Peptides
Pal-GHK (200mg)
Palmitoyl-GHK, also known as palmitoyl-tripeptide-1, is a synthetic hybrid molecule consisting of a chain of three amino acids attached to a palmitic acid molecule. The GHK sequence, which consists of the amino acids Gly-His-Lys, is found naturally in plasma, discovered in 1973 by Pickart et al.(1) The addition of palmitoyl to the molecule is thought to result in better penetration through the stratum corneum of the epidermal barrier.(2) The palmitoyl group, which is a fatty acid chain, is thought to increase lipophilicity, which may potentially enhance the compatibility of the molecule with the lipid-rich environment of the stratum corneum. The added palmitoyl group might also act as a penetration enhancer by disrupting the tightly packed lipid structure of the stratum corneum. This disruption could temporarily loosen the lipid matrix, allowing Pal-GHK and other agents to permeate through various skin tissue models. Researchers have suggested that Pal-GHK may stimulate collagen production, a key component of the skin's extracellular matrix (ECM). This hypothesis was initially developed because the Gly-His-Lys sequence is also a structural fragment of the protein collagen. Gly-His-Lys is believed to be released during collagen hydrolysis, typically induced in tissue repair and to mitigate inflammation. Therefore, the tripeptide is believed to act as a natural feedback signal to fibroblasts, the cells responsible for producing collagen and other ECM components. Pal-GHK may also exhibit antioxidant potential against damage caused by free radicals. Free radicals are unstable molecules that may damage cell structures and are considered to contribute to the aging process. By potentially neutralizing free radicals, Palmitoyl-GHK may reduce cellular aging and inflammation. Chemical Makeup Molecular formula: C30H54N6O5 Molecular weight: 578.8 g/mol Other Known Titles: Palmitoyl Tripeptide-1, Palmitoyl oligopeptide, Biopeptide-CL Research and Clinical Studies Pal-GHK and Collagen Synthesis Research by Maquart et al. dating back to 1988 and published in the journal FEBS Letters suggests that the Gly-His-Lys in Pal-GHK is a fragment produced during the hydrolysis of collagen.(3) Such fragments are produced when collagen is damaged, and they may signal fibroblasts to initiate the process of collagen synthesis. Pal-GHK may have a similar potential to stimulate collagen, elastin, and glycosaminoglycans, important components of the extracellular matrix of the skin. The researchers concluded, "The presence of a GHK triplet in the alpha 2(I) chain of type I collagen suggests that the tripeptide might be liberated by proteases at the site of a wound and exert in situ healing effects." A placebo-controlled clinical study suggests that Pal-GHK may stimulate collagen synthesis, as concluded following the assessment of the apparent effect of the peptide on skin thickness. The trial involved twenty-three subjects, and the researchers reported a small but statistically significant increase in skin thickness of about 4% compared to the placebo.(5) Pal-GHK and Wrinkle Depth A clinical study was conducted to ascertain the peptide’s potential in reducing the depth and length of wrinkles along the stratum corneum. The study evaluated the action of the peptide in a cream form (6) and included fifteen subjects. The scientists reported an apparent reduction in wrinkle length, depth, and texture inconsistency (roughness) following the study period. Another clinical experiment involved a combination of Pal-GHK tripeptide and another palmitoylated peptide called Pal-GQPR.(7) Pal-GQPR is a tetrapeptide with the sequence of Pal-Gly-Gln-Pro-Arg, and it is a fragment of immunoglobulin G (IgG) which is considered to play an important role in reducing the amount of interleukin 6 (IL6) production. The design was a blind, randomized clinical study that included twenty-eight subjects. There was an apparent reduction of wrinkle depth, volume, density, texture inconsistency, and the area occupied by deep wrinkles following exposure to the combination of the two palmitoylated peptides. Pal-GHK and Antioxidation A 2018 laboratory experiment by Sakuma et al. suggested that the amino-acid sequence of Pal-GHK may have antioxidative potential.(8) The researchers also reported that this potential was apparently more powerful than other compounds classified as antioxidative and commonly used in research, such as carnosine and reduced glutathione. More specifically, the researchers shared that "Experiments utilizing an ESR spin-trapping technique revealed that, among hydroxyl (·OH), superoxide (O2-·), and peroxyl (ROO·) radicals generated by respective chemical reaction systems, GHK diminished signals of both ·OH and ROO·." Active radicals appear to be apparent mediators of photodamage. Examples of such active radicals include reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive carbonyl species (RCS), which are considered to cause harm to lipids, DNA, and proteins. Studies have suggested that the amino acid sequence found in Pal-GHK may potentially prevent protein glycation and may possess anti-RCS properties against various radicals like acrolein, malondialdehyde, and 4-hydroxynoneal.(9) Additionally, Pal-GHK has been suggested to have the potential to reduce the release of iron from ferritin, which catalyzes lipid peroxidation. In other words, Pal-GHK may lead to a lower rate of lipid peroxidation, ostensibly preserving the integrity of cell membranes and reducing cellular damage. In the context of skin tissue integrity, this might contribute to enhanced skin cell function and survival. One study shared results of an apparent 87% decrease in the iron release from damaged tissue using Pal-GHK, which appeared to have reduced oxidation in the affected tissues.(10) By potentially lowering lipid peroxidation, Pal-GHK might indirectly help mitigate the alteration of DNA and proteins, potentially reducing risk factors that may otherwise lead to cellular damage. Pal-GHK may also potentially reduce the production of reactive oxygen species and inflammatory cytokines while increasing the activity of antioxidant enzymes. During one experiment using a murine model, Pal-GHK was suggested to suppress the activation of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways, both of which are associated with inflammation.(11) Pal-GHK might potentially inhibit the activation of p38 MAPK either by blocking the upstream kinases that activate it or by interfering with the signaling molecules that initiate its phosphorylation. The inhibition may conceivably suppress the inflammatory response, reducing the overall stress on cells. This may lead to reduced infiltration of inflammatory cells in the tissues of murine models of lung tissue damage and lower levels of TNF-1 and IL-6 production. Researchers have also speculated about Pal-GHK's potential to alleviate the oxidative stress of smoke inhalation. Research findings have led to the proposal that the amino-acid sequence of Pal-GHK might impede oxidative stress in alveolar epithelial cells by increasing Nrf2 (Nuclear factor erythroid 2-related factor 2) expression and reducing the levels of reactive oxygen species in cell cultures.(12) Nrf2 is a protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation. Pal-GHK peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Pickart, L., & Thaler, M. M. (1973). Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Nature: New biology, 243(124), 85–87. Gorouhi, F., & Maibach, H. I. (2009). Role of peptides in preventing or treating aged skin. International journal of cosmetic science, 31(5), 327-345. 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 Trookman, N. S., Rizer, R. L., Ford, R., Mehta, R., & Gotz, V. (2009). Clinical assessment of a combination lip treatment to restore moisturization and fullness. The Journal of clinical and aesthetic dermatology, 2(12), 44–48. Lintner, K., & Peschard, O. (2000). Biologically active peptides: from a laboratory bench curiosity to a functional skin care product. International journal of cosmetic science, 22(3), 207–218. https://doi.org/10.1046/j.1467-2494.2000.00010.x Schagen, S. K. (2017). Peptide treatments with effective anti-aging results. Cosmetics, 4(2), 16. Fournial, A., & Mondon, P. New Cosmetic or Dermopharmaceutical Use of a Mixture of a Ghk Tripeptide and Gqpr Tetrapeptide. 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. 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 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 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. 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 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.
