Medicines & Treatments
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.
CJC-1295 (Mod GRF 1-29) & Ipamorelin & GHRP-2 Blend (9mg)
CJC-1295 (Mod GRF 1-29), Ipamorelin, and GHRP-2 are all synthetic peptides that are suggested by research teams to potentially stimulate the release of growth hormone. Anecdotal reports suggest that all three peptides appear synergistic when combined as a blend, potentially providing unique peptide action. CJC-1295 (Mod GRF 1-29) is considered to be an agonist to the receptors for the native Growth Hormone-Releasing Hormone (GHRH). It is an analog of its truncated version called GHRH (1-29) which appears to potentially have the same affinity to the receptors. GHRH 1-29 is potentially the shortest functional sequence of GHRH made up of its initial 29 amino acids. CJC-1295 (Mod GRF 1-29) is a variation that has undergone tetrasubstitution and has been further modified with the addition of a drug affinity complex (DAC) element named N-epsilon-3-maleimidopropionamide. This component may, perhaps, bind to plasma proteins, possibly enhancing the pharmacokinetics of CJC-1295 (Mod GRF 1-29). Ipamorelin is a pentapeptide that apparently mirrors the effects of the natural hunger hormone, ghrelin. This hormone may activate the ghrelin receptors in the pituitary gland, also known as the Growth Hormone Secretagogue receptors (GHS-R1a) which may trigger the release of growth hormone. GHRP-2, also known as Growth Hormone Releasing Peptide 2, is a hexapeptide crafted from six distinct amino acids. It is a synthetic peptide analogous to the receptors of the naturally occurring peptide called ghrelin (aka the GHS-R1a receptors). Thus, GHRP-2 and Ipamorelin peptides appear to trigger GHS-R1a and potentially stimulate the release of growth hormone. However, they may also possibly increase food intake due to their reported effect on ghrelin receptors. This is why they are classified by researchers as Growth Hormone Secretagogues (GHSs). Chemical Makeup (3)(4)(5) Molecular formula: CJC-1295 (Mod GRF 1-29): C152H252N44O42 Ipamorelin: C38H49N9O5 GHRP-2: C45H55N9O6 Molecular weight: CJC-1295 (Mod GRF 1-29): 3367.9 g/mol Ipamorelin: 711.9 g/mol GHRP-2: 817.9 g/mol Other known titles: Ipamorelin Ipamorelin Acetate, IPA GHRP-2 Pralmorelin, Growth hormone-releasing peptide-2 Research and Clinical Studies CJC-1295 (Mod GRF 1-29), Ipamorelin, GHRP-2 Blend and Growth Hormone Deficiencies Numerous clinical studies have been conducted on test subjects exhibiting growth hormone deficiency. These studies are recorded here for educational and research purposes; studies like these are ongoing and do not offer conclusive evidence of the peptide’s potential mechanism of action. In these clinical trials, peptides stimulating growth hormone release appeared to deliver some action in two ways – possibly either via stimulating the pituitary gland to release growth hormones, or possibly acting on the arcuate nucleus of the hypothalamus. While these peptides (including GHRP-2, Ipamorelin, and CJC-1295 (Mod GRF 1-29)) appeared to exhibit high releases of growth hormones, it remains unclear which of the two mechanisms worked. In addition, these studies suggested that these peptides may modulate food intake, cardiac tone, and sleep through apparently specific receptor agonistic action.(4) In another study,(5) six growth hormone-deficient test subjects facing growth failure were presented with growth hormone-stimulating peptides. All subjects were monitored for episodic growth hormone secretion and toxicity levels during this period. For the duration of the study and short while afterwards, It was observed that there appeared to be a gradual rise in the concentration of growth hormones in all subjects. As per V Mericq et al., the studies suggested that the peptides were “well tolerated and […] stimulate GH secretion.” Studies such as this one are still underway, and these peptides require further research. CJC-1295 (Mod GRF 1-29) (Mod GRF 1-29), Ipamorelin, GHRP-2 Blend, and Food Intake In this clinical study,(6) test subjects were presented with GHRP-2 and then presented with unlimited food supply to measure food intake. It was reported that the subjects with peptide presence ate approximately 36% more than the control subjects did. In addition, the growth hormone levels were reportedly increased in these subjects, suggesting the action the peptides had on both food intake and growth hormone levels. As per this study, the growth hormone release-stimulating peptides appeared to be a “valuable tool for investigating the effects on eating behavior.” Research studies are still ongoing to fully explore the potential of peptide blends. Given its potential influence on the ghrelin receptors, Ipamoreline might also potentially enhance appetite and, perhaps, lead to weight gain. One study suggests that Ipamorelin may have possibly contributed to a roughly 15% rise in the body weight of the experimental subjects.(7) Researchers have posited the theory that Ipamorelin might have, to some extent, augmented the fat pad weights in proportion to overall body weight. This may have resulted in a relative increase in body fat as measured by dual energy X-ray absorptiometry (DEXA). Moreover, there is an indication that Ipamorelin might have elevated serum leptin levels, a hormone that is thought to play a role in energy and appetite regulation. Consequently, scientists speculated that the Ipamorelin groups might have experienced an uptick in food consumption leading to an apparent weight gain. Thus, Ipamorelin and GHRP-2 appear may potentially have synergistic effects on increasing hunger levels. On the other hand, CJC-1295 (Mod GRF 1-29) (Mod GRF 1-29) has not been suggested to affect appetite. CJC-1295 (Mod GRF 1-29) (Mod GRF 1-29), Ipamorelin, GHRP-2 Blend, and Bone Mass By apparently increasing growth hormone synthesis, all three peptides may potentially upregulate bone mineral density. Yet, Ipamorelin appears to be the most researched of these three peptides for this focus. In a particular study, murine subjects were either exposed to Ipamorelin or a control agent.(8) The potential effects of Ipamorelin on bone mineral density were monitored in real-time using dual X-ray absorptiometry (DXA) at specific locations, including the femur and L6 vertebrae. After the research duration, the murine subjects' femurs underwent analysis with mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. The findings tentatively indicate that the peptide might have contributed to a potential weight gain and a potential uptick in the overall tibial and vertebral BMC (bone mineral content) as observed via DXA, in contrast to the control set. Yet, when accounting for the weight gain in the total BMC, there seemed to be no notable difference as per the researchers. There might have been a slight increase in the bone mineral density (BMD) of the tibial region, but the overall and vertebral BMDs appeared to stay stable. The pQCT data perhaps suggests that the rise in cortical BMC may be attributed to a growth in the cross-sectional bone area, even though the cortical volumetric BMD seemingly stayed the same. Both the femur and L6 vertebrae volumes might have experienced a growth, but the volumetric BMDs did not appear to shift. These observations hint at the theory that the increase in both cortical and total BMC may potentially stem from improved bone growth leading to expanded bone dimensions, with the volumetric BMD staying consistent. The researchers further suggest that GHRPs may also increase BMC/BMD. CJC-1295 (Mod GRF 1-29) (Mod GRF 1-29), Ipamorelin, GHRP-2 Blend, and Muscle Mass The main focus on CJC-1295 (Mod GRF 1-29) (Mod GRF 1-29) & Ipamorelin & GHRP-2 research has been on the peptides’ potential synergy in regards to increasing muscle mass. Studies on murine models with a GHRH gene deletion (referred to as GHRHKO), hinted that CJC-1295 (Mod GRF 1-29) (Mod GRF 1-29) may potentially have favorable action on lean mass.(9) When influenced by CJC-1295 (Mod GRF 1-29) (Mod GRF 1-29), GHRHKO models appeared to retain typical lean weight and length, unlike the control groups which reportedly struggled to reach standard weight and dimensions. Furthermore, both the comparative lean mass and the underlying fat mass in all groups linked with the peptide seemed to stay consistent with control measurements in normal murine models. This suggests that CJC-1295 (Mod GRF 1-29) (Mod GRF 1-29) might favorably impact muscle and bone structures without necessarily promoting heightened fat accumulation. The researchers also observed a potential uptick in overall pituitary RNA and GH mRNA due to CJC-1295 (Mod GRF 1-29) (Mod GRF 1-29), implying a potential surge in somatotroph cells - the cells in the pituitary gland thought to generate growth hormone. This speculated cell growth was additionally supported by visual evidence from immunohistochemistry. Ipamorelin has also been proposed to increase lean mass, as suggested by the positive nitrogen balance reported in some preliminary studies. In a particular study, researchers sought to explore the potential metabolic effects of Ipamorelin on certain liver markers related to alpha-amino-nitrogen transformation during what might be steroid-induced catabolism. The team attempted to gauge the liver's ability to produce urea-N (CUNS), which could be an indicative measure of nitrogen processing in the liver. They observed potential variations in messenger RNA (mRNA) levels linked with liver urea cycle enzymes, assessed the general nitrogen equilibrium, and speculated on the nitrogen composition of different organs. Researchers suggested that Ipamorelin might have led to an approximate 20% decrease in CUNS in contrast to the catabolic condition potentially brought about by steroids. Moreover, it could have perhaps diminished the activity of urea cycle enzymes, reestablished nitrogen equilibrium, and maybe adjusted or enhanced the nitrogen levels in organs. CJC-1295 (Mod GRF 1-29) (Mod GRF 1-29) & Ipamorelin & GHRP-2 Peptide Blend is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 91976842, CJC1295 Without DAC. https://pubchem.ncbi.nlm.nih.gov/compound/CJC1295-Without-DAC. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 9831659, Ipamorelin. https://pubchem.ncbi.nlm.nih.gov/compound/Ipamorelin. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 6918245, Pralmorelin. https://pubchem.ncbi.nlm.nih.gov/compound/Pralmorelin. Rogério G. Gondo et al, Growth Hormone-Releasing Peptide-2 Stimulates GH Secretion in GH-Deficient Patients with Mutated GH-Releasing Hormone Receptor, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 7, 1 July 2001, Pages 3279–3283, https://doi.org/10.1210/jcem.86.7.7694. Mericq V, Cassorla F, Salazar T, Avila A, Iñiguez G, Bowers CY, Merriam GR. Effects of eight months treatment with graded doses of a growth hormone (GH)-releasing peptide in GH-deficient children. J Clin Endocrinol Metab. 1998 Jul;83(7):2355-60. https://pubmed.ncbi.nlm.nih.gov/9661608/ Laferrère, Blandine et al. “Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.” The Journal of clinical endocrinology and metabolism vol. 90,2 (2005): 611-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824650/ Lall, S., Tung, L. Y., Ohlsson, C., Jansson, J. O., & Dickson, S. L. (2001). Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues. Biochemical and biophysical research communications, 280(1), 132–138. https://doi.org/10.1006/bbrc.2000.4065 Svensson, J., Lall, S., Dickson, S. L., Bengtsson, B. A., Rømer, J., Ahnfelt-Rønne, I., Ohlsson, C., & Jansson, J. O. (2000). The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. The Journal of endocrinology, 165(3), 569–577. https://doi.org/10.1677/joe.0.1650569 Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1290-4. doi: 10.1152/ajpendo.00201.2006. Epub 2006 Jul 5. PMID: 16822960. Aagaard, N. K., Grøfte, T., Greisen, J., Malmlöf, K., Johansen, P. B., Grønbaek, H., Ørskov, H., Tygstrup, N., & Vilstrup, H. (2009). Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 19(5), 426–431. https://doi.org/10.1016/j.ghir.2009.01.001 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.
