental work with GHRP-2 also suggests that this peptide may interact with receptors outside pituitary cells. Specifically, research by Granado et al. suggests that the peptide may modulate liver-associated immune cells during an inflammatory challenge with lipopolysaccharide (LPS).(9) In LPS-stimulated hepatocyte–nonparenchymal cocultures, GHRP-2 apparently reduced TNF-α mRNA and nitrite/nitrate release, which are important inflammatory markers. Researchers like these also tend to express through their research the theory that GHRP-2 may act primarily on nonparenchymal immune cells (such as Kupffer or Kupffer-like macrophages) rather than directly on hepatocytes. Separate lines of research have proposed that GHRP-type peptides may bind CD36 on macrophages, so it is plausible that, in such models, GHRP-2 may signal via CD36 on these immune cells, dampening LPS-driven activation programs that lead to TNF-α and inducible nitric oxide synthase induction. The downstream normalization of nitric oxide and cytokine output may then secondarily interact with neighboring hepatocytes in cell cultures, including their IGF-I expression. Sermorelin & GHRP-2 Synergistic Potential The already mentioned work in experimental pituitary systems by Bowers et al. has explored how GHRP-2 may behave when combined with endogenous GHRH. They observed that simultaneous exposure to GHRP-2 and unmodified GHRH may raise integrated 24-hour growth hormone output from baseline values of roughly 20–30 µg·L⁻¹ to about 238 ± 28 up to 452 ± 106 µg·L⁻¹. These findings correspond to an apparent ~16-fold elevation over baseline GH exposure and more than a twofold increase compared with GHRP-2 alone. Thus, the concurrent activation of the GHS-R1a and the GHRH receptor on pituitary cells may exert synergistic actions to generate a markedly amplified growth hormone secretion in laboratory settings. The researchers also concluded that the “combined GHRP-2 and GHRH drive is more effective than either agonist alone.” Laboratory work by Veldhuis et al., using a similar experimental setting, also points to a potentially synergistic interaction between GHRP-2 and full-length GHRH at the level of pituitary cell cultures. In their experimental models, GHRH alone was estimated to increase growth hormone burst by roughly 20-fold over baseline, whereas GHRP-2 alone was associated with an even larger 47-fold rise. When both secretagogues were present together, the calculated response increased to around 54-fold above saline, which was on the order of 10–15% higher than GHRP-2 alone. This pattern is also compatible with the theory that while each peptide strongly activates somatotroph signaling on its own, combined receptor engagement may provide an additional amplification of growth hormone release. By extension, the GHRH-analog Sermorelin should also exert synergistic potential when combined in experiments at the pituitary-cell level. To confirm this, a small clinical series by Sigalos et al. specifically investigated Sermorelin with GHRP-2 (plus an additional GHRP).(11) According to their data, the combination may drive a substantially stronger IGF-1 response than GHRP-2 alone. Apparently, Sermorelin, GHRP-2, and another GHRP increased IGF-1 from about 160 ng/mL at baseline to roughly 250–265 ng/mL. This is interpreted as roughly a 50–70% rise and a clear upward shift within the reference range. These data points are compatible with the notion that dual-pathway stimulation of pituitary somatotrophs may produce a markedly greater IGF-1 increase than either peptide alone. However, this study is not able to prove superiority because it lacked adequate levels of experimentation. Sermorelin & GHRP-2 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 human growth hormone releasing factor in normal and GHRF-deficient rats. Nature. 1985 Mar 21-27;314(6008):281-3. doi: 10.1038/314281a0. PMID: 2858818. Berlanga-Acosta J, Abreu-Cruz A, Herrera DGB, Mendoza-Marí Y, Rodríguez-Ulloa A, García-Ojalvo A, Falcón-Cama V, Hernández-Bernal F, Beichen Q, Guillén-Nieto G. Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects. Clin Med Insights Cardiol. 2017 Mar 2;11:1179546817694558. doi: 10.1177/1179546817694558. PMID: 28469491; PMCID: PMC5392015. 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. 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 Chatelain PG, Sanchez P, Saez JM. Growth hormone and insulin-like growth factor I treatment increase testicular luteinizing hormone receptors and steroidogenic responsiveness of growth hormone deficient dwarf mice. Endocrinology. 1991 Apr;128(4):1857-62. doi: 10.1210/endo-128-4-1857. PMID: 2004605. Granado M, Martín AI, López-Menduiña M, López-Calderón A, Villanúa MA. GH-releasing peptide-2 administration prevents liver inflammatory response in endotoxemia. Am J Physiol Endocrinol Metab. 2008 Jan;294(1):E131-41. doi: 10.1152/ajpendo.00308.2007. Epub 2007 Nov 6. PMID: 17986630. 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.