PE-22-28 (8mg)
PE-22-28 is a synthetic derivative of the naturally occurring protein called spadin.(1) Spadin is a natural peptide derived from sortilin, an abundant protein in the central nervous system. PE-22-28 peptide is one such shortened peptide derivative of this protein; similar to spadin, PE-22-28 research indicates it primarily acts via the TREK-1 receptor. Researchers Djillani et al. commented that PE-22–28 may be "the shortest, most efficient sequence capable of blocking the TREK-1 channel" and may have a potentially higher potency in research settings than spadin.(2) TREK-1 (TWIK-related potassium channel) receptor is a two-pore potassium channel recently identified as a potential target for studying and modifying animal models of depression. In 2010, research(3) suggested that when TREK-1 receptors were removed from murine models, they became more resistant to depression. TREK-1 receptor is primarily found in the brain region, including the prefrontal cortex and hippocampus, i.e., areas governing mood, memory, and learning. Simulating the TREK-1 receptor may reduce neuron excitability, whereas reducing the receptor activity may increase neuron excitability.(4) While mainly evaluated in the study of depression models, this receptor may also play a strong role in anesthesia, pain perception, and protection of neurons. Overview Studies(1) have suggested that naturally occurring spadin blocks the TREK-1 channel, possibly exerting antidepressant activity for a specific duration. In order to improve the compound’s bioavailability and stability, scientists conducted several studies on spadin derivatives and analogs. One such study(1) was conducted on the seven amino acid spadin derivatives called PE-22-28. More specifically, the peptide corresponds to the chain from the 22nd to 28th amino acids of the original spadin sequence; hence, the reason behind the name PE-22-28. Similar to spadin, researchers theorized that these synthetic derivatives might bind to the TREK-1 channel, blocking activity and thereby producing mind stability and mood enhancement. Chemical Makeup Molecular Formula: C35H55N11O9 Molecular Weight: 773.89 g/mol Sequence: GVSWGLR Research and Clinical Studies PE-22-28 Peptide and Depression Researchers have suggested brain models of depression exhibit a smaller volume in the hippocampus. When presented with the PE-22-28 compound, the smaller volume may be increased and brought to an optimal threshold, potentially mitigating instances of synaptic feedback that lead to depressive episodes. Researchers propose that the peptide may have antidepressant potential through its proposed action in neurogenesis, which is supported by the cAMP signal cascade mechanism.(5) PE-22-28 Peptide and Post Stroke Depression (PSD) A study(4) was conducted where the experimental mice, induced with PSD, were presented with either the spadin peptide, or an SSRI compound (selective serotonin reuptake inhibitors). An SSRI, as the name suggests, is an antidepressant that is considered to prevent the reabsorption of serotonin neurotransmitters. While both compounds reportedly exhibited improvements in the mice, SSRIs may induce a wide range of additional unintended impacts, while PE-22-28 peptide is hypothesized not to. The SSRI compound also reportedly took longer to exhibit any action while the peptide was apparently fast-acting. PE-22-28 Peptide and Neurogenesis Studies have suggested that the peptide may exert neurogenesis (formation of neurons) and synaptogenesis (formation of synapses). Studies(6) were conducted where spadin derivatives were exposed in neuron cultures of mouse tissues. One study conducted in 2010 indicated subsequent MAPK and PI3K pathway activation, which might lead to neuron protection and formation. The other study suggested the peptide's potential to increase mRNA expression and concentration of brain-derived neurotrophic factor (BDNF) in the hippocampus.The hippocampus is considered critical in learning and memory processes. Hence, studies suggest that PE-22-28 may exhibit nootropic potential via possible action in the hippocampus region. Over time, organisms may exhibit a decline or downregulation of transcription factor cAMP response element-binding protein (CREB) activity in the brain, i.e., cAMP response element binding activity. CREB is considered critical for the growth and formation of neurons and may support memory recall and neuronal plasticity.(7) The findings of this 2010 study also suggested that spadin appeared to increase the number of bromodeoxyuridine (BrdU) positive cells in the hippocampus compared to saline-treated mice, hinting that PE-22-28, an analog of spadin, may potentially induce similar hippocampal neurogenesis. BrdU is considered a thymidine analog that integrates into the DNA of proliferating cells during the S-phase of the cell cycle, serving as a marker for cell division. Spadin apparently induced a rapid increase in BrdU-positive cells within 4 days, suggesting a quick activation of neurogenic pathways. This action persisted with long-term experimentation (15 days). As mentioned, a key component of spadin's rapid action might involve the activation of CREB, which may involve a specific link between CREB activation and hippocampal neurogenesis. The research analysis indicated that 4-day experimentation with spadin led to an apparent increase in phosphorylated CREB (pCREB), with levels four times higher than those seen in saline-treated controls. This phosphorylation suggests activation of CREB, confirmed by Western blot analysis showing the active form of CREB, while total CREB levels remained constant. Furthermore, the researchers observed a significant colocalization of pCREB with doublecortin (DCX), a marker of neuronal precursors, suggesting that CREB activation might be closely linked with the neurogenic process, specifically affecting neuronal rather than glial cells. These observations suggest that spadin, potentially through rapid CREB activation, may significantly enhance both the extent and speed of hippocampal neurogenesis, raising the possibility that PE-22-28 might similarly influence neurogenesis through these pathways.(3) PE-22-28 Peptide and Muscle Function TREK-1 receptor is also considered to impact muscles' ability to respond to outer stimulation. Upon stimulation, this receptor reportedly induces relaxation of the muscles, and consequently, blocks the receptors may lead to muscle contraction. Based on this understanding of the receptor, the PE-22-28 peptide is involved in ongoing research to establish its correlation with muscle relaxation and contraction.(8) PE-22-28 Peptide and Serotonin Signaling As mentioned, studies suggest that PE-22-28 may act as a blocker of the TREK-1 channel, akin to its natural analog spadin. This hypothesis is bolstered by research exploring these potential actions, particularly focusing on the connectivity between the medial prefrontal cortex (mPFC) and dorsal raphé serotonergic neurons in experimental models. The researchers observed that spadin might stimulate serotonin neurons and noted that the actions of spadin combined with serotonin agonists appeared additive, operating independently. Notably, adding a mGluR2/3 antagonist was suggested to inhibit the action of spadin, pointing towards a dependency of spadin on mPFC TREK-1 channels that are possibly linked to mGluR2/3 receptors. Consequently, it seems plausible that PE-22-28 may similarly interact with mGluR2/3 receptors, promoting the activation of serotonin neurons in a parallel fashion to spadin. Further investigations using immunohistochemical labeling revealed apparent interactions between spadin and the selective serotonin agonist RS 67333's actions on Zif268 expression in the dorsal raphé nucleus (DRN), indicating both additive and synergistic actions. Specifically, while individual concentrations of spadin or RS 67333 appeared to increase the number of Zif268-positive cells, their combination elevated these numbers dramatically, suggesting a strong depolarization of a subset of DRN neurons. Experiments involving the mGluR2/3 antagonist LY 341495 indicated that these may enhance the average firing rate of DRN serotonin neurons, a result that was abolished by an electrolytic lesion of the mPFC. This finding further implicates the mPFC TREK-1 channels linked to mGluR2/3 receptors regulating serotonin neuron activity. These observations are complemented by fluorescence microscopy studies using the ratiometric dye Fura2-AM to measure intracellular Ca2+ levels in cultured cortical neurons. The data posits that experiments combining spadin with LY 341495 or RS 67333 may increase intracellular Ca2+ levels compared to control or single exposures, with the most pronounced actions observed with the RS 67333 combination. This potentiation may be dependent on the stimulation of serotonin receptors, as blocking these receptors with GR 125487 appeared to eliminate the synergistic actions observed with RS 67333. Collectively, these findings underline a complex interplay between TREK-1 channel activity, mGluR2/3 receptor interaction, and serotonin neuron firing, mediated through the mPFC. The data suggest that spadin (and potentially PE-22-28 as a spadin-analog) may leverage these molecular mechanisms to influence serotonergic signaling, highlighting a nuanced interdependency between these pathways.(9) Indeed, scientists have theorized that by inhibiting TREK-1, PE-22–28 may increase serotonin transmission. They have commented that when “PE-22-28 is [presented to] the dorsal raphé nucleus, the peptide will block the channel and thereby activate the serotonergic neurons, resulting in the facilitation of serotonergic transmission”.(10) PE-22-28 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Front Pharmacol. 2017 Sep 12;8:643. https://pubmed.ncbi.nlm.nih.gov/28955242/ Djillani, A., Pietri, M., Mazella, J., Heurteaux, C., & Borsotto, M. (2019). Fighting against depression with TREK-1 blockers: Past and future. A focus on spadin. Pharmacology & therapeutics, 194, 185–198. https://doi.org/10.1016/j.pharmthera.2018.10.003 Mazella J, Pétrault O, Lucas G, Deval E, Béraud-Dufour S, Gandin C, El-Yacoubi M, Widmann C, Guyon A, Chevet E, Taouji S, Conductier G, Corinus A, Coppola T, Gobbi G, Nahon JL, Heurteaux C, Borsotto M. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biol. 2010 Apr 13;8(4):e1000355. https://pubmed.ncbi.nlm.nih.gov/20405001/ Djillani, A., Mazella, J., Heurteaux, C., & Borsotto, M. (2019). Role of TREK-1 in Health and Disease, Focus on the Central Nervous System. Frontiers in pharmacology, 10, 379. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470294/ Duman, R., Nakagawa, S. & Malberg, J. Regulation of Adult Neurogenesis by Antidepressant Treatment. Neuropsychopharmacol 25, 836–844 (2001). https://doi.org/10.1016/S0893-133X(01)00358-X Devader C, Khayachi A, Veyssière J, Moha Ou Maati H, Roulot M, Moreno S, Borsotto M, Martin S, Heurteaux C, Mazella J. In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin. Br J Pharmacol. https://pubmed.ncbi.nlm.nih.gov/25598009/ Mental health: spadin, a fast-acting antidepressant. https://journals.biologists.com/dmm/article/3/7-8/398/2435/Mental-health-spadin-a-fast-acting-antidepressant Lei Q, Pan XQ, Chang S, Malkowicz SB, Guzzo TJ, Malykhina AP. Response of the human detrusor to stretch is regulated by TREK-1, a two-pore-domain (K2P) mechano-gated potassium channel. J Physiol. 2014 Jul 15;592(14):3013-30. https://pubmed.ncbi.nlm.nih.gov/24801307 Moha ou Maati, Hamid et al. “The peptidic antidepressant spadin interacts with prefrontal 5-HT(4) and mGluR(2) receptors in the control of serotonergic function.” Brain structure & function vol. 221,1 (2016): 21-37. doi:10.1007/s00429-014-0890-x Okada, Masayoshi, and Ernesto Ortiz. "Viral vector-mediated expressions of venom peptides as novel gene therapy for anxiety and depression." Medical Hypotheses 166 (2022): 110910. 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.