Pancragen (20mg)
Pancragen is a tetrapeptide with the sequence Lys-Glu-Asp-Trp (KEDW). It is a synthetic structural analog of a peptide isolated from cattle pancreatic cells, which is posited to be a prospective peptide bioregulator for pancreatic function and aging-related metabolic problems. Pancragen has been suggested by researchers to act by penetrating cellular membranes and interacting with the nucleus and nucleolus. This suggests it could influence gene transcription associated with cell differentiation within the pancreatic cells. Key differentiation factors like Ptf1a, Pdx1, Pax6, Foxa2, Nkx2.2, and Pax4 are thought to play essential roles in the proper differentiation of pancreatic cells. Pancragen might up-regulate the expression of these factors, implying a positive action on the maturation of pancreatic cells. Pancragen may also influence the expression of molecules such as MMP2, MMP9, serotonin, CD79alpha, Mcl1, PCNA, and Ki67, suggesting it might boost the functional activity of pancreatic cells. Another mechanism may include a decrease in proapoptotic protein p53 and increase in antiapoptotic protein Mcl1 hinting at an antiapoptotic potential. Last but not least, Pancragen may influence aging biomarkers, reducing caspase-3 and cathepsin B activities and modulating levels of TNF-α and IGF-I. IGF-I, researched for its antiapoptotic actions, suggests that Pancragen's actions might be linked to metabolic correction and antiapoptotic mechanisms. Pancragen also seems to affect the methylation patterns of genes like PDX1, PAX6, and NGN3, which might mediate some of its anti-aging potential on the pancreatic cells. Chemical Makeup Molecular formula: C26H36N6O9 Molecular weight: 576.25 g/mol Sequence: Lys-Glu-Asp-Trp Other known titles: KEDW, DWa (amidate) Research and Clinical Studies In the information below, we have broken down the latest clinical and preclinical research on Pancragen’s potential as observed in various experimental models. Pancragen and the Pancreas The tetrapeptide Pancragen has been studied for its potential impact on pancreatic cells, particularly in relation to cell differentiation and the regulation of insulin and glucagon release, crucial elements in the pancreatic cells’ endocrine function. (1) Research posited that Pancragen might penetrate cellular membranes to interact with the nucleus and nucleolus, thereby possibly influencing the transcription of genes crucial for cellular differentiation within the pancreatic gland. Key differentiation factors such as Ptf1a, Pdx1, Pax6, Foxa2, Nkx2.2, and Pax4 are crucial for the proper functioning and differentiation of various pancreatic cell types. It is posited that Pancragen's interaction may potentially up-regulate the expression of these factors, which may play a role in the cellular maturation process of both acinar and islet cells in the pancreatic gland. The experiments conducted on embryonic cultures of pancreatic acinar cells in this study suggested that Pancragen might significantly enhance the expression of Ptf1a and Pdx1 proteins, which are known to be crucial for the maturation of acinar and islet cells. The study suggested that Pancragen's actions might be more pronounced in aged cultures, where an apparent decrease in the expression of these proteins is observed as a part of the cellular aging process. This potential up-regulation of key differentiation factors by Pancragen is posited to possibly lead to an increased differentiation of pancreatic cells, and, subsequently, may aid in restoring the functional activity of the pancreatic cells to a state akin to that observed in younger cell cultures. The researchers also posited that “transcription factors that regulate differentiation of pancreatic cells are a pharmacological target for Pancragen, which allows considering it as an effective tool in the treatment of diabetes mellitus and pancreatitis.” Another research study using murine models to gauge the impact of Pancragen on the pancreas's functional morphology, also yielded interesting findings.(2) Initially, when DM was induced in murine models, there was a noted decrease in insulin-producing B cells and an uptick in glucagon-producing A cells. Such changes point to disrupted pancreatic cell functionality. However, upon exposure to Pancragen, potentially encouraging shifts were observed. Murine models showed evident compensatory changes in pancreatic cells and tissue. Specifically, Pancragen seemed to bolster insulin production from B cells while tempering glucagon production from A cells. Additionally, the proliferative activity of certain cells and their apoptosis seemed to normalize, closely resembling control murine models. Further research has also suggested that Pancragen might play a pivotal role in the modulation of various cellular markers and proteins associated with the vitality of pancreatic cells. When applied to aging pancreatic cells, there was an observed increase in the expression of matrix metalloproteinase MMP2 and MMP9, serotonin, glycoprotein CD79alpha, the antiapoptotic protein Mcl1, and proliferation markers PCNA and Ki67. Conversely, there was a decrease in the expression of the proapoptotic protein p53 in aged pancreatic cell cultures. From these observations, it can be posited that the tetrapeptide potentially holds the capability to activate the expression of signaling molecules that serve as markers of the functional activity of pancreatic cells.(3) Pancragen and Metabolic Problems Studies have delved into the potential of Pancragen on metabolic problems in aged test subjects. For example, in one study, the focus was mainly on carbohydrate metabolism and the potential role Pancragen may play in regulating it.(4) The introduction of Pancragen was observed to significantly lower fasting glucose levels during a standard glucose tolerance test, alongside a reduction in insulin concentrations and the insulin resistance index. This suggests a potential utility of Pancragen in addressing the disturbances in carbohydrate metabolism, especially given the observed persistence of its glucose-lowering action post-exposure. It is critical to note that the study was focused on august test subjects, and the scope of Pancragen’s potential may be contingent on several other variables, including the severity of insulin resistance and other factors. The researchers also commented that “Administration of the tetrapeptide Pancragen is a promising approach to the correction of insulin resistance in elderly.” Another study aimed to investigate the potential impact of Pancragen on the endocrine function of the pancreatic cells and the metabolic status of test models.(5) Aged test models used in this research were used to understand the potential of Pancragen in addressing age-related dysfunctions in the overall metabolism as well as the pancreatic islet apparatus. In older test models, there was a noted reduced rate of glucose utilization compared to younger counterparts. Moreover, higher insulin and C-peptide peaks were observed 5 and 15 minutes post-glucose introduction. However, when Pancragen was introduced per test model daily over 10 days, there was a marked improvement in the glucose utilization rate. This intervention also seemed to normalize the dynamics of plasma insulin and C-peptide in response to glucose. Intriguingly, the actions of Pancragen lingered, with some aspects of metabolic status and pancreatic cell function remaining improved even three weeks after the cessation of the trial. In a study examining the actions of Pancragen on endothelial function within the setting of chronic hyperglycemia using murine models, it was observed that the introduction of Pancragen may have potential role in restoring endothelial adhesive characteristics. (6) Restoring these endothelial adhesive characteristics is crucial because, in models of metabolic problems, proper endothelial function plays a vital role in blood flow regulation and preventing complications such as atherosclerosis. Deficiencies or abnormalities in endothelial adhesion may increase susceptibility to vascular damage, making this restoration a key target for averting it. Pancragen and Aging Pancragen has been posited as a possible bioregulator for adjusting metabolic problems associated with aging. To understand Pancragen's impact on aging, a study examined its potential on murine models across different age groups.(7) There was a noted decrease in certain aging biomarkers like caspase-3 and cathepsin B activities when Pancragen was introduced to the younger murine models. Interestingly, in the mature murine models, Pancragen application resulted in a significant reduction of TNF-α levels and an elevation in IGF-I, both of which are critical indicators related to aging and metabolic processes. The study also delved into a rapid experimental aging model by inducing diabetes mellitus in murine models. It was observed that Pancragen potentially normalized blood glucose levels, emphasizing its previously identified hypoglycemic properties. Furthermore, the presence of Pancragen might have suppressed certain apoptotic enzymatic components in the pancreatic cells, suggesting that its biological actions may be associated with both metabolic correction and antiapoptotic mechanisms. The actions of Pancragen on natural biological aging are potentially realized at the IGF-I level, known for its "survival factor" antiapoptotic actions. Moreover, the tetrapeptide's potential interaction with certain genes suggests that its influence might extend to the proteolytic processing level. According to another trial, Pancragen has been posited to tissue-specifically influence gene expression in pancreatic cell cultures.