Chonluten (20mg)
Chonluten, also known as EDG tripeptide or T-34, is a tripeptide that may potentially regulate the physiological processes of the respiratory system by influencing inflammation and proliferation. It may potentially restore mechanisms of anabolism and catabolism, critical to functional tissues. Chonluten is a peptide complex containing glycine, glutamine, and asparagine, which is considered to normalize the performance of bronchial mucous membrane cells.(1) Chonluten has been primarily researched for its potential to normalize the impact on target organs by replacing or supporting the activity of substances secreted by these morphological structures through immunomodulation. It may possibly increase the lifespan of mesenchymal stem cells (MCS) and possibly induce molecular mechanisms that contrast senescence. Chonluten appears to be organ-specific, with its primary potential exhibited in lung tissues, possibly extending action in the gastrointestinal tract.(2) Chonluten may revitalize, regulate, and otherwise provide favorable actions on the airway and bronchial mucosa. Chemical Makeup(3) Molecular Formula: C11H17N3O8 Molecular Weight: 319.27 g/mol Structure: 4S)-4-amino-5-[[(2S)-3-carboxy-1-(carboxymethyl amino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Other Known Titles: Glu-asp-gly, Glutamyl-aspartyl-glycine, H-Glu-asp-gly-OH, T-34 tripeptide Research and Clinical Studies Chonluten Peptide and Inflammation Reduction As lung capacity reduces, researchers suggest Chonluten may decrease the rate of cell death while encouraging proliferative activity via protection of the bronchial lining. (1) The bronchial inner lining is a barrier between the external environment and internal structures. Different inflammatory conditions may affect this inner lining and change mucus production and the structure of the cells’ extracellular matrix. Chonluten's proposed mechanisms of action may help reduce levels of inflammation within the lungs. One such potential mechanism of action may be the initiation of phosphorylation in STAT molecules, especially STAT1, within immune cells called macrophage cells. STAT stands for "Signal Transducer and Activator of Transcription.” These molecules appear to be messengers inside the cells, mediating signals and passing them to the cellular nucleus. Thus, STAT1 works like a switch that turns on genes, and it might work together with other proteins to send immune signal messages into the macrophage cell's nucleus, ultimately regulating this type of immune cell and reducing inflammation. The researchers also theorized that Chonluten may potentially decrease the activation of STAT3, another important protein that may act like a gene switch. STAT3 is involved in quick immune responses and might help control the gene for IL-6 (interleukin-6), an important immune system protein during inflammation. By affecting STAT3, Chonluten might change how IL-6 works, which could help reduce inflammation. Further, the researchers suggest Chonluten might exhibit some capacity to reduce levels of IL-6, TNF (tumor necrosis factor), and IL-17 in immune cells triggered by bacterial and other foreign substances. IL-6, TNF, and IL-17 are all proteins that scientists consider to cause inflammation and help regulate the immune system. Lowering the levels of these proteins may help calm inflammation in these activated immune cells. The scientists commented that the peptide apparently “inhibited in vitro tumor necrosis factor (TNF) production of monocytes exposed to pro-inflammatory bacterial lipopolysaccharide (LPS). The low TNF release by monocytes is linked to a documented mechanism of TNF tolerance, promoting attenuation of inflammatory action." Chonluten might also reduce the sticking process between the inner lining of blood vessels and immune cells. This was first posited by researchers who observed Chonluten mixed with endothelial cells (cells lining blood vessels) in experiments. By changing how these cells stick to each other, Chonluten may potentially affect how immune cells move and travel around the organism, which may be important in controlling inflammation and immune reactions.(1) Chonluten Peptide and Gastrointestinal Tract Tissues Chonluten's suggested impact on the gastrointestinal tract is reportedly similar to that in the lungs, with studies positing its potential to reduce inflammation and prevent the prevalence of vascular changes that induce inflammatory diseases. For example, Chonluten might help repair cells in the stomach and intestinal tissues. It is posited to do this by controlling the activity of genes linked to antioxidant enzymes like superoxide dismutase (SOD). Research on Chonluten suggests that it might normalize these genes, helping to balance antioxidant defenses in the stomach lining. This might reduce oxidative stress, which harms cells, and encourage cell repair. It is also believed that Chonluten may reduce inflammation by affecting inflammation-related genes, such as TNF-α and cyclooxygenase-2 (Cox-2). By lowering the activity of these inflammation-causing substances, Chonluten might help control stomach tissue inflammation, aiding in cell repair. Additionally, Chonluten may promote new tissue growth, important for healing damaged areas. It might encourage the multiplication of fibroblasts, which are cells that help in tissue repair and the growth of new blood vessels in the healing tissue. It may also help repair damaged stomach lining by stimulating the growth of epithelial cells, which could lead to the recovery of damaged and ulcerated tissues. Furthermore, Chonluten may reduce excessive cell death (apoptosis) in the stomach lining. It is thought to possibly regulate the expression of heat shock protein 70 (HSP70), which protects cells from triggers that cause apoptosis. By controlling HSP70, Chonluten may possibly prevent excess cell death and promote the survival and repair of gastrointestinal tract tissues.(2) Chonluten Peptide and Gene Expression Short peptides, such as Chonluten, have been researched in the context of certain modes of DNA expression, such as DNA methylation.(4)(5) Research suggests that “Short peptides, consisting of 2-7 amino acid residues, can penetrate into the nuclei and nucleoli of cells and interact with the nucleosome, the histone proteins, and both single- and double-stranded DNA. DNA-peptide interactions, including sequence recognition in gene promoters, are important for template-directed synthetic reactions, replication, transcription, and reparation. Peptides can regulate the status of DNA methylation, which is an epigenetic mechanism for the activation or repression of genes in both the normal condition, as well as in cases of pathology and senescence.”