Ipamorelin (5mg)
Ipamorelin is a synthetic peptide that is composed of five amino acids, otherwise known as a pentadecapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), formally classified as a Growth Hormone Secretagogue (GHS). Its name is derived from the intention of its development. Ipamorelin peptide was designed to act via ghrelin receptor binding. The ghrelin receptors on the pituitary gland (the gland naturally involved with growth hormone, or hGH synthesis) are also known as Growth Hormone Secretagogue receptors (GHS-R). Through its implied action, Ipamorelin may host the potential to trigger the GHS-Rs on the pituitary gland and potentially stimulate the release of growth hormone.(1) Overview Ipamorelin is the first synthetic GHS that appears highly selective and may have the potential to augment the production of hGH without affecting other pituitary hormones such as prolactin or adrenocorticotropic hormone (ACTH). The potential increase in hGH might promote lipolysis and insulin-like growth factor-1 (IGF-1) production synthesis. Consequently, IGF-1 may become a mediator of hGH’s anabolic actions, and thereby the peptide may act to increase cellular proliferation and bone and muscle anabolism.(1) Chemical Makeup Molecular Formula: C38H49N9O5 Molecular Weight: 711.86 g/mol Other Known Titles: NNC 26-0161 Research and Clinical Studies Ipamorelin Peptide and Selective Agonism Based on one 1998 murine model-based research study, researchers suggested that Ipamorelin may release growth hormones from the pituitary cells. When Ipamorelin was presented to swine and pentobarbitone anesthetized rats, it reportedly exhibited release in growth hormones. Upon further observation, the researchers hypothesized that similar to other growth hormone (GH) stimulating peptides, Ipamorelin may be a growth receptor agonist stimulating GH release through potential affinity in growth hormone receptors. Moreover, the researchers commented that Ipamorelin appears to be the first GHS-R “agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of Ipamorelin makes this compound a very interesting candidate for future clinical development.”(1) Scientific research studies have also suggested that Ipamorelin may lead to increased hGH secretion, possibly without significantly affecting other pituitary hormones such as the levels of prolactin or ACTH.(2) Ipamorelin Peptide and Growth Hormone Synthesis Studies conducted in vitro suggest that the interaction of Ipamorelin with GHS receptors may potentially affect somatotroph cells in the anterior pituitary gland by triggering a series of cellular signaling events.(3) This theorized pathway involves the activation of phospholipase C (PLC), which some researchers believe may lead to the increased release of inositol triphosphate (IP3) and diacylglycerol (DAG). This release of secondary messenger molecules such as IP3 might potentially stimulate the discharge of calcium ions (Ca2+) from the cell's internal stores, while DAG might activate protein kinase C (PKC). The subsequent rise in intracellular calcium levels and the possible activation of PKC are thought to result in the exocytosis of vesicles filled with growth hormones from these pituitary cells.(3) In late 1999, a clinical trial was carried out on eight test subjects where Ipamorelin was presented every 15 minutes for a set period. Two hours post-study, it was suggested by the researchers that the levels of growth hormone had apparently increased. More specifically, Ipamorelin appeared to have tended to boost growth hormone levels, potentially soaring to as much as 80mIU/l (roughly equivalent to a concentration of about 26.6ng/ml). When this increase is measured as a percentage compared to a placebo (with a baseline of 1.31mIU/l or 0.4ng/ml), the enhancement appeared to have exceeded a 60-fold uplift.(4) Ipamorelin Peptide and Bone Tissue It is conceivable that Ipamorelin may positively influence bone mineral density. The theory posits that Ipamorelin might stimulate osteoblasts (cells responsible for bone formation) via hGH-mediated mechanisms, potentially leading to their enhanced proliferation, growth, and specialization. In a particular study, murine models were exposed to either Ipamorelin or a placebo.(5) The impact of Ipamorelin on bone mineral density in these mice was monitored closely through real-time dual X-ray absorptiometry (DEXA) assessments at critical sites, including the femur and L6 vertebra. Post-experiment, the femur bones were further examined using mid-diaphyseal peripheral quantitative computed tomography (pQCT) scans. Preliminary findings implied that the peptide may have contributed to increased body mass and a probable elevation in the overall tibial and vertebral BMC (bone mineral content) as detected by DEXA compared to the placebo group. Further, the pQCT data appeared to suggest that the observed augmentation in cortical BMC may have stemmed from an enlargement in the cross-sectional area of the bone. In contrast, the cortical volumetric bone mineral density (BMD, which denotes the ratio of BMC to area) appeared to remain steady. Thus, there may have been an enlargement in the volumes of the femur and the L6 vertebrae since BMC appeared to increase while the volumetric BMDs appeared unchanged.(5) Ipamorelin Peptide and Digestion Researchers have delved into the potential of Ipamorelin in the functionality of the stomach, with a keen interest in its ability to possibly expedite the process of gastric emptying. For example, one study employed a technique to ascertain gastric emptying rates, which entailed monitoring the proportion of a marked substance that lingered in the stomach 15 minutes after its introduction through intragastric gavage.(6) The scientists conducted surgeries to purposefully decelerate the gastric emptying process in murine models. This deceleration was particularly noticeable in the control group. In contrast, Ipamorelin appeared to have markedly accelerated the emptying process compared to the control. This observation led the team to hypothesize that Ipamorelin might be able to increase the velocity of gastric emptying. Additional research was initiated to delve deeper into the action of the compound on the contractile potential of the stomach's smooth muscles, which were activated by acetylcholine and electrical field stimulation. Indeed, the decelerated peristalsis appeared to be mitigated when Ipamorelin and ghrelin were studied together, suggesting the idea that Ipamorelin may enhance the contractility of gastric smooth muscles.(6) Ipamorelin Peptide and Appetite The potential actions of Ipamorelin on ghrelin receptors may lead to an enhancement in hunger signals and, perhaps, an ensuing augmentation in body mass. Research suggests that research models exposed to Ipamorelin were observed to sustain an estimated 15% surge in body weight.(7) Researchers speculate that this substance might have led to a proportional increase in the weight of fat pads in comparison to the total body weight. Consequently, DEXA scans might indicate a comparative rise in body fat percentage. Moreover, there is speculation among researchers that Ipamorelin might elevate serum leptin levels, a hormone considered to play a crucial role in energy balance and hunger regulation. This observation has prompted scientists to consider increased food consumption as a potential contributor to the weight gain noted in research models exposed to Ipamorelin. They have posited that "GHSs increase body fat by GH-independent mechanisms that may include increased feeding.”(7) Ipamorelin Peptide and Nitrogen Balance Researchers have suggested that Ipamorelin may potentially mediate anabolic action, which may be due to its potential in hGH and IGF-1 synthesis and may be assessed through its impact on nitrogen balance. In a distinct investigation, researchers aimed to explore the action of Ipamorelin on specific liver markers associated with alpha-amino-nitrogen conversion during induced catabolic states.(8) The study focused on the liver’s capacity to synthesize urea-N (CUNS), which may serve as an indicator of the organ's ability to process nitrogen. The levels of messenger RNA (mRNA) related to liver urea cycle enzymes were scrutinized, alongside an assessment of the overall nitrogen balance and a hypothesis regarding nitrogen distribution across various organs. The findings suggested that Ipamorelin might have contributed to a possible 20% reduction in CUNS compared to the artificially induced catabolic condition. Furthermore, it might have diminished the expression of urea cycle enzymes, possibly restored nitrogen balance, and, in theory, altered or improved nitrogen concentrations in different organs.(8) Ipamorelin peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: K. Raun et al., Ipamorelin, the first selective growth hormone secretagogue, Endocrinology, November 1998. Sinha DK, Balasubramanian A, Tatem AJ, Rivera-Mirabal J, Yu J, Kovac J, Pastuszak AW, Lipshultz LI. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Transl Androl Urol. 2020 Mar;9(Suppl 2):S149-S159. doi: 10.21037/tau.2019.11.30. PMID: 32257855; PMCID: PMC7108996 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108996/ Jiménez-Reina, L., Cañete, R., de la Torre, M. J., & Bernal, G. (2002). Influence of chronic treatment with the growth hormone secretagogue Ipamorelin, in young female rats: somatotroph response in vitro. Histology and histopathology, 17(3), 707–714. https://doi.org/10.14670/HH-17.707 Gobburu, J.V.S., Agersø, H., Jusko, W.J. et al. Pharmacokinetic-Pharmacodynamic Modeling of Ipamorelin, a Growth Hormone Releasing Peptide, in Human Volunteers. Pharm Res 16, 1412–1416 (1999). 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 Greenwood-Van Meerveld, B., Tyler, K., Mohammadi, E., & Pietra, C. (2012). Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. Journal of experimental pharmacology, 4, 149–155. https://doi.org/10.2147/JEP.S35396 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 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.