(8) The study suggests that variations in the methylation patterns of the PDX1, PAX6, and NGN3 gene promoter regions in pancreatic cells may be associated with aging and could potentially be the cause behind the alterations in their expression levels. This implies that long-standing changes in gene expression upon aging might be driven by modifications in these promoter methylation patterns. However, the expression levels of the PAX4 and FOXA2 genes in pancreatic cells seem to deviate during aging and in response to Pancragen, even when the methylation patterns of the PAX4 gene remain stable. Curiously, the FOXA2 gene's promoter region in pancreatic cells exhibited only a handful of methylated CpG sites, with their methylation levels being influenced by both cell culture aging and Pancragen. Yet, this did not correlate straightforwardly with changes in gene expression levels. This suggests that, despite the influence of Pancragen on certain gene methylation patterns, the exact relationship between methylation and gene expression may be intricate and possibly regulated by other, yet unidentified, mechanisms. Pancragen peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Khavinson, V. K.h, Durnova, A. O., Polyakova, V. O., Tolibova, G. H., Linkova, N. S., Kvetnoy, I. M., Kvetnaia, T. V., & Tarnovskaya, S. I. (2013). Effects of pancragen on the differentiation of pancreatic cells during their ageing. Bulletin of experimental biology and medicine, 154(4), 501–504. https://doi.org/10.1007/s10517-013-1987-6 Kvetnoi, I. M., Ryzhak, A. P., Kostyuchek, I. N., & Tafeev, Y. A. (2007). Effect of tetrapeptide pancragene on functional morphology of the pancreas in rats with experimental diabetes mellitus. Bulletin of experimental biology and medicine, 143(3), 368–371. https://doi.org/10.1007/s10517-007-0114-y Khavinson, V. K.h, Sevost'ianova, N. N., Durnova, A. O., Lin'kova, N. S., Tarnovskaia, S. I., Dudkov, A. V., & Kvetnaia, T. V. (2012). Advances in gerontology = Uspekhi gerontologii, 25(4), 680–684. Korkushko, O. V., Khavinson, V. K.h, Shatilo, V. B., Antonyk-Sheglova, I. A., & Bondarenko, E. V. (2011). Prospects of using pancragen for correction of metabolic disorders in elderly people. Bulletin of experimental biology and medicine, 151(4), 454–456. https://doi.org/10.1007/s10517-011-1354-4 Goncharova, N. D., Ivanova, L. G., Oganyan, T. E., Vengerin, A. A., & Khavinson, V. K. (2015). Advances in gerontology = Uspekhi gerontologii, 28(3), 579–585. Khavinson, V. K.h, Gavrisheva, N. A., Malinin, V. V., Chefu, S. G., & Trofimov, E. L. (2007). Effect of pancragen on blood glucose level, capillary permeability and adhesion in rats with experimental diabetes mellitus. Bulletin of experimental biology and medicine, 144(4), 559–562. https://doi.org/10.1007/s10517-007-0377-3 Khavinson, V. K.h, Gapparov, M. M., Sharanova, N. E., Vasilyev, A. V., & Ryzhak, G. A. (2010). Study of biological activity of Lys-Glu-Asp-Trp-NH2 endogenous tetrapeptide. Bulletin of experimental biology and medicine, 149(3), 351–353. https://doi.org/10.1007/s10517-010-0944-x Ashapkin, V. V., Linkova, N. S., Khavinson, V. K.h, & Vanyushin, B. F. (2015). Epigenetic mechanisms of peptidergic regulation of gene expression during aging of human cells. Biochemistry. Biokhimiia, 80(3), 310–322. https://doi.org/10.1134/S0006297915030062 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.
Vesugen (20mg)
Vesugen, aka KED, is a bioregulator peptide and identified within the group of peptides isolated and synthesized by Russian scientist, Vladimir Khavinson. It is a tripeptide derived from a sequence of amino acids related to vascular wall proteins, encapsulating the amino acids lysine, glutamic acid, and aspartic acid. Vesugen is primarily known for its potential influence on vascular endothelial cells. Further, its potential extends to a wide array of biological processes, making it a viable research compound within the context of anti-aging and neuroprotection research. Primarily, Vesugen is recognized for its potential vasoprotective impacts, with a particular emphasis on its role in the maintenance and repair of vascular endothelial cells. These cells form the lining of blood vessels. In addition to its vascular implications, Vesugen has also been explored for its neuroprotective and geroprotective consequences. Studies have examined its effects on neuron survival and morphology, suggesting its possible role in combating neurodegenerative diseases and enhancing neuroplasticity. Chemical Makeup Molecular formula: C15H26N4O8 Molecular weight: 390.39 g/mol Sequence: Lys-Glu-Asp Other known titles: KED, lysyl glutamyl aspartic acid, SCHEMBL3767701 Vesugen Research and Clinical Studies The information provided below synthesizes the latest insights from early-stage research regarding the capabilities of Vesugen, as demonstrated through a variety of experimental approaches. Vesugen and Vasoprotective Potential Vasugen may have vasoprotective potential, particularly relevant in the context of aging and vascular function. This potential is primarily attributed to its proposed ability to influence the behavior of vascular endothelial cells. The available research posits that Vesugen may exert vasoprotective action through the modulation of cell proliferation.(1) It is thought to do this by potentially regulating the expression of the Ki-67 protein, a marker that is closely associated with cellular proliferation. This protein's expression seemingly decreases as part of the natural aging process, affecting the vascular endothelium's ability to renew itself. Vesugen is hypothesized to interact with the promoter regions of the Ki-67 gene, potentially leading to increased expression of this protein. The possible impact of Vesugen on vascular endothelial cells includes the stimulation of cell proliferation. By potentially enhancing the expression of Ki-67, Vesugen might contribute to the maintenance or restoration of the integrity and function of the vascular endothelium. This may be particularly relevant in addressing age-related vascular function problems, including issues such as reduced proliferative capacity and the increasing prevalence of polyploid cells, which may contribute to vascular lesions and atherosclerosis. Moreover, the study suggests that Vesugen might interact with DNA at specific sites, influencing gene expression in a way that may favor vascular function. This interaction is thought to occur mainly in the minor groove of DNA, with Vesugen forming hydrogen bonds with specific DNA base pairs. Ultimately, the researchers concluded that the “vasoprotective effect of peptide vesugen ... could be realized through epigenetic regulation of Ki-67 gene expression.” The presumed mechanism underlying its potential effects of Vesugen may involve the epigenetic regulation of genes thought to code for proteins that serve as markers of endothelial functional activity, crucial in cardiovascular function. In vitro investigations into Vesugen's impact on endothelial cells, particularly those impacted by atherosclerosis and restenosis, suggest that it may help normalize the expression of endothelin-1.(2) This molecule's expression typically rises in atherosclerotic and restenotic conditions, suggesting that Vesugen could possibly play a role in addressing these pathologies. Moreover, Vesugen appears to potentially aid in restoring cellular interactions, possibly through its influence on connexin expression. Connexins are vital for cell-to-cell communication, which is essential for maintaining endothelial integrity and function. An additional aspect of Vesugen's potential action is its apparent geroprotective effect, potentially achieved by increasing the expression of sirtuin1, a protein involved in DNA repair. This increase in sirtuin1 expression might be significant for cardiovascular function, as it may contribute to the mitigation of damage at the genetic level. Vesugen and Neuroprotective Potential Investigation into Vesugen’s neuroprotective potential within the context of neurodegeneration has elaborated on the apparent impact of the peptide on neuroplasticity and neuron morphology in murine models simulating certain neurodegeneration conditions.(3) A key aspect of this research was the examination of long-term potentiation (LTP) in the hippocampus, a crucial area for memory and learning. The neurodegenerated murine models showed a trend toward impaired neuroplasticity compared to wild-type murine models, particularly after high-frequency stimulation of Schaffer’s collaterals. However, this observed impairment in neuroplasticity was not statistically significant, suggesting only a subtle action. The exposure to the Vesugen peptide in these murine models suggested a potential to restore LTP, suggesting a role in enhancing neuroplasticity. Despite this positive suggestion, the action of the Vesugen peptide on restoring LTP also did not reach statistical significance, leaving its impact as a promising yet unconfirmed hypothesis. Furthermore, the study delved into the action of Vesugen peptide on neuron morphology, specifically focusing on the dendritic spine density in the CA1 region of the hippocampus. This area is vital for synaptic connections and is notably affected in neurodegeneration. The research found that the introduction of the Vesugen peptide helped prevent the elimination of postsynaptic structures in CA1 neurons of the neurodegeneration murine models. Interestingly, the most pronounced action of Vesugen was observed in the restoration of mushroom and thin spines, which are critical for synaptic strength and memory. This finding aligns with literature data on spine balancing in neurodegeneration progression, suggesting a modulatory action of Vesugen on spine morphology. Moreover, the study noted sex-related differences in the neuroprotective action of Vesugen peptide in neurodegeneration murine models. In male models, Vesugen peptide significantly increased dendritic spine density and restored mushroom spine numbers, suggesting a gender-specific response in neuroprotective action. The authors commented that the neuroprotective potential of Vesugen and similar peptides is “defined by their ability to prevent dendritic spine elimination and neuroplasticity impairments at the molecular epigenetic level.” Another trial aimed to investigate the mechanisms behind the potential of Vesugen in addressing neurodegenerative conditions.