(4) Chonluten Peptide and the Immune System Research studies suggest that Chonluten may regulate the immune system, stimulating or suppressing it to respond to advancing conditions. Chonluten's possible mechanisms of action have been suggested to be mediated by many genes, including heat shock protein, gene HSP70, SOD, c-Fos, antioxidative system genes, and TNF-alpha. The regulation of such genes may result in anti-inflammatory impacts, particularly c-Fos—a protein bioregulator of cell differentiation, survival, and proliferation that is activated in response to hypoxia and cellular damage. Although c-Fos may induce the growth of new blood vessels and cell proliferation locally in response to an injury, progressive expression might result in thickened bronchial mucosa or cancer.(2) Chonluten Peptide and Aerobic Activity Research studies have grappled with the role of Chonluten peptide in various aerobic studies: “Studies have [suggested] that several bioactive peptides elicit strongly upregulating effects on muscle protein synthesis or increase muscular strength and recovery [...] Besides positive effects on [contractile] strength and recovery, recent investigations found that hydrolyzed proteins might also influence endurance performance and metabolism.”(6) Further research indicates that the Chonluten tripeptide might reduce stress hormone secretion and potentially improve the organism’s tolerance to low oxygen conditions. This suggests that the Chonluten tripeptide could help the lung and muscle tissues work better when insufficient oxygen exists. For example, researchers share that the Chonluten tripeptide may possibly exert a protective effect against low oxygen stress, which might stem from the peptide’s potential to control the activity of certain genes. These genes may include the c-Fos gene, which is involved in cell growth and survival; the heat shock protein gene HSP70, which might protect cells from low oxygen stress; genes that make enzymes in internal antioxidant systems, like SOD and COX-2, which are considered to help protect against oxidative damage; and the tumor necrosis factor gene TNF-α, which is believed to be important in inflammation and immune response. These findings suggest that the Chonluten tripeptide might potentially influence various biological processes, contributing to what seems to be its effect in protecting against low oxygen stress. (7) Chonluten peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References Avolio F, Martinotti S, Khavinson VK, Esposito JE, Giambuzzi G, Marino A, Mironova E, Pulcini R, Robuffo I, Bologna G, Simeone P, Lanuti P, Guarnieri S, Trofimova S, Procopio AD, Toniato E. Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line. Int J Mol Sci. 2022 Mar 25;23(7):3607 V. K. Khavinson, N. S. Lin’kova, A. V. Dudkov, V. O. Polyakova, and I. M. Kvetnoi, “Peptidergic regulation of expression of genes encoding antioxidant and anti-inflammatory proteins,” Bull. Exp. Biol. Med., vol. 152, no. 5, pp. 615–618, Mar. 2012, DOI: 10.1007/s10517-012-1590-2 PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 194641, Glutamyl-aspartyl-glycine; [cited 2024 Feb. 20]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Glutamyl-aspartyl-glycine Khavinson VK, Popovich IG, Linkova NS, Mironova ES, Ilina AR. Peptide Regulation of Gene Expression: A Systematic Review. Molecules. 2021 Nov 22;26(22):7053 Khavinson VK, Lin'kova NS, Tarnovskaya SI. Short Peptides Regulate Gene Expression. Bull Exp Biol Med. 2016 Dec;162(2):288-292 König D, Kohl J, Jerger S, Centner C. Potential Relevance of Bioactive Peptides in Sports Nutrition. Nutrients. 2021 Nov 10;13(11):3997. DOI: 10.3390/nu13113997 Khavinson, V., Linkova, N., Dyatlova, A., Kuznik, B., & Umnov, R. (2020). Peptides: Prospects for Use in the Treatment of COVID-19. Molecules (Basel, Switzerland), 25(19), 4389. https://doi.org/10.3390/molecules25194389 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.
AOD 9604 (5mg)
AOD 9604 peptide is a synthetic analog of growth hormone designed with the intention of mitigating obesity and aiding weight loss. The peptide is a modified fragment of the growth hormone where the last 16 amino acids (176-191) have been reproduced as a specific peptide, called GH Fragment 176-191 or simply AOD 9604. It also has a tyrosine residue to replace the first amino acid at the N-terminus, which researchers consider to help increase the stability of the peptide.(1) More specifically, AOD 9604 is considered the lipolytic fragment of GH as different parts of the GH molecule appease to have different potentials. For instance, studies suggest that out of its 191 amino acid structure “the N-terminal region exhibits an insulin-potentiating action, while amino acids 108 - 129 of hGH were found to evoke high mitogenic responses.”(2) Overview AOD 9604 peptide was developed in the 1990s in an effort to develop proteins which might exhibit anti-obesity properties similar to Growth Hormone (hGH). Rigorous scientific studies and experiments have since been conducted to determine the potential action of AOD 9604 in lipolysis.(1) Lipolysis is a term to describe the process through which stored fats or triglycerides in fat cells are broken down into glycerol and free fatty acids, which may be used as an energy source by other cells. Enzymes such as lipase appear to play a critical role in this process, helping in the breakdown of these fats. It's possible that AOD9604 may influence the fat cells and lipolytic receptors, particularly given its observed association with changes in weight and fat in murine models. Research study findings indicate that the fragment seems to have the capacity to amplify lipolytic sensitivity following its introduction. Furthermore, the study hypothesizes a potential interaction of AOD9604 with the beta-adrenergic pathway, especially concerning the beta(3)-adrenergic receptors (beta(3)-AR), which are considered to be key lipolytic receptors found in fat cells. While it is not entirely clear, the expression level of beta(3)-AR RNA, the primary lipolytic receptor in fat cells, was observed to increase in the presence of AOD 9604. This could possibly suggest that the peptide might be playing a role in enhancing the sensitivity of these lipolytic receptors, potentially making them more responsive to lipolytic stimuli. However, it is essential to note that while the peptide appears to elevate the expression of beta(3)-AR, it may not act directly through the beta(3)-AR to induce its potential lipolytic action. Scientists and researchers have suggested that the modified portion of the hGH in the AOD 9604 peptide may be responsible for significantly inducing the fat burning process, possibly without stimulating the production of Insulin-like Growth Factor IGF 1, as opposed to the natural growth hormone. Chemical Makeup Molecular Formula: C78H123N23O23S2 Molecular Weight: 1815.12 g/mol Other Known Titles: Tyr-hGH Fragment 177-191 Research and Clinical Studies AOD 9604 Peptide and Lipolytic Activity Early studies were carried out on obese mice where the AOD 9604 peptide was periodically introduced for 14 days. Following the experiment, the results reported a reduction in weight and excess fat. These results appeared directly correlated with the increased levels of major lipolytic receptors, beta(3)-AR, found in the fat cells. AOD 9604 peptide appeared to exhibit action similar to hGH wherein both may be capable of increasing repressed levels of lipolytic receptors in obese mice as compared to the lean mice. To confirm whether the lipolytic action of AOD 9604 might merely be associated with the increased lipolytic receptor levels, additional studies were carried out where AOD 9604 was given to mice with knocked out lipolytic receptors. Further analysis suggested that the AOD 9604 peptide enacted the lipolytic action via increased energy expenditure and fat oxidation.