Vialox (Pentapeptide-3V) (200mg)
Vialox, or pentapeptide-3, is a synthetic peptide molecule with the amino acid sequence GPRPA. It is believed to work by blocking neuronal nicotinic acetylcholine receptors located in the postsynaptic membrane of muscle cells. These receptors transmit signals from nerve cells to muscle cells, resulting in muscle contraction. By potentially reducing the release of acetylcholine, Vialox may relax muscles, reducing wrinkle depth and development along the skin barrier. The mechanism of action of Vialox may be similar to that of tubocurarine, a natural alkaloid compound considered to have muscle-relaxing activity. Chemical Makeup Molecular Formula: C21H37N9O5 Molecular Weight: 495.58 g/mol Other Known Titles: Pentapeptide-3V, SCHEMBL1552457, HY-P0099, ZINC35922739 Research and Clinical Studies Vialox Peptide Mechanism of Action Vialox is a synthetic peptide molecule suggested by researchers to be an inhibitor of neurotransmitter activity.(1) Vialox may act in a manner that is similar to that of tubocurarine, specifically through its interaction with acetylcholine receptors located on the postsynaptic membrane of muscle cells.(2) Tubocurarine is a naturally occurring alkaloid compound found in the bark of certain plants, particularly in the species Chondrodendron tomentosum, commonly known as "curare." It is considered to be a potent neurotoxin that appears to act as a non-depolarizing neuromuscular blocker by blocking the action of acetylcholine at the neuromuscular junction, thereby preventing muscle contraction. Researchers also classify Vialox as a non-depolarizing neuromuscular blocker. The peptide appears to bind to the acetylcholine receptors on the postsynaptic membrane of muscle cells. By doing so, studies report that it acts as "a competitive antagonist at the acetylcholine postsynaptic membrane receptor."(3) The peptide may possibly interact with the neuronal nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors reportedly play a crucial role in regulating muscle contraction by serving as the primary receptor in muscles for the communication between motor nerves and muscles at the neuromuscular junction. As an antagonist, Vialox appears to block the binding of acetylcholine to these receptor sites, thereby preventing the opening of the sodium ion channels responsible for depolarizing the cell and normally leading to muscle contraction.(4) By inhibiting the activity of the acetylcholine receptors, Vialox may cause the smooth muscles to stay relaxed, reducing wrinkles and fine lines in the skin. Vialox Peptide and Wrinkle Development, Skin Texture Vialox has been researched for its potential to reduce wrinkles upon the skin surface, and decrease texture variations along the skin barrier. There are some risks associated with using compounds to induce wrinkle reduction, particularly when used in higher concentrations or for extended periods. Furthermore, there is some concern that long-term exposure may have unknown or unanticipated impact. However, Vialox appears to have a short half-life and may be introduced less invasively. Nevertheless, it may be impactful, as researchers report that "studies [...] showed that this [compound] softened wrinkles and reduced skin roughness(4). These researchers reported that the tests appeared to result in reduced muscle contractions by 71% within one minute after Vialox presentation, leading to a 58% reduction two hours later. Ultimately, the scientists suggested that the reduced frequency of muscle contractions has the potential to result in shallower lines along the surface of the skin barrier. According to research, the peptide may also potentially mitigate the impact of skin wrinkles.(9) The results of the study indicate a noticeable decrease of 49% in the size of wrinkles, accompanied by a 47% decrease in the roughness of the skin within a time frame of 28 days of consistent presentation. Vialox peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Husein el Hadmed, H., & Castillo, R. F. (2016). Cosmeceuticals: peptides, proteins, and growth factors. Journal of cosmetic dermatology, 15(4), 514-519. Lupo, M. P., & Cole, A. L. (2007). Cosmeceutical peptides. Dermatologic therapy, 20(5), 343-349. Gorouhi, F., & Maibach, H. I. (2009). Role of peptides in preventing or treating aged skin. International journal of cosmetic science, 31(5), 327-345. Satriyasa B. K. (2019). Botulinum toxin (Botox) A for reducing the appearance of facial wrinkles: a literature review of clinical use and pharmacological aspect. Clinical, cosmetic and investigational dermatology, 12, 223–228. https://doi.org/10.2147/CCID.S202919 Kalandakanond, S., & Coffield, J. A. (2001). Cleavage of SNAP-25 by botulinum toxin type A requires receptor-mediated endocytosis, pH-dependent translocation, and zinc. The Journal of pharmacology and experimental therapeutics, 296(3), 980–986. Bakheit A. M. (2006). The possible adverse effects of intramuscular botulinum toxin injections and their management. Current drug safety, 1(3), 271–279. https://doi.org/10.2174/157488606777934431 Witmanowski, H., & Błochowiak, K. (2020). The whole truth about botulinum toxin - a review. Postepy dermatologii i alergologii, 37(6), 853–861. https://doi.org/10.5114/ada.2019.82795 Reddy, B. Y., Jow, T., & Hantash, B. M. (2012). Bioactive oligopeptides in dermatology: Part II. Experimental dermatology, 21(8), 569-575. 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.
MOTS-C (10mg)
MOTS-c (mitochondrial open-reading-frame of the 12S rRNA-c) peptide is a novel mitochondria-derived peptide. It is a short peptide composed of 16 amino acids, expressed in tissues and plasma, indicating a cell-specific and hormonal role.(1) With the potential to work both as a cell-specific compound and as a hormone, this peptide possibly acts by stimulating the AMP-activated protein kinase (AMPK) pathway. Only two mitochondrial-derived peptides (MDPs) have been studied, Humanin and MOTS-c. When metabolic stress occurs in the organism, the peptide is believed to translocate to the cellular nuclei and alter the gene expression. MOTS-c peptide may also be released extracellularly and is known as "mitochondrial hormone" or simply as "mitokine.”(2)(3) Chemical Makeup(4) Molecular Formula: C101H152N28O22S2 Molecular Weight: 2174.64 g/mol Other Titles: Mitochondrial-derived peptide MOTS-c, Mitochondrial open reading frame of the 12S rRNA-c Research and Clinical Studies Animal research models have indicated multiple potential actions from MOTS-c peptide, including increased physical performance, regulated cellular and tissue metabolism, and myoblast adaptation.(2) Research suggests that these actions may primarily depend on age and age-related changes in MOTS-c expression. The researchers suggest MOTS-c levels and activity might decline, hinting at a role in the cell aging process and the development of age-related metabolic dysfunction. Furthermore, MOTS-c may interact with known aging regulators, such as NAD+ and sirtuins, suggesting its involvement in pathways potentially modulating the lifespan of the cell.(1) As per Joseph C Reynolds et al., “Mitochondria are chief metabolic organelles with strong implications in cell aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome.”(4) The peptide endogenous expression has also been posited to be boosted via physical activity, potentially enhancing cellular metabolism.(5) MOTS-c Peptide and Muscle Metabolism With increasing age, skeletal muscles tend to gain insulin resistance, leading to decreased glucose uptake. Upon peptide exposure, skeletal muscles may be stimulated with an improved response toward AMPK activation. As a result, glucose transporter expression may increase, potentially improving skeletal muscle metabolism and enhancing skeletal muscle functioning and growth. Further, MOTS-c's actions are posited to include targeting metabolic pathways such as the folate-methionine cycle and purine biosynthesis. This targeting may potentially lead to a modulation of cellular metabolism, including actions on glucose uptake and lipid utilization. The peptide's impact might involve a shift in metabolic priorities within the cell, possibly affecting the balance between anabolic and catabolic processes. In systemic metabolism, MOTS-c is posited to function as a mitochondrial hormone, with circulating peptide levels appearing to affect metabolic functions in skeletal muscle and possibly adipose tissue. Its potential regulatory actions on glucose homeostasis and insulin action suggest a broader hormonal role in energy balance and nutrient sensing across different tissues.(1) MOTS-c Peptide and Fat Cell Metabolism Research has suggested that the peptide may potentially leave the mitochondrial site, translocate to cellular nuclei, and possibly alter gene expression. More specifically, the peptide may interact with a broad range of genes, particularly those with antioxidant response elements (ARE), hinting at a potential regulatory relationship with stress-responsive transcription factors like NRF2. Such findings suggest a genetically integrated system of mitonuclear communication, where both mitochondrial and nuclear genomes may encode factors that cross-regulate each other. This action, in turn, may alter glucose uptake restriction.