(4) The primary focus was on its influence on gene expression and protein synthesis, which are crucial in processes like apoptosis, aging, neurogenesis, and, more specifically, neurodegeneration. Experimental findings, coupled with published reports, suggest that Vesugen may play a role in regulating the expression of genes associated with cell aging and apoptosis, such as р16 and р21. These genes are pivotal in determining the lifespan of cells and their programmed death, which are critical factors in neurodegenerative diseases. Moreover, Vesugen appears to affect genes and proteins that are involved in neuronal differentiation, such as NES (Nestin) and GAP43. Nestin is a type of intermediate filament protein potentially involved in the structural support of cells, particularly in the early stages of development in the nervous system. GAP43, on the other hand, is a protein that may play a key role in axonal growth during neural development and in the regeneration of neurons. The modulation of these genes and proteins by Vesugen might be integral in fostering neurogenesis, a process that may be beneficial in countering neurodegenerative processes. Furthermore, the peptide seems to interact with genes implicated in the pathogenesis of neurodegeneration. These include SUMO, APOE, and IGF1. SUMOylation, a post-translational modification involving the SUMO protein, is known to be involved in a variety of cellular processes, including transcriptional regulation, DNA repair, and protein stability – all of which are critical in the context of neurodegeneration. APOE, or apolipoprotein E, has been extensively studied for its role in lipid metabolism and its significant association with neurodegenerative diseases. Lastly, IGF1, or Insulin-like Growth Factor 1, is a hormone crucial for brain development and is thought to have neuroprotective properties. Vesugen and Geroprotective Potential Vesugen may potentially influence the behavior of prostatic fibroblasts, particularly concerning the expression of certain differentiation factors. This potential was observed in contexts where these cells exhibited signs of aging, suggested by reduced expression of differentiation markers in late-passage cultures.(5) Specifically, Vesugen is posited to stimulate the expression of CXCL12 and WEGC1 in these prostatic fibroblasts. CXCL12, also known as stromal cell-derived factor 1 (SDF-1), is a chemokine, a type of signaling protein. It is primarily indentified for its potential in the immune system, where it may aid in the regulation of immune cell movement. CXCL12 may also be involved in other biological processes, such as hematopoiesis (the formation of blood cellular components) and angiogenesis (the formation of new blood vessels). Its significance in cellular signaling may extend to influencing cell migration and activation, although the full scope of its actions and interactions in various tissues is still a subject of ongoing research. WEGC1, on the other hand, is less extensively studied, and its role is not as clearly defined in the literature. It might be involved in cellular differentiation processes, particularly in specific types of cells like fibroblasts. The exact functions of WEGC1, including how it influences cell behavior and interacts with other cellular components, are areas that require more detailed exploration. Its identification in studies concerning cellular aging and differentiation, such as those involving Vesugen, suggests that it could have a role in these processes, but the extent and nature of this role are yet to be fully elucidated. Most notably, the potential of Vesugen seemed to be more pronounced in aged cultures. This suggests, albeit with a degree of uncertainty, that Vesugen might exhibit geroprotective action, potentially supporting the maintenance or rejuvenation of cellular functions that decline with age. Clinical research has also aimed to explore Vesugen's potential in modifying biological age markers, a key aspect of aging, and thus its geroprotective potential.(6) Vesugen reportedly exhibited a notable anabolic effect, which is linked to improved activity in the central nervous system and other vital organs. This action was associated with a potential slowing of the aging process according to biological age indicators. An interesting aspect of the study was the observation of prooxidant activity through chemiluminescence. This suggests that Vesugen may induce some oxidative processes. Additionally, there was a reported decrease in CD34+ positive hematopoietic polypotent cells in the blood, suggesting a potential inhibition of hemopoiesis. This finding suggests these cells might not be actively involved in adaptive reactions during the appreciation of Vesugen. Vesugen peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Khavinson, V. K.h, Tarnovskaia, S. I., Lin'kova, N. S., Guton, E. O., & Elashkina, E. V. (2014). Advances in gerontology = Uspekhi gerontologii, 27(1), 108–114. Kozlov KL, Bolotov II, Linkova NS, Drobintseva AO, Khavinson VK, Dyakonov MM, Kozina LS. [Molecular aspects of vasoprotective peptide KED activity during atherosclerosis and restenosis]. Adv Gerontol. 2016;29(4):646-650. Russian. PMID: 28539025. Khavinson V, Ilina A, Kraskovskaya N, Linkova N, Kolchina N, Mironova E, Erofeev A, Petukhov M. Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease. Pharmaceuticals (Basel). 2021 May 27;14(6):515. doi: 10.3390/ph14060515. PMID: 34071923; PMCID: PMC8227791. Khavinson VK, Lin'kova NS, Umnov RS. Peptide KED: Molecular-Genetic Aspects of Neurogenesis Regulation in Alzheimer's Disease. Bull Exp Biol Med. 2021 May;171(2):190-193. doi: 10.1007/s10517-021-05192-6. Epub 2021 Jun 26. PMID: 34173097. Khavinson VKh, Linkova NS, Polyakova VO, Kheifets OV, Tarnovskaya SI, Kvetnoy IM. Peptides tissue-specifically stimulate cell differentiation during their aging. Bull Exp Biol Med. 2012 May;153(1):148-51. doi: 10.1007/s10517-012-1664-1. PMID: 22808515. Meshchaninov VN, Tkachenko EL, Zharkov SV, Gavrilov IV, Katyreva IuE. [EFFECT OF SYNTHETIC PEPTIDES ON AGING OF PATIENTS WITH CHRONIC POLYMORBIDITY AND ORGANIC BRAIN SYNDROME OF THE CENTRAL NERVOUS SYSTEM IN REMISSION]. Adv Gerontol. 2015;28(1):62-7. Russian. PMID: 26390612. 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.
Lipopeptide (200mg)
Lipopeptide, characterized by the sequence Palmitoyl-Gly-Gln-Pro-Arg, is a palmitoylated fragment derived from immunoglobulin G (IgG). IgG is a type of antibody, considered a crucial component of the immune system that apparently mediates various inflammatory processes. The palmitoylation of this peptide fragment, which involves the attachment of a palmitic acid molecule, may also enhance its experimental potential. This modification appears to improve the lipopeptide's ability to penetrate through the corneal layers of skin tissue models. The increased penetration appears to be due to the added lipid (fat) component, which aids in traversing the lipid-rich environment of the outer layers of skin tissue. Chemical Makeup Molecular formula: C38H68N6O8 Molecular weight: 736.9 g/mol Sequence: Pal-Gly-Gln-Pro-Arg Other known titles: Pal-GQPR, Palmitoyl Tetrapeptide-7/3 Research and Clinical Studies The summary below reflects the latest findings from preliminary studies on the functionalities of Lipopeptide, as revealed through diverse experimental methods. Lipopeptide and the Extracellular Dermal Matrix One study conducted a series of evaluations on a blend of peptides including Lipopeptide (Pal-GQPR) for their potential action on skin cell structure.(1) Echography tests suggested that this blend might reduce the thickness of the subepidermal low-echogenic band and support its density, indicating a possible improvement in skin structure. Moreover, studies in murine models hinted that these peptides might potentially enhance the extracellular dermal matrix structure compared to a placebo. More specifically it was posited that this compound might also play a role in decreasing the secretion of interleukin-6 (IL-6), a cytokine involved in inflammatory responses. IL-6 is a molecule that is typically associated with immune responses and appears to be elevated during inflammation, potentially contributing to various inflammatory skin conditions. The possible reduction of IL-6 secretion by Lipopeptide suggests that it may aid in mitigating inflammation, especially following UVB radiation exposure, a common cause of skin cell inflammation and damage. Additionally, Lipopeptide is thought to potentially stimulate the production of critical structural components around skin cells, such as laminin IV and V, as well as collagen VII. Laminins, particularly types IV and V, are integral components of the basement membrane, a layer that supports epithelial cells and is considered essential for tissue integrity. They play a crucial role in cell adhesion, differentiation, and migration, which are vital for skin repair and maintenance. Collagen VII, on the other hand, is a key component of anchoring fibrils that provide structural support and stability to the skin. It is essential for the attachment of the epidermis to the underlying dermis. The stimulation of these components by Lipopeptide may imply a potential role in enhancing the skin's structural framework.(2) Other researchers have also commented that Lipopeptide may have an action “as an anti-inflammatory agent and has anti-aging and skin firming [potential].”(3) Lipopeptide and Photoaged Skin Cells The potential of Lipopeptide was investigated in a randomized controlled trial (RCT) as a blend alongside other peptides and active ingredients. This peptide, along with other compounds, such as retinyl palmitate and natural extracts, was assessed for its potential in improving the appearance of photoaged skin cells. Twelve days into the experiment, the peptide was observed to have stimulated the deposition of fibrillin-1 in the skin, a marker for skin repair, compared to the baseline levels. This was comparable to the apparent results observed with all-trans retinoic acid (RA), considered to be a clinical standard for photoaged skin cells. The accumulation of fibrillin-1 indicates a potential structural change in the skin, although this alone does not confirm the success of the experiment. In a 6-month RCT the peptide appeared to potentiate an improvement in skin wrinkles compared to the baseline. Interestingly, this potential improvement became more pronounced after 12 months. The vehicle formulation, which lacked the active ingredients, did not show similar results, suggesting that the ingredients in the test product, including Lipopeptide, may contribute to the observed effects. Furthermore, the study investigated the distribution of fibrillin-1 in skin biopsies from the RCT. Skin applied with the Lipopeptide appeared to have a significant increase in fibrillin-1 in the papillary dermis compared to the placebo group. This supports the idea that long-term experiments with Lipopeptide may lead to a visible improvement in the photoaged skin. The researchers concluded that Lipopeptide may “produce significant improvement in the appearance of wrinkles and further supports the [study] of fibrillin-1 as a robust biomarker for the repair of photoaged dermis.”(4) Lipopeptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Mondon, P., Hillion, M., Peschard, O., Andre, N., Marchand, T., Doridot, E., Feuilloley, M. G., Pionneau, C., & Chardonnet, S. (2015). Evaluation of dermal extracellular matrix and epidermal-dermal junction modifications using matrix-assisted laser desorption/ionization mass spectrometric imaging, in vivo reflectance confocal microscopy, echography, and histology: effect of age and peptide applications. Journal of cosmetic dermatology, 14(2), 152–160. https://doi.org/10.1111/jocd.12135 Resende, D. I. S. P., Ferreira, M. S., Sousa-Lobo, J. M., Sousa, E., & Almeida, I. F. (2021). Usage of Synthetic Peptides in Cosmetics for Sensitive Skin. Pharmaceuticals (Basel, Switzerland), 14(8), 702. https://doi.org/10.3390/ph14080702 Fadilah, N. I. M., Rahman, M. B. A., Yusof, L. M., Mustapha, N. M., & Ahmad, H. (2021). The Therapeutic Effect and In Vivo Assessment of Palmitoyl-GDPH on the Wound Healing Process. Pharmaceutics, 13(2), 193. https://doi.org/10.3390/pharmaceutics13020193 Watson, R. E., Ogden, S., Cotterell, L. F., Bowden, J. J., Bastrilles, J. Y., Long, S. P., & Griffiths, C. E. (2009). Effects of a cosmetic 'anti-ageing' product improves photoaged skin [corrected]. The British journal of dermatology, 161(2), 419–426. https://doi.org/10.1111/j.1365-2133.2009.09216.x Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