(1) Both these findings on chronic and acute action of AOD 9604 suggested that while enhanced beta(3)-AR expression may have played a role in the chronic action of the compound, beta(3)-AR might not be the sole arbiter in this reaction. Oxidation and enhanced energy expenditure appeared to be vital in the proposed action of the peptide. In 2000, a research study was carried out in obese Zucker rats where the AOD 9604 peptide was given daily for 19 consecutive days. Following the study, it was reported that weight appeared to be reduced in all rats by over 50%, in comparison to the rats given a placebo. Further analysis suggested that the adipose tissues of the AOD 9604 peptide animals had increased lipolytic activity and no marked insulin sensitivity interruption in the animals.(3) AOD 9604 Peptide and Obesity In 2004, clinical trials observed the actions of the peptide in 300 obese subjects who were given the peptide for 12 weeks. The rate of weight loss remained consistent throughout the study period. The trial results noted minor improvement exhibited in the subjects’ cholesterol profiles and glucose tolerance levels.(4) AOD 9604 Peptide and Cell Regeneration Additional research was conducted to study the regenerative potential of the peptide. In 2015, 32 white rabbits were divided into four groups of eight, and each group was given a placebo, AOD 9604, hyaluronic acid, or a combination of AOD 9604 and hyaluronic acid for 4 to 7 weeks. After the study, these rabbits were assessed morphologically and histopathologically to determine the degree of cartilage degeneration. It was concluded that rabbits given the combination of AOD 9604 with hyaluronic acid apparently exhibited the least degeneration. Thus, it was suggested by the researchers that AOD 9604 might exhibit potential to enhance cartilage regeneration and cartilage repair in some capacity.(5) This may be due to the potential role of AOD 9604 in cellular differentiation processes and, potentially, in the synthesis of proteins important for tissue repair. According to an in vitro study, AOD 9604 may possibly enhance the differentiation of adipose mesenchymal stem cells into bone(5). These stem cells, which are typically found within fat tissue, may have the potential to evolve into various cell types. It has been hypothesized that under the influence of AOD 9604, these stem cells may show a predisposition to differentiate into bone cells. Moreover, when the research was conducted on isolated bovine chondrocytes, it appeared that there might be an increased production of proteoglycan and collagen. Chondrocytes are cells believed to be found within cartilage tissue, and they possibly play a role in producing and maintaining the extracellular matrix, which consists of components like collagen and proteoglycans. It is posited that the presence of AOD 9604 could stimulate these chondrocytes to produce more of these vital components. The study also hints at the idea that AOD 9604 might promote the differentiation of myoblasts into C2C12 cells. Myoblasts are thought to be precursor muscle cells, and C2C12 cells are a type of murine model muscle cell line. From what the study suggests, AOD 9604 may assist in the transition of these precursor cells into a more mature form. The research seems to underline the potential role AOD 9604 might have in processes connected to the repair of bone, cartilage, and muscle tissues. AOD 9604 and Research in Cancer Cells The peptide may be able to bind (target) tumor-related proteins to enhance tumor drug accumulation and local cytotoxicity.(6) The hGH fragment AOD 9604 may potentially play a pivotal role in cancer cell research, as it has been observed to enhance the anticancer efficacy of doxorubicin, a commonly recognized chemotherapeutic agent. One study utilized chitosan nanoparticles, a biocompatible and biodegradable polymer, as a carrier for doxorubicin and AOD 9604.(6) The research team hypothesized that AOD 9604 possibly enhanced the doxorubicin binding to multiple breast cancer cell protein targets, thereby exhibiting greater anti-proliferative activity against the MCF-7 breast cancer cell line compared to chitosan loaded with doxorubicin alone. This suggests that AOD 9604 may potentially augment the anti-cancer potency of doxorubicin while possibly minimizing unintended actions associated with non-target tissue exposure. In conclusion, multiple clinical studies have suggested that the peptide may significantly induce lipolysis and possibly prevent lipogenesis by mimicking natural hGH. AOD 9604 is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Mark Heffernan, Roger J. Summers, Anne Thorburn, Esra Ogru, Robert Gianello, Woei-Jia Jiang, Frank M. Ng, The Effects of Human GH and Its Lipolytic Fragment (AOD 9604) on Lipid Metabolism Following Chronic Treatment in Obese Mice and β 3-AR Knock-Out Mice, Endocrinology, Volume 142, Issue 12, 1 December 2001, Pages 5182–5189. https://pubmed.ncbi.nlm.nih.gov/11713213/ Moré, M. I., & Kenley, D. (2014). Safety and metabolism of AOD9604, a novel nutraceutical ingredient for improved metabolic health. Journal of Endocrinology and Metabolism, 4(3), 64-77. Frank M. Ng, J Sun et.al, Metabolic Studies of a Synthetic Lipolytic Domain (AOD 9604) of Human Growth Hormone, Hormone Research, February 2000. News, Medical and Life Sciences, Obesity drug codenamed AOD 9604 highly successful in trials, 16 December 2004. Dong Rak Kwon and GI Young Park, Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model, Annals of Clinical and Laboratory Science, Volume 45, July-August 2015. Habibullah, M. M., Mohan, S., Syed, N. K., Makeen, H. A., Jamal, Q. M. S., Alothaid, H., Bantun, F., Alhazmi, A., Hakamy, A., Kaabi, Y. A., Samlan, G., Lohani, M., Thangavel, N., & Al-Kasim, M. A. (2022). Human Growth Hormone Fragment 176-191 Peptide Enhances the Toxicity of Doxorubicin-Loaded Chitosan Nanoparticles Against MCF-7 Breast Cancer Cells. Drug design, development and therapy, 16, 1963–1974. https://doi.org/10.2147/DDDT.S367586 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.