(6) This hypothesis was first suggested from a study in which the experimental mice were given high-fat food, and only half were presented with the peptide. The researchers indicated that MOTS-c may potentially impact cellular metabolism by inhibiting the folate cycle directly tethered de novo purine biosynthesis, consequently leading to AMPK activation. Such actions hint at a broader role of the peptide in regulating insulin sensitivity and metabolic homeostasis, offering insights into its preventive potential against age-dependent and high-fat-induced insulin resistance and diet-induced obesity. The study presents supportive data to suggest that the peptide may stimulate glucose utilization, affect the methionine-folate cycle, and promote AMPK activation. These cellular actions suggest that MOTS-c might coordinate various metabolic processes, including glucose and lipid metabolism. Consequently, the murine models exposed to the peptide were lean and more energetic than the rest, further indicating that the peptide might prevent fat accumulation and induce glucose uptake via the AMPK pathway.(3) MOTS-c Peptide and Bone MOTS-c peptide has been suggested to regulate the transforming growth factor beta (TGF-beta)/SMAD pathway, which may profoundly affect bone tissues.(7) More specifically, MOTS-c's actions may involve the upregulation of TGF-β/Smad pathway-related genes, including TGF-β1, TGF-β2, and Smad7, suggesting a pivotal role of this pathway in MOTS-c mediated osteogenic differentiation. This hypothesis is further supported when the osteogenic differentiation promoted by MOTS-c is reversed upon TGF-β1 knockdown, indicating that MOTS-c's actions may be at least partly mediated through the TGF-β/Smad pathway. The peptide may also stimulate the expression of osteogenesis-related genes such as ALP, Bglap, and Runx2. Thus, this peptide may stimulate the SMAD pathway in the osteoblast cells, possibly improving bone density and strength. When studied in bone marrow cells, this compound appeared to trigger the differentiation of the stem cells, which may lead to bone tissue development. MOTS-c Peptide and Cardiac Function The peptide has not been suggested by researchers to directly influence cardiac function; instead, researchers posit that the peptide exerts potential on the endothelial cells that line the blood vessels inside. These endothelial tissues are considered to affect blood pressure and clotting. The researchers suspect a positive correlation exists between MOTS-c levels and microvascular and epicardial endothelial function. Such findings tentatively suggest MOTS-c as a potential biomarker for endothelial function, with the study revealing a nuanced relationship between MOTS-c levels and vascular reactivity. Further, the research suggested that when mice were exposed to MOTS-c, it appeared to improve the endothelial tissues' functioning, thereby possibly facilitating dysfunction. The mechanistic basis for MOTS-c's action on endothelial function remains speculative but may involve the activation of AMPK.(8) MOTS-c Peptide and Cell Lifespan Research has suggested that the peptide may be associated with enhanced longevity on a cellular level. The peptide typically contains glutamate residue, but when this is replaced by lysine, the new compound may exert a functional change. Scientists so far are aware that the functionality of the glutamate and lysine groups are vastly different, but how this specific structural change affects peptide functionality is yet to be understood. Noriyuki Fuku et al. suggests that there is “a biological link between MOTS-c and extended lifespan through the putative endocrine action of this mitokine. Further mechanistic research is needed to determine the functional significance of polymorphism and the potential influence of MOTS-c in the [...] aging process.” (9) The peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: Lee C, Kim KH, Cohen P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 2016 Nov;100:182-187. doi: 10.1016/j.freeradbiomed.2016.05.015. Epub 2016 May 20. PMID: 27216708; PMCID: PMC5116416. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116416/ Mohtashami Z, Singh MK, Salimiaghdam N, Ozgul M, Kenney MC. Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. Int J Mol Sci. 2022 Oct 9;23(19):11991. doi: 10.3390/ijms231911991. PMID: 36233287; PMCID: PMC9570330. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015 Mar 3;21(3):443-54. doi: 10.1016/j.cmet.2015.02.009. PMID: 25738459; PMCID: PMC4350682. Lu H, Wei M, Zhai Y, Li Q, Ye Z, Wang L, Luo W, Chen J, Lu Z. MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction. J Mol Med (Berl). 2019 Apr;97(4):473-485. doi: 10.1007/s00109-018-01738-w. Epub 2019 Feb 6. PMID: 30725119. https://pubmed.ncbi.nlm.nih.gov/30725119/ Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021 Jan 20;12(1):470. https://pubmed.ncbi.nlm.nih.gov/33473109/ Kim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab. 2018 Sep 4;28(3):516-524.e7. doi: 10.1016/j.cmet.2018.06.008. Epub 2018 Jul 5. PMID: 29983246; PMCID: PMC6185997. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185997/ Hu BT, Chen WZ. MOTS-c improves osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via TGF-β/Smad pathway. Eur Rev Med Pharmacol Sci. 2018 Nov;22(21):7156-7163. doi: 10.26355/eurrev_201811_16247. PMID: 30468456. https://pubmed.ncbi.nlm.nih.gov/30468456/ Qin Q, Delrio S, Wan J, Jay Widmer R, Cohen P, Lerman LO, Lerman A. Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction. Int J Cardiol. 2018 Mar 1;254:23-27. doi: 10.1016/j.ijcard.2017.12.001. Epub 2017 Dec 6. PMID: 29242099. https://pubmed.ncbi.nlm.nih.gov/29242099/ Noriyuki Fuku el al., The mitochondrial-derived peptide: A player in exceptional longevity?, http://dx.doi.org/10.1111/acel.12389. 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.
Semax (25mg)
Semax peptide is a synthetic polypeptide analog of an adrenocorticotropic hormone fragment 4-7 (ACTH 4-7),(1) a hormone secreted by the anterior pituitary gland. This fragment has been reported by researchers not to exhibit any action characteristic of ACTH itself but may have a potentially specific action within the brain.(2) Researchers find that naturally occurring peptides may occasionally exhibit instability and easy degradation by biological enzymes, such as those found in gastrointestinal and cerebrospinal fluids. Consequently, researchers aim to synthesize analogs of these naturally occurring but potentially unstable peptides to induce similar biological action with the added value of higher stability. Semax is one such synthetically developed derivative of an endogenous adrenocorticotropic hormone fragment. The Met-Glu-His-Phe sequence in Semax is extended by adding a Pro-Gly-Pro (PGP) sequence at its C-terminal end. This modification with PGP may potentially enhance the molecule's ability to cross the blood-brain barrier (BBB) by increasing its lipophilicity. This increase in lipophilicity may facilitate the molecule’s passive diffusion or uptake through mechanisms such as lipid raft-mediated endocytosis, which may circumvent the tight junctions that typically restrict entry into the brain. Furthermore, the presence of PGP at the peptide's C-terminus might also modify its interactions with specific transporters or receptors on the BBB, potentially favoring its transport via receptor-mediated transcytosis. Moreover, the acetylation of Semax may improve its stability by making it more resistant to enzymatic breakdown, thereby extending its half-life in biological settings. Overview Synthetically developed Semax has been widely researched for its potential mechanism of action and lauded for its apparent biological stability. Researchers suggest it may inhibit select enzymes that regulate the degradation of enkephalins, naturally released neurotransmitters secreted in the brain, which scientists consider may regulate several biological functions. Enkephalins are believed to be significantly involved in nociception (the sensory perception of pain) and stress response. Moreover, an elevation in enkephalin concentrations might potentially impact other neurotransmitter systems due to the intricate interconnections between the opioid system and neurotransmitters such as dopamine and serotonin. This interaction may manifest through modulation or alteration of neurotransmitter release, receptor activity, or signal transduction pathways, indicating a sophisticated and multifaceted relationship that remains an area of active research. In addition to enkephalins, Semax has been evaluated for its potential to inhibit other peptide-degrading secreted enzymes. Based on one specific research study,(4) Semax may induce elevated secretion and release of dopamine as well as possibly increasing the levels of brain-derived neurotrophic factor (BDNF). Based on another study,(5) Semax has been speculated to also host the potential to alter gene expressions that modulate the immune system. In altering gene expression, the levels of immune cells and their mobility may be elevated. Semax was reported by researchers to exhibit altering potential in the encoding of chemokines and immunoglobulins, related to the functioning of the vascular system. Chemical Makeup Molecular Formula: C39H54N10O10S Molecular Weight: 854.99 g/mol Other Known Titles: ACTH (4-7)PGP, HY-P1146 Research Studies and Clinical Trials Semax Peptide and Nootropic Action An initial study(6) was conducted on ACTH hormone and its analogs, including Semax, to determine its nootropic potential in murine models. After peptide exposure in the models, 5-hydroxyindoleacetic acid (5-HIAA) levels were monitored. 