PEG-MGF (5mg)
MGF is an acronym for Mechano Growth Factor, a research peptide that scientists consider to belong to the class of IGF-1 (insulin-like growth factor) family.(1) An isoform of IGF-1, MGF is also known as IGF-1Ec, and is believed to primarily be produced in the liver.(2) The IGF-1 gene appears to undergo transcription and may generate the three mRNA isoforms: IGF-1Ea, IGF-1Eb, and IGF-1Ec. This indicates that MGF (or IGF-1Ec) may be identical to IGF-1 but with a different E domain. Synthesis of each isoform appears to possess specific functions in different tissues as a response to diverse stimuli. PEG-MGF, or polyethylene glycol (PEG)-ylated MGF, is a synthetic form of MGF. Pegylation connects polyethylene glycol (PEG) to another compound to alter its structure. Scientists consider that MGF by itself may have a short half-life; however, once bound with PEG, the half-life may be extended by some days. Research studies posit that PEG IGF-1 may be more impactful than recombinant IGF-1 for muscle cell regeneration and improving muscle function. The main reasoning was attributed to the hypothesis that PEG may not easily bind with any other compounds, and may thereby lead to delayed clearance. In addition, modifying the C terminus of IGF-1 with the addition of PEG may increase the peptide's potential impact on tissues.(3) Overview Researchers suggested the existence of three IGF-1 precursor proteins formed upon the splicing of the mature IGF-1. Each precursor comprises 70 amino acid residues from the mature IGF-1, and may only differ in the amino acid sequence attached to the COOH terminal, possibly determining its function. During the late 1990s and early 2000s, it was suggested that one of the three precursors, IGF-1EC (MGF), may increase upon muscle injury.(4) Several studies have been carried out thereafter(3) to isolate and synthesize the (PEG)-ylated MGF to modify and potentially improve the impact and action of the peptide. The studies have suggested that under muscle stress the mature IGF-1 may become spliced as a response to stress and may thereby produce and release one of the isoforms called IGF-1EC, also known as Mechano Growth Factor (MGF).(4) One research hypothesis suggests that as MGF increases, the amino acid sequence attached to the COOH terminal of MGF may become activated and promote cell proliferation in muscle stem cells. Further studies indicated that PEG-MGF may stimulate the proliferation of C2C12 muscle cells and myoblasts upon presentation. Based on these results, it was suggested that the MGF peptide may be biologically active and inert by nature. PEG-MGF may induce stronger, more durable action of normal MGF. Chemical Makeup Molecular Formula: C121H200N42O39 Molecular Weight: N/A Other Known Titles: PEG-MGF-E, PEG-MGF-Ct24E Research and Clinical Studies PEG-MGF Peptide and Muscle Structure Muscle resistance activity seems to activate mechano-growth factor (MGF) mRNA in muscle tissues, which researchers suggest manifests as a substantial 163% rise from baseline levels.(5) This pronounced increase suggests a potentially direct response of MGF to mechanical stimuli within the muscles. Concurrently, an observed surge in growth hormone levels, which typically accompanies muscle resistance, may add complexity to this molecular interplay. Data suggests a 456% augmentation in MGF mRNA coinciding with resistance activities, whereas an increase in growth hormone levels alone appears to influence MGF mRNA expression by about 80% compared to baseline. The scientists commented “This may reflect an overall up-regulation of transcription of the IGF-I gene prior to splicing.” Consequently, it is hypothesized that MGF may play a critical role in the organism’s intrinsic mechanism to mitigate muscle damage and promote tissue repair in response to mechanical stress. This hypothesis underscores the intricate and coordinated molecular responses triggered by physical exertion, reflecting a sophisticated biological adaptation to preserve muscle integrity and function. To further investigate this, a study(6) was conducted to examine the potential of MGF on muscle repair and wound healing. Experimental murine models induced with muscle contusion and muscular macrophage depletion were used as study subjects. Based on comprehensive analyses following the study, the researchers theorized that MGF might induce muscular repair in the wounded tissues. MGF appeared to decline the rate of fibrosis in the contused muscles and reduced the expressions of inflammatory cytokines, chemokines, and stress factors. Preliminary analyses indicated that MGF might affect fibrosis in damaged muscle tissue through the likely suppression of collagen types I and III expression. These collagens are considered essential components of the extracellular matrix involved in fibrotic processes. Additionally, there appeared to be a noticeable decrease in oxidative stress markers and matrix metalloproteinases (MMPs), which might suggest that MGF may attenuate certain inflammatory processes associated with muscle injury. Moreover, the prevalence of contused muscles seemed to decrease, potentially facilitating the repair mechanisms in the injured tissues. The investigation also proposed that MGF's influence on the functional dynamics of satellite cells post-injury and immune cell presence at the injury site—both deemed critical to muscle regeneration—might be minimal. This proposition is based on the stable expression levels of MyoD and myogenin, which are considered to be pivotal markers of satellite cell proliferation and differentiation, respectively. Therefore, while MGF may alleviate some facets of the muscle injury response, its direct impact on satellite cell functionality in these specific circumstances may not definitively be established. The study further suggested that MGF might modify the inflammatory environment within the injured muscle tissue. This modulation is tentatively evidenced by a reported decrease in the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-1 beta (IL-1β), and transforming growth factor-beta (TGF-β), alongside chemokines like CCL2, CCL5, and CXCR4 following MGF experimentation. Additionally, there was a speculative indication that MGF might help mitigate oxidative stress in injured muscles, as suggested by a possible reduction in the expression of gp91phox, an element of NADPH oxidase that appears to play a significant role in the generation of reactive oxygen species. PEG-MGF Peptide and Cardioprotection The main goal of this study(7) was to evaluate the potential of MGF action on cardiac muscles undergoing programmed cell death following hypoxia, a condition characterized by limited supply of oxygen. Rats were experimentally induced with hypoxia with only 1% oxygen supply, leading to cellular apoptosis. Once the peptide was given to the rat models, the study reported that the peptide appeared to induce increased migration of stem cells to the heart, possibly leading to apoptosis inhibition. More specifically, MGF is suggested to potentially enhance the migration of mesenchymal stem cells (hMSCs). This process suggests a chemotactic action, which may be strategically employed to guide stem cells to areas affected by injury or disease. The basis for this proposition stems from apparent increases in the levels of the Bcl-2 gene, which is believed to play a critical role in enhancing cell survival, thus suggesting that MGF may possess qualities that inhibit apoptotic processes in cells. This observation underscores the possibility of MGF as a potential agent in enhancing tissue regeneration by modulating cellular mechanisms that may prevent programmed cell death. PEG-MGF Peptide and Bone Fracture The main goal of this study(8) was to evaluate the potential of MGF on bone injury. 