Matrixyl (200mg)
Matrixyl, also known as as palmitoyl pentapeptide-4 or palmitoyl pentapeptide-3, is a synthetic peptide currently under scientific investigation for its potential to stimulate collagen production in the skin. It is classified as a matrikine - a messenger peptide that may regulate cell activities by interacting with their specific receptors. Collagen is a protein that is considered to support flexibility and structural integrity in the extracellular matrix of the skin. The conjugation with the palmitoyl introduces the potential for more consistent delivery across the skin and better stability to skin proteases.(1) Chemical Makeup Molecular formula: C39H75N7O10 Molecular weight: 802.05 g/mol Other known titles: Palmitoyl pentapeptide-4, (palmitoyl pentapeptide-3 prior to 2006) Research and Clinical Studies Matrixyl Peptide and Collagen Synthesis Studies suggest that Matrixyl may act as a signal peptide fragment of the C-terminal propeptide of type I collagen.(2) The scientists indicate that it may act by signaling fibroblasts and "stimulates feedback regulation of new collagen synthesis and ECM proteins." Fibroblasts are a type of cell that is found in connective tissue. They play a crucial role in forming and maintaining the extracellular matrix (ECM), a complex network of proteins and carbohydrates that provides structural support to tissues and organs. The main extracellular matrix proteins are collagens, elastins, fibronectins, and laminins. Fibroblasts produce and secrete collagen, the ECM's main structural protein. Collagen provides tensile strength to tissues and organs and is essential for maintaining their shape and integrity. During wound healing, fibroblasts are responsible for depositing new collagen fibers to replace damaged tissue. Researchers suggested that Matrixyl may potentially stimulate collagen production in a concentration-dependent manner close to the critical aggregation concentration, indicating that self-assembly and collagen production are interrelated.(3) Self-assembly of peptides includes hydrogen bonds, electrostatic interactions, hydrophobic interactions, aromatic interactions (π–π stacking), and van der Waals forces. Matrixyl Peptide and Wrinkles Several studies suggest some potential for Matrixyl to induce action on fibroblasts and collagen synthesis. One research study examined its potential in research models of bi-lateral exposure to Matrixyl peptide and placebo, respectively.(5) The study reported that the peptide appeared to have reduced overall wrinkle depth compared to the placebo control. An additional study aimed to investigate the cellular activity of Matrixyl.(6) A compound infused with Matrixyl was introduced twice daily to the periorbital area of the research model for a duration of 8 weeks. The results indicated improvements via the exposure to Matrixyl, which appeared to exhibit better results when compared to other peptides and placebo based on measured data. Another study aimed to isolate the potential of Matrixyl to improve skin surface texture and wrinkle depth in the periorbital region.(7) Two double-blind, randomized, controlled studies were conducted in research models of moderate to distinct periorbital wrinkles. After 4 weeks, the peptide was reported by researchers to have appeared to reduced the texture of periorbital skin and reduced the apparent depth of larger wrinkles. Matrixyl Peptide and Scarring One study investigated the potential of Matrixyl on fibroblast contractility and its potential role in scar formation.(8) Matrixyl was reported to reduce the expression of α-SMA (alpha-smooth muscle actin) and inhibit the trans-differentiation of fibroblasts to myofibroblasts. Scientists indicate alpha smooth muscle actin (α-SMA) is a protein commonly found in smooth muscle cells, including those in blood vessels and hollow organs such as the intestines and bladder. It is also considered to be expressed by a specialized type of cell called a myofibroblast, which plays a key role in wound healing and tissue repair. In the context of fibrotic scarring, the expression of α-SMA by myofibroblasts is associated with the deposition of excess collagen and the development of scar tissue. Matrixyl Peptide and Tissue Repair One animal study investigated the potential of Matrixyl in promoting wound healing. Animals were divided into seven groups and monitored for 21 days.(9) Results suggested that Matrixyl may positively impact wound healing, with larger potential seen in the high-concentration Matrixyl groups compared to a positive control group. The scientists reported that "the macroscopic results showed that wound healing was improved from 63.5 up to 81.81% in treatment groups compared to that in the negative control group." Another article described the development of a novel conjugate of Matrixyl with imidazolium-based ionic liquid.(10) Imidazolium-based ionic liquids have antimicrobial and skin penetration properties. These conjugates also have collagenesis-inducing activity comparable to the proposed efficacy of Matrixyl. Matrixyl peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Choi, Y. L., Park, E. J., Kim, E., Na, D. H., & Shin, Y. H. (2014). Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS). Biomolecules & therapeutics, 22(4), 321–327. https://doi.org/10.4062/biomolther.2014.053 Errante, F., Ledwoń, P., Latajka, R., Rovero, P., & Papini, A. M. (2020). Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Frontiers in chemistry, 8, 572923. https://doi.org/10.3389/fchem.2020.572923 Jones, R. R., Castelletto, V., Connon, C. J., & Hamley, I. W. (2013). Collagen stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts. Molecular pharmaceutics, 10(3), 1063–1069. https://doi.org/10.1021/mp300549d Tałałaj, U., Uścinowicz, P., Bruzgo, I., Surażyński, A., Zaręba, I., & Markowska, A. (2019). The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity. Molecules (Basel, Switzerland), 24(20), 3698. https://doi.org/10.3390/molecules24203698 Robinson, L. R., Fitzgerald, N. C., Doughty, D. G., Dawes, N. C., Berge, C. A., & Bissett, D. L. (2005). Palmitoyl pentapeptide provides improvement in photoaged human facial skin. International journal of cosmetic science, 27(3), 155–160. https://doi.org/10.1111/j.1467-2494.2005.00261.x Aruan, R. R., Hutabarat, H., Widodo, A. A., Firdiyono, M. T. C. C., Wirawanty, C., & Fransiska, L. (2023). Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow's Feet. The Journal of clinical and aesthetic dermatology, 16(2), 37–43. Kaczvinsky, J. R., Griffiths, C. E., Schnicker, M. S., & Li, J. (2009). Efficacy of anti-aging products for periorbital wrinkles as measured by 3-D imaging. Journal of cosmetic dermatology, 8(3), 228–233. https://doi.org/10.1111/j.1473-2165.2009.00444.x Park H, An E, Cho Lee AR. Effect of Palmitoyl-Pentapeptide (Pal-KTTKS) on Wound Contractile Process in Relation with Connective Tissue Growth Factor and α-Smooth Muscle Actin Expression. Tissue Eng Regen Med. 2017 Jan 19;14(1):73-80. doi: 10.1007/s13770-016-0017-y. PMID: 30603464; PMCID: PMC6171572. Kachooeian, M., Mousivand, Z., Sharifikolouei, E., Shirangi, M., Firoozpour, L., Raoufi, M., & Sharifzadeh, M. (2022). Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing. ACS omega, 7(28), 24695–24704. https://doi.org/10.1021/acsomega.2c02592 Gomes A, Bessa LJ, Fernandes I, Aguiar L, Ferraz R, Monteiro C, Martins MCL, Mateus N, Gameiro P, Teixeira C, Gomes P. Boosting Cosmeceutical Peptides: Coupling Imidazolium-Based Ionic Liquids to Pentapeptide-4 Originates New Leads with Antimicrobial and Collagenesis-Inducing Activities. Microbiol Spectr. 2022 Aug 31;10(4):e0229121. doi: 10.1128/spectrum.02291-21. Epub 2022 Aug 11. PMID: 35950860; PMCID: PMC9431032. 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.