5-HIAA levels appeared elevated by 25% after 2 hours of Semax presence. The levels appeared to increase gradually up to a maximum of 180% within 4 hours of peptide exposure. It was noted by researchers that the peptide, when introduced 20 minutes before D-amphetamine, appeared to lead to an elevation of 5-HIAA as compared to exposure to Semax alone. 5-HIAA is a primary metabolite of serotonin, which indicates that Semax might enhance serotonergic activity. This hypothetical influence on serotonin metabolism might enhance the functions of serotonin-dependent pathways, which may affect operations within the central nervous system. This speculative action underscores a possible modulation of neurotransmitter systems that play critical roles in mood, cognition, and overall brain function. Semax Peptide and Neonatal Anxiety Models The main aim of this study(7) was to expose neonatal murine models to an SSRI and then Semax, to evaluate the interaction. Murine models aged between 1 and 14 days received an SSRI, followed by Semax on days 15 to 28. After 28 days, it was noted that upon exposure to the SSRI, the rats exhibited anxiety-like behavior, with an apparently impaired response to stressors and new stimuli during the first 14 days. Following Semax exposure, these SSRI-induced actions appeared to be mitigated, with the rats even exhibiting improved learning abilities and an overall reduction in anxiety-driven behaviors. Researchers posited that Semax might have reestablished normal levels of monoamines in the brain, which may have been initially decreased by the SSRI. By affecting these neurotransmitter systems, Semax might restore or stabilize neural pathways that were previously disrupted. Such changes might balance the excitatory and inhibitory signals in the brain, creating a state more conducive to reduced anxiety. For instance, by potentially increasing serotonin levels, Semax may improve mood and decrease anxiety, while optimizing dopamine might enhance motivation and reward processing. Furthermore, norepinephrine adjustments might improve attention and vigilance. Behavioral assessments conducted in the experiment indicated that these potential actions of Semax appeared temporally stable. The reduction in anxiety-related behaviors was sustained from adolescence through young adulthood, suggesting that Semax might have a lasting influence on neural circuits. This enduring stability implies that Semax might support creating a protective or corrective action on these circuits that persists beyond immediate exposure. Semax Peptide and the Vascular System In this study,(8) researchers evaluated the potential of Semax to protect murine heart models from vascular damage after experimental myocardial infarction (MI). The murine models were induced with myocardial infarction, and a cohort of the models were exposed to Semax in an experimental group for the following 6 days. On the 28th day, it was reported by the researchers that the murine models that served as a control group appeared to have developed cardiac hypertrophy along with decreased arterial blood pressure. The Semax-exposed models exhibited signs indicating preventing diastolic pressure growth in the left ventricle, with apparent left ventricle remodeling. Notably, the peptide may have ameliorated both cardiomyocyte hypertrophy and the imbalance between the growth of contractile and mitochondrial apparatus. Semax Peptide and Neonatal Deprivation Adolescent rats(9) were separated from their mothers for approximately 5 hours per day during postnatal days 1 to 14. From days 15 to 28, these adolescent rats were then exposed to the Semax peptide. After 28 days, it was found that during maternal deprivation, when Semax was not present, there was an apparent increase in anxiety and physical and emotional reactivity in the rats. Upon Semax exposure, researchers reported that reactions and anxiety in the rats appeared restored to control levels. Semax Peptide and Neuroprotection This clinical trial(10) was conducted on 100 models of ischemic stroke. A cohort representing 30% of the models was exposed to Semax, whereas the rest were evaluated as a control group. Following the study, researchers reported that following Semax exposure, there appeared to be an improvement in the rate of restoration of damaged neurological functions. All results were analyzed using EEG mapping. Semax Peptide and Nootropic Properties A small-scale clinical trial(11) was conducted in which research models were given Semax under high-stress conditions, and subsequent brain activity was monitored. At the end of the study, after a total of 24 hours, researchers reported that compared to normal pre-trial thresholds, the models appeared to exhibit increased memory recall and increased focus intervals. Semax peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: T. Kolomin et al., A New Generation of Drugs: Synthetic Peptides based on Natural Regulatory peptides. Neuroscience & Medicine, 2013, 223-252. Published Online December 2013. http://dx.doi.org/10.4236/nm.2013.44035 Dornbush RL, Nikolovski O. ACTH 4-10 and short-term memory. Pharmacol Biochem Behav. 1976;5(Suppl 1):69-72. doi: 10.1016/0091-3057(76)90331-2. PMID: 189333. https://pubmed.ncbi.nlm.nih.gov/189333/ Kost NV, Sokolov OIu, Gabaeva MV, Grivennikov IA, Andreeva LA, Miasoedov NF, Zozulia AA. Ingibiruiushchee deĭstvie semaksa i selanka na énkefalindegradiruiushchie fermenty syvorotki krovi cheloveka [Semax and selank inhibit the enkephalin-degrading enzymes from human serum]]. Bioorg Khim. 2001 May-Jun;27(3):180-3. Russian. doi: 10.1023/a:1011373002885. PMID: 11443939. https://pubmed.ncbi.nlm.nih.gov/11443939/ Shih-Jen Tsai, Semax, an analogue of adrenocorticotropin (4–10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome, Medical Hypotheses, Volume 68, Issue 5, 2007, Pages 1144-1146. https://doi.org/10.1016/j.mehy.2006.07.017 Medvedeva, E.V., Dmitrieva, V.G., Povarova, O.V. et al. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC Genomics 15, 228 (2014). https://doi.org/10.1186/1471-2164-15-228 Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005 Dec;30(12):1493-500. doi: 10.1007/s11064-005-8826-8. PMID: 16362768. Nataliya Yu. Glazova, Daria M. Manchenko, Maria A. Volodina, Svetlana A. Merchieva, Ludmila A. Andreeva, Vladimir S. Kudrin, Nikolai F. Myasoedov, Natalia G. Levitskaya, Semax, synthetic ACTH(4–10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats, Neuropeptides, Volume 86, 2021, 102114, ISSN 0143-4179. https://doi.org/10.1016/j.npep.2020.102114 Gavrilova SA, Golubeva AV, Lipina TV, Fominykh ES, Shornikova MV, Postnikov AB, Andrejeva LA, Chentsov IuS, Koshelev VB. [Protective effect of peptide semax (ACTH(4-7)Pro-Gly-Pro) on the rat heart rate after myocardial infarction]. Ross Fiziol Zh Im I M Sechenova. 2006 Nov;92(11):1305-21. Russian. PMID: 17385423. https://pubmed.ncbi.nlm.nih.gov/17385423/ Volodina MA, Sebentsova EA, Glazova NY, Levitskaya NG, Andreeva LA, Manchenko DM, Kamensky AA, Myasoedov NF. Semax attenuates the influence of neonatal maternal deprivation on the behavior of adolescent white rats. Bull Exp Biol Med. 2012 Mar;152(5):560-3. English, Russian. doi: 10.1007/s10517-012-1574-2. PMID: 22803132. https://pubmed.ncbi.nlm.nih.gov/22803132/ Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat'ko VN, Zhuravleva EIu, Vanichkin AV. Effektivnost' semaksa v ostrom periode polusharnogo ishemicheskogo insul'ta (klinicheskoe i élektrofiziologicheskoe issledovanie) [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. Russian. PMID: 11517472. https://pubmed.ncbi.nlm.nih.gov/11517472/ Asmarin IP, Nezavibat'ko VN, Miasoedov NF, Kamenskiĭ AA, Grivennikov IA, Ponomareva-Stepnaia MA, Andreeva LA, Kaplan AIa, Koshelev VB, Riasina TV. Nootropnyĭ analog adrenokortikotropina 4-10-semaks (15-letniĭ opyt razrabotki i izucheniia) [A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its design and study)]. Zh Vyssh Nerv Deiat Im I P Pavlova. 1997 Mar-Apr;47(2):420-30. Russian. PMID: 9173745. https://pubmed.ncbi.nlm.nih.gov/9173745/ 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.