27 rabbits were experimentally induced with a 5-mm bone defect and were then divided into three groups that were given MGF, or a control substance for 5 consecutive days. Post-trial, when the bone tissues were histologically examined, the researchers reported that the control tissue appeared to be the least healed, whereas the bone tissue with MGF appeared to be the most healed. Comparatively, MGF-exposed tissues also exhibited a superior healing process relative to those exposed to Insulin-like Growth Factor 1 (IGF-1), suggesting that MGF may interact with cellular processes in a distinct manner from IGF-1. Further insights from the study suggest that MGF might influence the cell cycle by potentially halting it at specific stages, and it may also activate the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase 1/2 (MAPK-Erk1/2) signaling pathway. These mechanisms indicate that MGF might employ a multifaceted strategy to enhance cell proliferation, which likely involves altering cell cycle progression and triggering particular molecular pathways crucial for cellular repair and regeneration. This nuanced approach underscores MGF's potentially complex and targeted action in bone healing models. PEG-MGF Peptide and Neuroprotection Several studies(9) were conducted on mice who were experimented on in order to increase the levels of MGF and thereby study the action of increased MGF concentration on their brain cells. One study included the breeding of mice to constitutively overproduce MGF in the hippocampus area of the brain. The hippocampus is considered primarily responsible for regulating the neurogenesis phenomenon in the body. This overproduction of MGF appeared to result in high concentrations of BrdU, a biological marker representative of proliferative action. Another study was conducted where mice were bred to conditional MGF production at 1, 3, and 12 months old. Behavioral analysis and biological responses were examined after 2 years. These mice were reported to exhibit elevated levels of BrdU and neurogenesis. MGF Peptide and Muscle Tissue Hypertrophy The main aim of one pivotal study on MGF(10) was to assess its potential on muscle cells of varying ages. In this study, muscle cell cultures, from neonatal to aged stages, underwent evaluation after being exposed to MGF. It was observed that in younger cells, MGF seemed to postpone the onset of cellular senescence, which is the gradual deterioration of cellular function. This delay suggests that MGF might be able to maintain muscle function and its regenerative properties, which typically decline with age. Additionally, the study noted an enhancement in cell proliferation among cells ranging from neonatal to young; however, such proliferation did not appear to extend to the older aged cells. In these older cells, there was a noticeable increase in muscle hypertrophy, characterized by an augmented muscle cell size. Yet, there was a marked reduction in the number of reserve cells. These reserve cells, which typically do not immediately differentiate or amalgamate into myotubes, were apparently at a reduced proportion in the culture. Myotubes, crucial structures in muscle development, are formed through the fusion of muscle cells. This fusion process was apparently enhanced across all age groups by MGF, which not only increased the myotube size but potentially also the muscle’s functional capabilities through the augmented expression of muscle-specific contractile proteins. This observation is significant as it implicates a reduced presence of reserve cells, suggesting that MGF might encourage these cells to participate more actively in muscle formation. In conclusion, the researchers posited that “MGF-24aa-E peptide alone has a marked ability to enhance satellite cell activation, proliferation and fusion for muscle repair and maintenance.” PEG-MGF is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Philippou A, Papageorgiou E, Bogdanis G, Halapas A, Sourla A, Maridaki M, Pissimissis N, Koutsilieris M. Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro. In Vivo. 2009 Jul-Aug;23(4):567-75. https://pubmed.ncbi.nlm.nih.gov/19567392/ Zabłocka, B., Goldspink, P. H., Goldspink, G., & Górecki, D. C. (2012). Mechano-Growth Factor: an important cog or a loose screw in the repair machinery? Frontiers in endocrinology, 3, 131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485521/ Janssen, J. A., Hofland, L. J., Strasburger, C. J., van den Dungen, E. S., & Thevis, M. (2016). Potency of Full-Length MGF to Induce Maximal Activation of the IGF-I R Is Similar to Recombinant Human IGF-I at High Equimolar Concentrations. PloS one, 11(3), e0150453. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798685/ Rotwein P. (2014). Editorial: the fall of mechanogrowth factor?. Molecular endocrinology (Baltimore, Md.), 28(2), 155–156. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896639/ Hameed M, Lange KH, Andersen JL, Schjerling P, Kjaer M, Harridge SD, Goldspink G. The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men. J Physiol. 2004 Feb 15;555(Pt 1):231-40. doi: 10.1113/jphysiol.2003.051722. Epub 2003 Oct 17. PMID: 14565994; PMCID: PMC1664832. Liu X, Zeng Z, Zhao L, Chen P, Xiao W. Impaired Skeletal Muscle Regeneration Induced by Macrophage Depletion Could Be Partly Ameliorated by MGF Injection. Front Physiol. 2019 May 17;10:601. https://pubmed.ncbi.nlm.nih.gov/31164836/ Doroudian G, Pinney J, Ayala P, Los T, Desai TA, Russell B. Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes. Biomed Microdevices. 2014 Oct;16(5):705-15. https://pubmed.ncbi.nlm.nih.gov/24908137/ Deng M, Zhang B, Wang K, Liu F, Xiao H, Zhao J, Liu P, Li Y, Lin F, Wang Y. Mechano growth factor E peptide promotes osteoblasts proliferation and bone-defect healing in rabbits. Int Orthop. 2011 Jul;35(7):1099-106. https://pubmed.ncbi.nlm.nih.gov/21057789/ Alec Walker. Hearts and Minds of Mice and Men: Mechano Growth Factor a new tool in the battle against age-related neuron loss? 20 Jul 2017. Kandalla PK, Goldspink G, Butler-Browne G, Mouly V. Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages. Mech Ageing Dev. 2011 Apr. https://pubmed.ncbi.nlm.nih.gov/21354439/ Dr. MarinovDr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.
GHK-Cu (200mg)
GHK-Cu is a naturally occurring complex molecule composed of a tripeptide called GHK (made up of glycine, histidine, and lysine amino acids) bound to a copper ion. The copper ion appears to stabilize and deliver GHK to cells. Research suggests that GHK-Cu may play a potentially essential role in restoring damaged tissues, wound repair, and may support immune response. These hypotheses have sprung from it’s perceived potential to stimulate the production of collagen, elastin, and glycosaminoglycans, crucial intercellular matrix components. In addition to its potential on the intercellular matrix, GHK-Cu may also have antioxidant and anti-inflammatory characteristics that may protect cells from damage caused by free radicals. Chemical Makeup Molecular Formula: C14H23CuN6O4 Molecular Weight: 340.38 g/mol Other Known Titles: Cu-GHK, Copper tripeptide-1, 6BJQ43T1I9 Research and Clinical Studies GHK-Cu and Collagen Synthesis Studies suggest that GHK-Cu may stimulate collagen synthesis and induce in situ tissue recovery. The researchers suggest that these actions may be due to “the presence of a GHK triplet in the alpha 2(I) chain of type I collagen”.(1) More specifically, the tripeptide sequence composed of glycine, histidine, and lysine, abbreviated as Gly-His-Lys, may be derived during the breakdown of collagen through hydrolysis. This breakdown is typically associated with the disintegration of collagen fibers, frequently resulting from either tissue damage or the natural degradation process. It is proposed that this specific peptide sequence may have a significant impact on cellular communication processes, specifically targeting fibroblasts. Fibroblasts are specialized cells deemed essential in producing new collagen fibers, vital components for structural support in various tissues. The interaction between the Gly-His-Lys peptide and fibroblasts is believed to potentially initiate a cascade of biological events leading to the synthesis of collagen, thereby playing a potential role in the mechanisms of tissue repair and regeneration. This process of collagen synthesis by fibroblasts may be critical to contribute to the overall restoration and healing of damaged tissues. One study, lasted a month, reported that GHK-Cu might stimulate type 1 collagen production in clinical settings.(2) The scientists compared the potential of GHK-Cu to other peptides and vitamin C and vitamin A derivatives on photodamaged skin. The research primarily investigated the potential action of the peptide on dermal procollagen synthesis, keratinocyte proliferation, differentiation, and cutaneous inflammation. The peptide appeared to improve all indicators, and the researchers reported an apparent increase in skin thickness, elasticity, and hydration. Another study explored the potential interaction between GHK-Cu and hyaluronic acid (HA) on collagen synthesis, particularly focusing on their potential collaborative actions in dermal fibroblasts and an ex-vivo skin model.(3) HA is portrayed as a significant component of skin cells, noted for its moisture-binding potential and actions on cell proliferation and inflammation, with different molecular weights (LMW and HMW) showing distinct biological activities. The experimental setup involved exposure of dermal fibroblasts with various combinations of GHK-Cu and HA, measuring the synthesis of collagen types I, IV, and VII. It was suggested that certain combinations, particularly at a GHK-Cu to LMW HA ratio of 1:9, appeared to have significantly boosted the synthesis of collagen IV—more so than when either compound was studied independently. This suggests a potential synergistic action between GHK-Cu and HA, specifically in enhancing collagen IV levels. The synergy might arise from the combined action of GHK-Cu in stimulating glycosaminoglycan production, promoting collagen synthesis, and HA's role in reducing collagen degradation by scavenging reactive oxygen species and inhibiting matrix metalloproteinases. The research highlights that the molecular weight of HA and the ratio of GHK-Cu to HA may be crucial in maximizing this action, with optimal results observed at specific ratios. Further studies employing an ex-vivo skin model supported these findings, suggesting a notable increase in collagen IV synthesis at the dermal-epidermal junction when exposed to the optimized GHK-Cu and LMW HA mixture. This action was visually corroborated through increased fluorescence intensity in immunofluorescence assays, indicating higher collagen IV content. GHK-Cu and Wound Infection Both animal and clinical studies have hypothesized that GHK-Cu may reduce inflammation and the risk of infection in wounds. One murine study investigated the potential of GHK-Cu on ischemic open wounds.(4) The researchers reported, "On days 6, 10, and 13, tripeptide-copper complex-treated wounds contained significantly lower concentrations of TNF-alpha and MMP-2 and MMP-9 than control wounds.” Tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in systemic inflammation, along with matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) — enzymes that break down extracellular matrix proteins — might potentially influence both the inflammatory processes and the remodeling of tissues. This suggests that GHK-Cu, a copper complex recognized for its healing capacities, might have a role in reducing inflammation and preventing tissue breakdown in models of ischemic wounds, where blood flow restriction potentially causes tissue damage. A clinical trial that involved GHK-Cu in addition to standard wound care also reported an apparently reduced risk of infection compared to standard processes alone.