Vesilut (20mg)
Vesilut, aka ED (Glu-Asp) is a synthetic bioregulator peptide, classified amongst the Khavinson peptides. It contains the Glu-Asp sequence which is also found in another Khavinson peptide called Prostamax (Lys-Glu-Asp-Pro). There is a general lack of research on Vesilut, but due to its similarity with Prostamax, it is expected to exhibit similar potential action on tissues such as prostate gland cells and bladder cells. As a bioregulator, aka citomedine, Vasilut is posited to exert these actions via direct interaction with the expression of genes on a cellular level. Chemical Makeup Molecular formula: C9H14N2O7 Molecular weight: 262.2 g/mol Sequence: Glu-Asp Other known titles: alpha-glutamylaspartic acid, ED, SCHEMBL1674753, Vesilute Research and Clinical Studies Due to the lack of any published research that addresses Vesilut’s research potential, we have extracted and presented data from related bioregulators that share the same Glu-Asp sequence. Vesilut and Urinary Bladder Function Urinary bladder function is tightly related to that of surrounding tissues and especially the prostate gland tissues. Swelling of prostate tissues may significantly impede the function of urinary bladder tissues. In the realm of bioregulatory peptides, citomedines with a sequence akin to Vesilut (Glu-Asp), have been suggested to induce intriguing mechanisms of action. This is particularly noted within the context of experimental models of chronic aseptic inflammation in prostate tissues, which commonly translates to swelling and impeded urinary bladder tissue function.(1) Thus, researchers have posited that Vesilut's mechanism may potentially be similar to that of related bioregulators, and may center on modulating key signs of chronic inflammation at the cellular level. One primary action observed in the trials was the reduction in swelling in the experimental prostate tissues.(1) This appeared to have been achieved by influencing the fluid dynamics and cellular responses in the inflamed tissue, leading to a decrease in edema or swelling. Another potential aspect of Vesilut's mechanism, based on the data from related bioregulators, is the attenuation of hyperemia, which refers to an excess of blood in the vessels supplying the prostate gland tissues. This regulation of blood flow may be linked to bioregulator influence on the vascular endothelium and smooth muscle cells, leading to a normalization of blood supply and thus reducing the hyperemic state. Furthermore, bioregulators related to Vesilut appear to exert a potential role in modulating cellular infiltration, an indicator of immune response and inflammation. By potentially regulating the migration and activity of immune cells, these citomedines may potentially support a balance in the inflammatory response, preventing excessive cellular infiltration. A crucial aspect of the aforementioned peptides related to Vesilut is their potential to block the development of sclerotic processes. Sclerosis, the hardening of tissues, is considered to often result from prolonged inflammation, and may lead to the thickening and stiffening of the affected tissue. Thickening and stiffening of prostate tissues may also significantly impact the normal functionality of urinary bladder tissues. Citomedines may intervene in the pathways that lead to the accumulation of fibrous tissues, thereby mitigating the progression of chronic inflammation towards sclerosis. Ultimately, the authors concluded that the exposure of related bioregulator peptides apparently led to “reduced swelling intensity, hyperaemia, and cellular infiltration, blocked the development of sclerosal processes.” (1) Vesilut and Gene Bioregulation The aforementioned potential actions of Vesilut may be related to its hypothetical action on gene expression in tissues. Related peptides that contain the Glu-Asp sequence have been posited to interact with chromosomes and chromatin, possibly leading to the release of genes previously repressed by heterochromatinization. Chromatin is a complex of DNA and proteins found in the nucleus of eukaryotic cells. Its primary function is to package DNA into a smaller volume to fit in the cell, control gene expression, and facilitate DNA replication. Chromosomes are long, thread-like structures made of protein and a single molecule of DNA. They carry genetic information in the form of genes. Ribosomal RNA (rRNA), a key component of ribosomes (the cell's protein factories), is considered to be crucial for translating this genetic code into proteins. The mechanism of peptides with homology to Vesilut may involve alterations in chromatin structure, specifically in aging cells.(2) This alteration might lead to the decondensation of chromatin, as opposed to condensed chromatin which is generally considered to have lower levels of gene activity. By potentially causing decondensation, bioregulator peptides might reactivate certain genes that have been silenced over time due to the natural cell aging process. This reactivation might, in theory, lead to increased protein synthesis and potentially counteract some aspects of cellular aging in various tissues, including prostate gland cells and urinary bladder cells. Thus, the authors posited that “short peptides activate heterochromatin and heterochromatinized regions of cell chromosomes in senile subjects.” Furthermore, bioregulator peptides similar to Vesilut might influence the dynamics of chromosomes by increasing the frequency of sister chromatid exchanges (SCE).