DSIP (5mg)
Delta Sleep-Inducing Peptide, or DSIP, is a naturally-occurring peptide made of nine amino acids, isolated from the central nervous system of experimental models of electrically induced sleep. DSIP is posited to regulate the sleep cycle, as suggested by its name, but may also play a role in regulating various physiological processes. Suggested to induce delta sleep in test models, this neuropeptide also appears to impact electrophysiological activity and possibly regulate the neurotransmitter levels in the brain.(1) DSIP peptide was first characterized and examined from 1963 to 1977 and has since been widely studied by scientists.(2) Initially regarded only for its potential as a sleep-including factor, DSIP was soon suggested to induce other potential actions, such as mitigating pain, sleep cycle regulation, and mitigating withdrawal.(3) Mechanisms of Action DSIP is believed to have the potential to modify the structure and quality of sleep by engaging with the central nervous system. It is thought that DSIP may potentially reduce the time it takes to fall asleep and enhance the overall quality of sleep by influencing the activity of various neurotransmitters within the brain. Despite these possibilities, scientific research has yet to definitively identify the primary mechanisms and pathways through which DSIP exerts its actions. However, it is hypothesized that DSIP may target several specific receptors, which are considered crucial in its function. These include: N-methyl-D-aspartate (NMDA) receptors and gamma-aminobutyric acid (GABA) receptors: NMDA receptors are linked to glutamate, a vital neurotransmitter that facilitates brain excitation, while GABA receptors are associated with inhibitory neurotransmission, playing a significant role in calming the brain. Research conducted on murine models has suggested that DSIP might amplify GABA's calming actions, which assists in reducing brain activity and helps individuals fall asleep more easily. Concurrently, murine studies suggest that DSIP may dampen some of the stimulatory impacts of NMDA receptors, thereby decreasing overall brain stimulation and further aiding in sleep promotion.(4)(5) Opioid receptors: Further research indicates that DSIP might indirectly affect opioid receptors in the brain. This interaction is believed to influence the peptide's ability to modulate sleep and alleviate withdrawal symptoms, highlighting its complex involvement in the brain's signaling systems.(6)(7) Alpha 1-adrenergic receptor: This receptor, apparently found in the pineal gland, has been another focus of DSIP research. An experimental study has suggested that DSIP's modulation of the alpha 1-adrenergic receptor could be a mechanism through which it affects sleep patterns. This interaction also hints at DSIP's potential role in managing stress tolerance, given the significant influence of alpha 1-adrenergic signaling in stress-related processes.(8) These findings underline the complex and multifaceted ways in which DSIP might influence sleep and stress management, although more research is needed to understand its mechanisms of action. Chemical Makeup Molecular Formula: C35H48N10O15 Molecular Weight: 848.82 g/mol Other Known Titles: DSIP nonapeptide; emideltide Research and Clinical Studies DSIP and Sleep Cycles A study(9) was conducted on feline models to examine the potential action of DSIP on sleep patterns. The models were divided into two groups; one was a control, and the other was labeled as the DSIP group. The peptide was presented to the cats and was monitored for 8 hours. Results indicated that there appeared to be a significant increase in total sleep and slow wave sleep (SWS) in the DSIP group. The action of DSIP appeared to be immediate as the amount of SWS sleep elevated within the first hour following study initiation. This increase appeared to be maintained for 7 hours and then decreased in the eighth hour. SWS, often called deep sleep, is suggested as one of the core stages within sleep architecture, broadly categorized into non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. The overall structure of sleep is typically cyclic, alternating between NREM and REM stages multiple times. Apparently, SWS falls under the NREM category and scientists detect it by its low-frequency, high-amplitude delta waves evident in electroencephalogram (EEG) recordings. Sleep begins with NREM sleep, subdivided into three stages: N1, N2, and N3. N1 and N2 are lighter stages of sleep, while N3, synonymous with SWS, is the deepest stage of sleep. Following the deep sleep stage, the cycle progresses into REM sleep, where brain activity increases and dreams occur. A clinical study(10) has suggested that the peptide may lead to an immediate increase in sleep pressure and resulted in a 59% increase in sleep within two hours of initiating DSIP experimentation. The scientists also posited that the peptide may have enhanced sleep efficiency, potentially by shortening sleep onset.(10) DSIP and Endocrine Regulation DSIP has been posited to interact with certain hormonal messengers typically released during sleep. Examples may include the luteinizing hormone (LH), which is considered a crucial hormone in the regulation of reproductive hormones such as testosterone. In a study with murine models,(11) DSIP was examined for its potential actions on the endocrine system. Within 30 minutes, it was noted that the levels of LH appeared to be significantly elevated, whereas there was no perceived impact on another regulatory messenger called follicle-stimulating hormone (FSH). Further studies have suggested that DSIP may lead to increased secretion of growth hormone, positing that the peptide may potentially act on the hypothalamus to regulate hormonal secretion. Utilizing ovariectomized murine models to exclude the actions of gonadal steroids, the research observed an apparent elevation in GH levels caused by DSIP. The potential involvement of a dopaminergic mechanism in this process was inferred from the blocking action of pimozide, a dopamine antagonist, on the DSIP-induced GH increase. Additionally, in vitro studies with pituitary cells suggest a similar increase in GH release upon exposure to DSIP, albeit with a notable decline at higher concentrations. This pattern hints at the complex nature of DSIP's role in GH regulation, potentially linking it to sleep-induced GH release, given the peptide's association with slow-wave sleep patterns and the apparent correlation of such sleep phases with GH secretion.(12) DSIP and Stress Response Researchers have investigated the potential action of DSIP on murine models subjected to experimentally induced stress.(13) The murine models were divided into six groups, where the control group was presented with a placebo and the rest with DSIP. The six groups included (i) control group, (ii) stress group, (iii) group with DSIP one hour before stress experiments, (iv) DSIP 24 hours before stress experiments, (v) DSIP one hour before the last stress experiment and (vi) DSIP 24 hours before the last stress experiment. This research primarily focused on assessing changes in substance P, beta-endorphin, and corticosterone levels, which are critical in understanding the stress response and potential modulatory impacts of DSIP. Initial findings highlighted that DSIP exposure might induce noticeable fluctuations in the levels of these markers, suggesting a possible stress-modulatory role. For instance, there was an initial decrease followed by a dramatic increase in beta-endorphin. This pattern suggests DSIP's potential influence on the opioidergic system, possibly contributing to mechanisms of stress mitigation or adaptation. Regarding corticosterone levels, which directly indicate stress in murine models, a decrease was noted shortly after DSIP exposure. The study posits that DSIP's actions on substance P, beta-endorphin, and corticosterone levels are part of a broader spectrum of biochemical changes, hinting that DSIP might initiate a series of molecular reactions contributing to its stress-modulatory actions.(13) DSIP and Longevity A study(14) was conducted on murine models, equally divided into DSIP and control groups. The researchers suggested that DSIP did not appear to influence food intake, however, it did apparently decrease the weight of the murine models. It appeared to decrease the chromosomal aberrations in the bone marrow by 23% and improve the life span by 24% compared to the control group. Moreover, DSIP also appeared to lead to a 2.5-fold decrease in the occurrence of malignancies. Another study suggests that the apparent protective actions of DSIP may be due to the potential antioxidative properties of the peptide. The study(15) was conducted on murine models, and the researchers posited that DSIP may inhibit the levels of malonic dialdehyde in the models. Malonic dialdehyde is a byproduct of lipid peroxidation, and increased levels of malonic dialdehyde typically induce increased oxidative stress. This suggested that DSIP may prevent lipid peroxidation in the murine models, which may execute antioxidant properties. DSIP may also stimulate the endogenous antioxidant system, influencing various enzymatic levels. The researchers commented that “DSIP exerts stimulating influence upon the superoxid-dismutese, catalase, ceruloplasmin activities as well as the level of nonenzymatic antioxidants--urea and uric acids, because during organism aging the antioxidant defense systems are being suppressed. DSIP increases the volume of tissues and blood endogenous antioxidant defense system mainly by means of enzymatic antioxidant system, especially during later ontogenesis.”(15) DSIP is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: National Center for Biotechnology Information. "PubChem Compound Summary for CID 3623358, Emideltide;delta Sleep Inducing Peptide" PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/3623358 Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): an update. Peptides. 1986 Nov-Dec;7(6):1165-87. https://pubmed.ncbi.nlm.nih.gov/3550726/ Kovalzon VM, Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle. J Neurochem. 