(5) The study was conducted on models of diabetic neuropathic ulcers, and the rate of infections was only 7% in the GHK-Cu models compared to 34% in the control models. GHK-Cu and Wound Healing Studies in rabbits report that GHK-Cu has been tested regarding its potential in wound healing and laser exposure at different intensities.(6) The results were compared to control wounds without intervention. Wounds were observed daily, and biopsies were taken weekly for four weeks to evaluate the inflammation rate and neovascularization. The GHK-Cu and high-intensity laser groups appeared to have a shorter average time for healing and greater neutrophil and vessel counts. There was an apparently shorter median time for the first observable granulation tissue and an apparently faster filling of an open wound with granulation tissue compared to the control group. Granular tissue is composed of newly formed connective tissue and minuscule blood vessels that appear on wound surfaces as part of the healing process. It is suggested that there might be a link between the emergence of this tissue and heightened activity of antioxidant enzymes. These enzymes are proteins that assist in shielding cells from the harmful action of oxidative stress, a process where cell components are damaged due to the presence of unstable molecules known as free radicals. Furthermore, there is a potential enhancement in vascular development observed in these scenarios. This vascular development is considered vital for transporting essential nutrients and oxygen to the damaged area, thereby facilitating the repair of tissue. The previously mentioned study on rats with open ischemic wounds also reported an apparent decrease in wound area of the GHK-Cu group that was greater compared to the control group on days 3 to 5, 6 to 9, and 11 to 13.(4) Similarly, the clinical study on models of diabetic neuropathic ulcers reported that GHK-Cu, combined with standard wound care, appeared more impactful for wound closure than standard care alone.(5) The apparent closure rate was three times faster than standard care. The researchers also suggested that “The enhancement of wound closure was more pronounced (median of 89.2% compared with -10.3% for vehicle; p < 0.01) in larger (greater than 100 mm(2) initial area at study entry) plantar ulcers caused by the failure of this size of ulcer to respond adequately to standardized wound care.” In research involving both standard murine models and those adapted to mimic diabetic conditions, wound dressings composed of collagen and infused with GHK were observed to potentially enhance wound healing.(7) The observations suggest that by the conclusion of the third week, wounds exposed to dressings containing biotinylated GHK (a tripeptide with skin regenerative properties) nearly achieved full closure, registering at 99.39%. This is potentially a significant enhancement compared to the 69.49% closure rate observed with control dressings lacking this modification. Further analysis indicated that the wounds exposed to GHK might have shown elevated levels of glutathione and ascorbic acid. These are considered critical antioxidants for their potential roles in facilitating tissue repair by protecting cells from oxidative stress. There was also a tentative observation of increased epithelialization, a process essential for the regeneration of the skin's outer layer, in these experimental conditions. Apart from the enhanced activity of fibroblasts, which are pivotal in collagen synthesis, tissue repair, and regeneration, there was also noted a potential rise in mast cell activation. Mast cells are important for mediating inflammatory responses, which are deemed crucial during the initial phases of wound healing. GHK-Cu and Active Radicals Photodamage of tissues such as the skin involves the formation of reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive carbonyl species (RCS), which may induce damage to proteins, DNA, and lipids. Studies suggest that the amino acid sequence in GHK-Cu may have anti-RCS potential against radicals such as 4-hydroxynoneal, acrolein, malondialdehyde, and others.(8) Furthermore, it may potentially prevent protein glycation. Moreover, researchers have suggested that GHK-Cu may have potential action in reducing iron release from ferritin. Ferritin is a lipid peroxidation catalyst, and GHK-Cu may help to reduce the formation of iron complexes in damaged tissues and thus decrease inflammation. One study suggested an 87% decrease in iron release with the help of GHK-Cu to lower oxidation in damaged tissues.(9) GHK-Cu may also reduce the production of reactive oxygen species and inflammatory cytokines while increasing the activity of antioxidant enzymes. This was proposed by an animal study investigating the potential of GHK-Cu on lipopolysaccharide-induced lung inflammation in mice.(10) The peptide was suggested to suppress the activation of NF-κB and p38 MAPK signaling pathways associated with inflammation. This might potentially lead to reduced infiltration of inflammatory cells in the lungs of mice with lung damage and lower levels of TNF-1 and IL-6 production to minimize damage. Further studies also suggest that the amino-acid sequence of GHK-Cu may have an antioxidative potential on ROS, such as hydroxyl radicals, and it may be even stronger than generic antioxidative peptides.(12) GHK-Cu and Wrinkles in Skin Tissue Models GHK-Cu has been suggested to host potential for improving experimental models of disturbed skin topography, such as wrinkles and fine lines. One study posited that a GHK-Cu possibly reduces visible bioindicators, improving skin laxity, and clarity. The peptide apparently also reduced the depth of wrinkles while potentially increasing skin density and thickness after 12 weeks of experimentation in skin cell models with varying degrees of photodamage.(13) Another investigation focused on the actions of GHK-Cu compared to a control compound and vitamin K. Over a period of 12 weeks, the GHK-Cu ostensibly performed better than the controls in reducing epidermal wrinkles. The peptide may also have increased skin density and thickness.(14) In a separate 12-week study in mild to advanced photodamage, GHK-Cu seemingly improved skin attributes such as laxity, clarity, and firmness. This peptide was also associated with a reduction in coarse wrinkles, and mottled pigmentation. Additionally, the peptide apparently stimulated dermal keratinocyte proliferation, as evidenced by histological analysis of biopsies.(15) GHK-Cu peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References Maquart, F. X., Pickart, L., Laurent, M., Gillery, P., Monboisse, J. C., & Borel, J. P. (1988). Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS letters, 238(2), 343–346. https://doi.org/10.1016/0014-5793(88)80509-x Abdulghani, A. A., Sherr, A., Shirin, S., Solodkina, G., Tapia, E. M., Wolf, B., & Gottlieb, A. B. (1998). Effects of creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin-A pilot clinical, histologic, and ultrastructural study. Disease Management and Clinical Outcomes, 4(1), 136-141. Jiang F, Wu Y, Liu Z, Hong M, Huang Y. Synergy of GHK-Cu and hyaluronic acid on collagen IV upregulation via fibroblast and ex-vivo skin tests. J Cosmet Dermatol. 2023 Sep;22(9):2598-2604. doi: 10.1111/jocd.15763. Epub 2023 Apr 16. PMID: 37062921. Canapp, S. O., Jr, Farese, J. P., Schultz, G. S., Gowda, S., Ishak, A. M., Swaim, S. F., Vangilder, J., Lee-Ambrose, L., & Martin, F. G. (2003). The effect of tripeptide-copper complex on healing of ischemic open wounds. Veterinary surgery : VS, 32(6), 515–523. https://doi.org/10.1111/j.1532-950x.2003.00515.x Mulder, G. D., Patt, L. M., Sanders, L., Rosenstock, J., Altman, M. I., Hanley, M. E., & Duncan, G. W. (1994). Enhanced healing of ulcers in patients with diabetes by treatment with glycyl-l-histidyl-l-lysine copper. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 2(4), 259–269. https://doi.org/10.1046/j.1524-475X.1994.20406.x Gul, N. Y., Topal, A., Cangul, I. T., & Yanik, K. (2008). The effects of tripeptide copper complex and helium-neon laser on wound healing in rabbits. Veterinary dermatology, 19(1), 7–14. https://doi.org/10.1111/j.1365-3164.2007.00647.x Alven, S., Peter, S., Mbese, Z., & Aderibigbe, B. A. (2022). Polymer-Based Wound Dressing Materials Loaded with Bioactive Agents: Potential Materials for the Treatment of Diabetic Wounds. Polymers, 14(4), 724. https://doi.org/10.3390/polym14040724 Cebrián, J., Messeguer, A., Facino, R. M., & García Antón, J. M. (2005). New anti-RNS and -RCS products for cosmetic treatment. International journal of cosmetic science, 27(5), 271–278. https://doi.org/10.1111/j.1467-2494.2005.00279.x Miller, D. M., DeSilva, D., Pickart, L., & Aust, S. D. (1990). Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation. Advances in experimental medicine and biology, 264, 79–84. https://doi.org/10.1007/978-1-4684-5730-8_11 Park, J. R., Lee, H., Kim, S. I., & Yang, S. R. (2016). The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget, 7(36), 58405–58417. https://doi.org/10.18632/oncotarget.11168 Zhang, Q., Yan, L., Lu, J., & Zhou, X. (2022). Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway. Frontiers in molecular biosciences, 9, 925700. https://doi.org/10.3389/fmolb.2022.925700 Sakuma, S., Ishimura, M., Yuba, Y., Itoh, Y., & Fujimoto, Y. (2018). The peptide glycyl-ʟ-histidyl-ʟ-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals. International journal of physiology, pathophysiology and pharmacology, 10(3), 132–138. Leyden J., Stephens T., Finkey M., Appa Y., Barkovic S. Skin care benefits of copper peptide containing facial cream. Proceedings of the American Academy of Dermatology Meeting; February 2002; New York, NY, USA. Leyden J., Stephens T., Finkey M., Barkovic S. Skin Care Benefits of Copper Peptide Containing Eye Creams. University of Pennsylvania; 2002. Finkley M., Appa Y., Bhandarkar S. Copper peptide and skin. In: Elsner P., Maibach H., editors. Cosmeceuticals and Active Cosmetics: Drugs vs. Cosmetics. New York, NY, USA: Marcel Dekker; 2005. pp. 549–563. 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.