(3) SCEs are a natural process where identical sister chromatids exchange genetic material during cell division. An increase in SCE frequency may suggest a role for Vesilut in enhancing chromosomal repair and maintenance mechanisms, potentially contributing to genomic stability in aging cells. Additionally, bioregulator peptides could potentially impact the activity of ribosomal RNA genes, as suggested by an increase in Ag-positive nucleolus organizer regions (NORs). NORs are chromosomal regions that are involved in the formation of ribosomes. An increase in Ag-positive NORs might indicate enhanced production of rRNA, leading to more ribosomes and thus higher protein synthesis capacity. This change may be particularly significant in aging cells, where protein synthesis often decreases. Lastly, the apparent action of bioregulators like Vesilut might involve the reduction of large segments of C-pericentromeric heterochromatin, particularly in specific chromosomes. Heterochromatin is a tightly packed form of DNA, and its decondensation may imply a release of genes previously repressed by such compact structures, leading to potential changes in gene expression profiles in aging cells. Vesilut peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Borovskaya, T. G., Pakhomova, A. V., Vychuzhanina, A. V., Poluektova, M. E., Fomina, T. I., Ermolaeva, L. A., ... & Neplochov, E. A. (2013). Experimental studying of the drug efficiency Prostamax in the therapy of chronic aseptic prostatitis and its complications. Modern Research in Inflammation, 2013. Khavinson VKh, Lezhava TA, Malinin VV. Effects of short peptides on lymphocyte chromatin in senile subjects. Bull Exp Biol Med. 2004 Jan;137(1):78-81. doi: 10.1023/b:bebm.0000024393.40560.05. PMID: 15085253. Dzhokhadze TA, Buadze TZh, Gaĭozishvili MN, Baratashvili NA, Lezhava TA. [Deheterochromatinization of the chromatin in old age induced by oligopeptide bioregulator (Lys-Glu-Asp-Pro)]. Georgian Med News. 2012 Nov;(212):76-82. Russian. PMID: 23221144. 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.
ACE-031 (1mg)
ACE-031 peptide, also known as ActRIIB-IgG1 peptide, appears to be a myostatin inhibitor. In terms of structure, it is a fusion compound consisting of the activin receptor type IIB (ACV2RB) and recombinant immunoglobulin IgG1 FC, which is a form of antibody.(1) Research suggests that this soluble peptide may block the action of circulating myostatin to potentially prevent myostatin from apparently inhibiting the native ACV2RB receptors and thus reducing muscle growth. Myostatin, also known as growth and differentiation factor 8 (GDF8), apparently may be blocked by certain substances termed inhibitors. These inhibitors may target the actions of naturally occurring myostatin, a possible negative regulator of muscle growth primarily found in skeletal muscle tissues. Interestingly, myostatin seemingly has no impact on cardiac or smooth muscle tissues. The discovery of myostatin dates back to 1997, when it was reportedly identified due to its potential inhibitory action on muscle growth, as observed in comparative murine studies.(2) Myostatin may inhibit the activation of murine satellite cells, which are partially committed stem cells within muscle tissue. Additionally, overexpression of myostatin has been suggested to lead to muscle mass reduction in experimental models. Myostatin is thought to bind with the ActR2B receptors with a high affinity, potentially initiating a signaling cascade involving Smad2/3, which is crucial for muscle mass regulation. Other ligands, such as other GDFs and activins, might also bind to ActR2B and potentially regulate muscle growth. These ligands, along with activin receptors, are part of the transforming growth factor-beta (TGF-β) superfamily, which is implicated in controlling tissue growth and differentiation. ACE-031 appears to work by binding with any circulating members from the TGF-β superfamily and, most notably, myostatin. Thus, the ACV2RB receptors in muscle cells remain uninhibited, which is posited to result in the activation of muscle hypertrophy and increase in skeletal muscle tissue size. Besides this, the peptide may have a positive potential for metabolism, fat storage, and bone density. Chemical Makeup Molecular Formula: C3418H5188N928O1062S38 Molecular Weight: 77,489.82 g/mol Other Known Titles: soluble activin type IIB receptor (ActRIIB-IgG1-Fc) Research and Clinical Studies ACE-031 and Muscle Cell Hypertrophy In an experimental setting, which was structured as a double-blind, placebo-controlled research study, the potential of ACE-031 on muscle tissue was investigated, and a pharmacokinetics analysis was conducted.(3) Based on the pharmacokinetic analysis report on ACE-031, the half-life (T(½)) was estimated to be between 10 to 15 days. The apparent outcome of this study indicated a potential increase in muscle mass attributed to a single test with ACE-031. This conclusion is drawn from observations of changes in muscle tissue, which were quantified using specific measurement techniques such as dual-energy X-ray absorptiometry (DEXA) and MRI after 29 days following the exposure of the peptide. The results suggested that there was a noticeable increase in muscle mass. Specifically, a 3.3% increase in total body lean mass and a 5.1% increase in quadriceps femoris muscle volume were noted. More specifically, the researchers commented that “Statistically significant increases in mean total body lean mass (3.3%; P = 0.03, by DXA) and thigh muscle volume (5.1%; P = 0.03, by MRI) were observed at day 29.” These percentages reflect changes in muscle tissue, potentially indicating the hypertrophy-stimulating capability of ACE-031. Additionally, there were apparent shifts in serum biomarkers, suggesting possible improvements in bone and fat metabolism. Moreover, the scientists also concluded that “Statistically significant changes in serum biomarkers suggest ACE-031 also improved bone and fat metabolism.” ACE-031 and Fat Metabolism There may be an increased expression of myostatin in obesity models, according to a review of several scientific studies.