Adipotide (FTPP) (10mg)
Adipotide Peptide, also known as FTPP (Fat-Targeted Proapoptotic Peptide), fat-targeted proapoptotic peptide, or proapoptotic peptide, has been widely researched and is posited by scientists to be a proapoptotic peptide that may contribute to cell apoptosis. Adipotide may possibly act as a peptide targeting prohibitin, which is why it also bears the name Prohibitin-targeting peptide 1 (Prohibitin-TP01). Current research is still exploring Adipotide’s potential in this area and its potential actions related to its targeting properties.(1) Prohibitins are natural proteins considered by scientists to regulate such functions as cell formation, metabolism, and inflammation. Research teams initially considered Adipotide for its supposed potential to mitigate the action of cancer cells. Still, the peptide indicated it may have research potential for experiments investigating lipolysis and obesity mitigation, leaving the research pioneers “at a loss of words.”(2) It was presumed that Adipotide might prevent blood supply to the cancer cells, resulting in cell death and malignant cell growth inhibition. Upon further research, it was suggested by the scientists that the peptide appeared to exhibit the same mechanism of action but on fat cells instead. This “proof of concept” study was an early-stage experiment suggesting that the peptide may have significant potential. Yet, the compound has to be studied further to understand its full potential and impact on cells. Overview Researchers isolated a naturally occurring peptide (sequence CKGGRAKDC) via phage display methodology and combined it with a proapoptotic sequence, forming the now-termed Adipotide compound. Adipotide is homologous to the peptide sequence found in the white adipose tissue. Owing to this development and characteristics, researchers suggest that the peptide may possibly target the prohibitin PHB1 found at the surface of the adipose tissue – possibly attaching and thereby damaging them, potentially causing a blood supply disruption to the adipocytes (fat cells).(1) Prohibitins are considered by scientists to act as a vascular marker of the fatty tissues, and Adipotide may possibly be able to identify these markers and consequently conduct apoptosis on these cells.(3) Further, researchers speculate that Adipotide may interact not only with prohibitin but also another receptor called annexin A2 (ANX2) and thus potentially disrupt their role in supporting blood and fat supply to fat cells in white adipose tissue. Studies suggest that prohibitin and ANX2, when interacting in a complex with a fatty acid transporter called CD36, potentially facilitate the uptake of fatty acids by the endothelium and their subsequent transport into adipocytes. One study suggested that there was a purported white adipose tissue hypotrophy in murine models lacking ANX2, despite apparently normal white adipose tissue vascularization, adipogenesis, and glucose metabolism. This condition was potentially attributed to reduced fatty acid uptake by white adipose tissue endothelium and adipocytes. It was suggested that the efficiency of fatty acid transport relies on the interaction of ANX2 and prohibitin. This interaction was posited to be essential for mediating fatty acid transport from the endothelium into adipocytes. Additionally, it was commented that ANX2 and prohibitin form a complex with CD36, and this interaction is crucial for fatty acid transport. Importantly, the colocalization of prohibitin and CD36 on the adipocyte surface was induced by extracellular fatty acids, suggesting a dynamic regulation of this protein complex in response to fatty acid levels. The study posited that the biochemical interaction between ANX2 and prohibitin potentially regulates CD36-mediated fatty acid transport in white adipose tissue, unveiling a potential pathway that compounds like Adipotide might target.(4) Consequently, Adipotide is posited to potentially burn the fat stored in these fat cells as fuel, according to researchers' speculations.(2) Based on early preclinical studies on monkeys, it was also suggested that following Adipotide presentation, the monkeys exhibited apparently reduced insulin resistance.(5) Chemical Makeup Molecular Formula: C152H252N44O42 Molecular Weight: 2611.41 g/mol Other Known Titles: FTPP Research and Clinical Studies Adipotide (FTPP) Initial Research Adipotide's mode of action appears to hinge on its selective affinity for the receptor prohibitin, expressed on the surface of endothelial cells in the vasculature of white adipose tissue. The compound's potential to cause targeted apoptosis is facilitated by its fusion to the d-enantiomer D(KLAKLAK)2 sequence, an amphipathic peptidomimetic posited to disrupt mitochondrial membranes upon internalization into cells. This disruption might lead to cell death, specifically in the targeted vasculature. To evaluate the compound's potential, Adipotide was presented to three different types of primate models daily for four weeks. No deliberate changes were made to their diet or exercise routine. After the study, it was suggested by the researchers that the models apparently lost about 11% of weight and 39% of the fat deposits in their bodies compared to baseline.(5) As suggested by the authors, some of the models also exhibited apparent mild renal dysfunction, as reported across four study groups, A, B, C, and D. Creatinine levels apparently increased in study groups A and B, however, after a washout period, these returned to optimal levels. Further, the authors suggested that there may be an apparent reduction in food intake in the test models, which raises questions about potential actions on appetite or satiety signals, which could be another avenue through which Adipotide may exert its potential. However, the specific mechanisms by which Adipotide might influence these processes, if at all, are still unclear. While Adipotide is suggested to have potential at the cellular level for inducing weight loss by targeting the vasculature of white adipose tissue, its exact mechanisms of action, particularly in relation to appetite regulation and metabolic changes, require further investigation to fully understand its potential implications in the context of obesity. Adipotide (FTPP) and Malignant Cells Scientists surveyed a number of blood vessels and tissues (both normal and malignant), and isolated and studied the various peptides and molecules distributed in them. Peptides, proteins, and certain molecular distributions are considered to be specific and differentially expressed in normal and cancer tissues under control conditions. Through various chemical isolation and analytical techniques, researchers posited four native ligand receptors that appeared to be specific to certain types of carcinogenic cells. These receptors may, in turn, be vascular markets, and the researchers suggested that Adipotide exerts some of its potential action via these receptors. Notably, the research suggested four native ligand-receptors within the cells comprising the vasculature, two apparently common across multiple tissues and two potentially specific to certain tissues. The researchers posited common ligand-receptors were integrin α4/annexin A4 and cathepsin B/apolipoprotein E3. These were suggested following identification through protein purification, identification of native ligands from protein arrays, and supervised online database searches.(6) Adipotide (FTPP) and Diabetes In preliminary studies, obese murine models were given Adipotide to explore its potential mechanism on adipose cells. The research team noted it that within 2 to 3 days of the experiment, the murine models appeared to exhibit improved glucose tolerance and decreased levels of triglycerides.(7) More specifically, the study was conducted on obese murine models, and the alterations in glucose tolerance and metabolic variables were apparently observed without a corresponding change in body weight. This observation suggests a mechanism independent of weight loss. In the context of glucose homeostasis, Adipotide apparently improved glucose tolerance as suggested by a reduction in insulin and triglycerides, which was not merely a consequence of reduced food intake, as the changes differed from those in control groups with similar food intake. As noted, the apparent improvement in glucose tolerance was rapid, suggesting a potential direct influence of Adipotide on glucose regulatory mechanisms. Microarray analysis suggested shifts in gene expression within the white adipose tissue of Adipotide-presented murine models. Notably, pathways related to mitochondrial function, oxidative phosphorylation, and amino acid degradation appeared to be altered by the high-fat diet but were seemingly reversed by Adipotide. This suggests a potential role for Adipotide in modulating mitochondrial activity and metabolic processing in white adipose tissue, possibly contributing to improved glucose regulation. The study also explored the potential impact of Adipotide on various metabolic variables. While increased serum lipids were expected due to rapid white adipose tissue reduction, the findings were somewhat different. Triglycerides decreased in Adipotide-presented murine models, and there were distinctive levels of fatty acids and acylcarnitines compared to control groups. These observations hint at potential metabolic alterations not solely related to food intake or body weight changes. Another aspect examined was the serum levels of adipokines like adiponectin and resistin, which are considered to influence glucose regulation. The data did not suggest significant changes in these markers attributable to Adipotide, and the authors posited that the rapid improvement in glucose homeostasis might not be directly linked to these adipokines. Furthermore, Adipotide appeared to cause unique changes in serum acylcarnitines, indicating potential alterations in the mitochondrial metabolism of fatty acids and amino acids. Specifically, there was suggested to be a decrease in short- and medium-chain acylcarnitines and an increase in long-chain species, implying a shift in the metabolic processing of these molecules.(7) Adipotide peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Thuaud, F., Ribeiro, N., Nebigil, C. G., & Désaubry, L. (2013). Prohibitin ligands in cell death and survival: mode of action and therapeutic potential. Chemistry & biology, 20(3), 316–331. https://doi.org/10.1016/j.chembiol.2013.02.006 Melissa H., Cancer treatment shows promise for rapid weight loss, Los Angeles Times, 10 Nov 2011. https://www.latimes.com/local/la-xpm-2011-nov-10-la-he-drug-fat-loss-20111110-story.html Kolonin, Mikhail G et al. “Reversal of obesity by targeted ablation of adipose tissue.” Nature medicine vol. 10,6 (2004): 625-32. https://pubmed.ncbi.nlm.nih.gov/15133506/ Salameh A, Daquinag AC, Staquicini DI, An Z, Hajjar KA, Pasqualini R, Arap W, Kolonin MG. Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue. JCI Insight. 2016 Jul 7;1(10):e86351. doi: 10.1172/jci.insight.86351. PMID: 27468426; PMCID: PMC4959783. Barnhart, Kirstin F et al. “A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.” Science translational medicine vol. 3,108 (2011): 108ra112. doi:10.1126/scitranslmed.3002621. https://pubmed.ncbi.nlm.nih.gov/22072637/ Staquicini, Fernanda I et al. “Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients.” Proceedings of the National Academy of Sciences of the United States of America vol. 108,46 (2011): 18637-42. doi:10.1073/pnas.1114503108. https://pubmed.ncbi.nlm.nih.gov/22049339/ Kim, Dong-Hoon et al. “Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium.” Diabetes vol. 61,9 (2012): 2299-310. doi:10.2337/db11-1579. https://pubmed.ncbi.nlm.nih.gov/22733798/ Kolonin, Mikhail G et al. “Reversal of obesity by targeted ablation of adipose tissue.” Nature medicine vol. 10,6 (2004): 625-32. doi:10.1038/nm1048. https://pubmed.ncbi.nlm.nih.gov/15133506/ 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.