(4) For instance, in murine models for studying obesity, the levels of myostatin and its receptor ActR2b appeared to be higher than control models. More specifically, in experimental settings, overexpression of myostatin in murine models appears to correlate with decreased muscle mass, decreased myocardial mass, and increased fat mass. This suggests a potential role of myostatin in promoting fat accumulation and reducing muscle mass. Conversely, depletion of myostatin in certain murine models was linked to a reduction in age-related adipose tissue mass increase and a partial reduction in obesity phenotypes. This suggests that reducing myostatin can mitigate some consequences of obesity. The review also highlights that in mice fed a high-calorie diet, the absence of myostatin appears to result in reduced fat accumulation. This was attributed to two mechanisms: Potential Upregulation of Lipolysis and Fatty Acid Oxidation Enzymes: Myostatin deficiency may increase the expression of enzymes like CPT1a and CPT2, enhancing fatty acid oxidation and reducing lipid accumulation. Apparent Promotion of Brown (Beige) Fat Formation: The lack of myostatin potentially encourages the conversion of white adipose tissue (an energy storage organ) into brown fat, which is involved in thermogenesis and fat burning. Consequently, the researchers employed ACE-031 in control murine models on a high-fat diet, and the peptide appeared to prevent and reduce obesity.(5) ACE-031 and Muscle Contractile Force Continuous research by scientists has suggested that the potential of the peptide may extend beyond myostatin inhibition.(6) By potentially preventing oxidative stress in muscle tissues, the peptide may improve the capacity of the muscle tissue to generate a force and in turn, preserve energy and stimulate the muscles toward oxidative respiration. These observations were made in murine models and measured using magnetic resonance imaging (MR imaging) and dynamic [31P]-magnetic resonance spectroscopy ([31P]-MRS). More specifically, the exposure of ACE-031 was linked to an apparent increase in muscle volume by 33% without altering the distribution of muscle fiber types. This suggests that the peptide may promote muscle growth. Additionally, there was an observed increase in basal oxygen consumption (by 22%) and energy expenditure (by 23%) in the murine models, indicating a potential rise in metabolic activity. During a standardized fatiguing exercise, murine models exposed to ACE-031 showed an apparent muscle performance enhancement. Both maximum and total absolute contractile forces were higher (40% and 24%, respectively) than the control group. However, it is important to note that specific force-generating capacity and fatigue resistance seemed unaffected. ACE-031 did not seem to modify metabolic fluxes, adenosine triphosphate (ATP) homeostasis, or contractile efficiency during exercise. However, it appeared to reduce the intrinsic mitochondrial capacity for ATP production. This aspect may suggest a shift in how muscle cells generate energy, although the implications of this finding are not fully clear. ACE-031 and Bone Density Another study explored the potential impact of ACE-031 on bone tissue in murine models of Duchenne Muscular Dystrophy (DMD), characterized by muscle degeneration and a heightened risk of fractures.(7) The models were divided into groups based on their activity (running or non-running) and additionally into active or placebo groups. The publication suggested that ACE-031 led to an apparent increase in both body and muscle weights in sedentary and exercising murine models. Importantly, femoral micro-CT analysis suggested an increase in bone volume by about 80% and trabecular number by about +70% in the ACE-031 groups. Although running also appeared to improve these bone parameters in the placebo group, it did not appear to enhance trabecular bone structure or volumetric bone mineral density. Additionally, ACE-031 was posited to increase bone mass in vertebral bone tissue, albeit more modestly by about 20-30%. Histological analysis also indicated a potential reduction in osteoclast numbers, and there was data supporting an increased expression of osteoblast marker genes in ACE-031 groups. These findings suggest a potential reduction in bone resorption and an increase in bone formation. Crucially, the researchers commented, "Increased bone mass in femurs translated into enhanced bone strength in biomechanical testing as the maximum force and stiffness were significantly elevated” in the ACE-031 group. ACE-031 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Campbell C, McMillan HJ, Mah JK, Tarnopolsky M, Selby K, McClure T, Wilson DM, Sherman ML, Escolar D, Attie KM. Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Muscle Nerve. 2017 Apr;55(4):458-464. https://pubmed.ncbi.nlm.nih.gov/27462804/ McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997 May 1;387(6628):83-90. https://pubmed.ncbi.nlm.nih.gov/9139826/ Attie KM, Borgstein NG, Yang Y, Condon CH, Wilson DM, Pearsall AE, Kumar R, Willins DA, Seehra JS, Sherman ML. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve. 2013 Mar;47(3):416-23. https://pubmed.ncbi.nlm.nih.gov/23169607/ Yang M, Liu C, Jiang N, Liu Y, Luo S, Li C, Zhao H, Han Y, Chen W, Li L, Xiao L, Sun L. Myostatin: a potential therapeutic target for metabolic syndrome. Front Endocrinol (Lausanne). 2023 May 23;14:1181913. doi: 10.3389/fendo.2023.1181913. PMID: 37288303; PMCID: PMC10242177. Zhang C, McFarlane C, Lokireddy S, Masuda S, Ge X, Gluckman PD, Sharma M, Kambadur R. Inhibition of myostatin protects against diet-induced obesity by enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice. Diabetologia. 2012 Jan;55(1):183-93. doi: 10.1007/s00125-011-2304-4. Epub 2011 Sep 17. Erratum in: Diabetologia. 2015 Mar;58(3):643. PMID: 21927895. Béchir N, Pecchi E, Vilmen C, Le Fur Y, Amthor H, Bernard M, Bendahan D, Giannesini B. ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo. FASEB J. 2016 Oct;30(10):3551-3562. https://pubmed.ncbi.nlm.nih.gov/27416839/ Puolakkainen, Tero et al. “Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy.” BMC musculoskeletal disorders vol. 18,1 20. 19 Jan. 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244551/ 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.