2006 Apr;97(2):303-9. https://pubmed.ncbi.nlm.nih.gov/16539679/ Grigor'ev VV, Ivanova TA, Kustova EA, Petrova LN, Serkova TP, Bachurin SO. Effects of delta sleep-inducing peptide on pre- and postsynaptic glutamate and postsynaptic GABA receptors in neurons of the cortex, hippocampus, and cerebellum in rats. Bull Exp Biol Med. 2006 Aug;142(2):186-8. English, Russian. doi: 10.1007/s10517-006-0323-9. PMID: 17369935 Sudakov KV, Umriukhin PE, Rayevsky KS. Delta-sleep inducing peptide and neuronal activity after glutamate microiontophoresis: the role of NMDA-receptors. Pathophysiology. 2004 Oct;11(2):81-86. https://pubmed.ncbi.nlm.nih.gov/15364118/ Nakamura A, Nakashima M, Sakai K, Niwa M, Nozaki M, Shiomi H. Delta-sleep-inducing peptide (DSIP) stimulates the release of immunoreactive Met-enkephalin from rat lower brainstem slices in vitro. Brain Res. 1989 Feb 27;481(1):165-8. doi: 10.1016/0006-8993(89)90498-8. PMID: 2706459. Dick P, Grandjean ME, Tissot R. Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors. Neuropsychobiology. 1983;10(4):205-8. doi: 10.1159/000118012. PMID: 6328354. Graf MV, Schoenenberger GA. Delta sleep-inducing peptide modulates the stimulation of rat pineal N-acetyltransferase activity by involving the alpha 1-adrenergic receptor. J Neurochem. 1987 Apr;48(4):1252-7. doi: 10.1111/j.1471-4159.1987.tb05654.x. PMID: 3029331. Susić V, Masirević G, Totić S. The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat. Brain Res. 1987 Jun 30;414(2):262-70. https://pubmed.ncbi.nlm.nih.gov/3620931/ Schneider-Helmert D, Gnirss F, Monnier M, Schenker J, Schoenenberger GA. Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior. Int J Clin Pharmacol Ther Toxicol. 1981 Aug;19(8):341-5. https://pubmed.ncbi.nlm.nih.gov/6895513/ Iyer KS, McCann SM. Delta sleep inducing peptide (DSIP) stimulates the release of LH but not FSH via a hypothalamic site of action in the rat. Brain Res Bull. 1987 Nov;19(5):535-8. doi: 10.1016/0361-9230(87)90069-4. https://pubmed.ncbi.nlm.nih.gov/3121137/ Iyer KS, McCann SM. Delta sleep-inducing peptide (DSIP) stimulates growth hormone (GH) release in the rat by hypothalamic and pituitary actions. Peptides. 1987 Jan-Feb;8(1):45-8. doi: 10.1016/0196-9781(87)90163-x. PMID: 3575154. Sudakov KV, Coghlan JP, Kotov AV, Salieva RM, Polyntsev YuV, Koplik EV. Delta-sleep-inducing peptide sequels in the mechanisms of resistance to emotional stress. Ann N Y Acad Sci. 1995 Dec 29;771:240-51. https://pubmed.ncbi.nlm.nih.gov/8597403/ Popovich IG, Voitenkov BO, Anisimov VN, Ivanov VT, Mikhaleva II, Zabezhinski MA, Alimova IN, Baturin DA, Zavarzina NY, Rosenfeld SV, Semenchenko AV, Yashin AI. Effect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice. Mech Ageing Dev. 2003 Jun;124(6). https://pubmed.ncbi.nlm.nih.gov/12782416/ Bondarenko TI, Maĭboroda EA, Mikhaleva II, Prudchenko IA. [Mechanism of delta-sleep inducing peptide geroprotective activity]. Adv Gerontol. 2011;24(1):80-92. Russian. https://pubmed.ncbi.nlm.nih.gov/21809625/ 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 NO DAC (Mod GRF 1-29) (5mg)
CJC-1295 is a synthetic peptide derivative of the naturally occurring GHRH hormone and is composed of 29 amino acids.(2) This peptide is also referred to as Modified GRF (1-29) or CJC 1295 without DAC. It is a modified version of the peptide containing four substituted amino groups that are considered to help prevent the peptide's degradation. CJC without DAC does not have a Drug Affinity Complex that is sometimes added to further extend the half-life of the peptide. Modified growth hormone fragments GRF (1-29) were first discovered in the early 1980s, when it was suggested that the first 29 amino acids of the natural growth hormone-releasing hormone might retain all the properties of the full 44 amino acid peptide.(3) One of the potential drawbacks of synthetically developed growth hormone-releasing peptides is a short half-life. Rigorous research has resulted in a supposedly stabilized, longer-lasting CJC-1295 (No DAC) peptide.(1) Overview CJC-1295 without DAC, alternatively known as the tetra-substituted GRF (1-29), represents a synthetic variant of the naturally occurring hormone responsible for the release of growth hormone (GHRH). Scholars have posited that it facilitates the secretion of growth hormone (GH). This compound is essentially constructed from the minimal sequence of amino acids that might bind to GHRH receptors, specifically the initial 29 amino acids of GHRH. There are notable structural differences between CJC-1295 without DAC and the unmodified fragment, primarily due to the alteration of four amino acids within the original 29 amino acids of GHRH. These changes encompass the 2nd, 8th, 15th, and 27th amino acids, and such adjustments might arguably extend the peptide's lifespan against enzymatic breakdown, particularly by enzymes like dipeptidyl peptidase-4 (DPP-4).(4) More specifically, these alterations include: The replacement of L-alanine with D-alanine at the 2nd position, which is thought to bolster resistance against molecular degradation. The substitution of asparagine with glutamine at the 8th position, which could conceivably minimize asparagine reconfiguration and amide hydrolysis. The exchange of glycine for alanine at the 15th position, which is speculated to enhance bioactivity. The alteration from methionine to leucine at the 27th position, which is suggested to prevent methionine oxidation. Chemical Makeup Molecular Formula: C152H252N44O42 Molecular Weight: 3367.9 g/mol Other Known Titles: CJC-1295 Without DAC Research and Clinical Studies CJC-1295 (No DAC) Peptide and the Pituitary Gland CJC-1295 without DAC seems to aim at the GHRH receptor on pituitary cells, potentially engaging with certain binding sites on the receptor molecule. This interaction may induce alterations in the receptor's conformation, possibly sparking a chain of molecular events that might activate signaling pathways within its target cells. The induced structural changes are believed to facilitate the activation of G-proteins, signaling proteins theorized to reside on the cell's interior side of the GHRH receptor.(5) Once activated, these G-proteins might trigger the production of secondary messengers like cAMP or IP3, which are thought to act as intermediary signaling molecules, possibly amplifying the signal inside the cell. Particularly, cAMP may activate protein kinases, which are presumed to be pivotal in phosphorylating specific target proteins.(6) Protein kinases are suggested to have a potential role in managing various cell functions. The stimulation of protein kinases could lead to the phosphorylation of transcription factors, proteins that might influence gene expression regulation. These phosphorylated transcription factors may then enter the nucleus and might alter the transcription of genes linked to the synthesis and secretion of growth hormone. Consequently, the molecular activities seemingly initiated by CJC-1295 no DAC's binding may culminate in the merging of secretory vesicles loaded with growth hormone with the cell membrane. This merger may facilitate the external release of growth hormone from the pituitary cells, potentially enabling it to perform its biological functions. CJC-1295 (No DAC) Peptide and Growth Hormone Pulsatility While no studies directly investigate the potential of CJC-1295 no DAC (tetrasubstituted GRF 1-29), some researchers have conducted extensive experimentations with partially modified versions of GRF 1-29. One notable example is research by Khorram et al. This study on CJC-1295 no DAC explored its potential on growth hormone and insulin-like growth factor 1 (IGF-1), skin cell proliferation, muscle tissue hypertrophy, and other potential outcomes.(7) The investigation highlighted the potential of CJC-1295 no DAC to modulate the growth hormone-IGF-1 axis. More specifically, CJC-1295 no DAC appeared to cause a considerable rise, with an approximate increase of 70-107% higher mean 12-hours release of growth hormone by the somatotroph cells in the anterior pituitary. Concurrently, IGF-1 also experienced an increase, approximately 28%, indicating an enhancement in the growth hormone-IGF-1 axis functionality. This increase was also associated with increases in skin tissue thickness, potentially due to the anabolic actions of growth hormone and IGF-1 on collagen-producing skin cells such as fibroblasts. Furthermore, there was a significant increase in muscle tissue hypertrophy, ultimately resulting in a net lean mass gain of 2.77 lbs. These results imply a potential role of CJC-1295 no DAC in promoting skin cell proliferation and muscle tissue hypertrophy that should be investigated in future experiments. However, the specific mechanisms behind these actions remain to be fully elucidated. CJC-1295 (No DAC) Peptide and Intestinal Studies Studies(8) were conducted in experimental models, which have suggested a potential interaction between GHRH analog peptides and VPAC(1)-R, found on the smooth muscles of the gastrointestinal system. This interaction was suggested to induce bowel movement, though the potential connection between specific peptides and bowel release are still under investigation. CJC-1295 (No DAC) Peptide and Heart Rate Preliminary research(9) in murine models suggested that Modified GRF 1-29 peptide (along with other GHRH derivative analogs) may exhibit some potential to improve heart rate and possibly support the heart's ability to pump blood, particularly following a heart attack. The study(9) commented that GHRH agonist peptides appeared to promote cardiac tissue repair and possibly also improve ejection fraction rates. CJC-1295 (No DAC) Peptide and Combination CJC-1295 NO DAC appears to be a relatively short-lasting GHRH analog when not attached to DAC, compared to other synthetic GHRH peptides. Consequently, combined with other short-acting peptides, it may support longer durations for specific properties. Moreover, the peptide may have synergistic actions when combined with growth hormone secretagogues (GHSs). GHSs are considered to be ghrelin mimetics, which interact with the ghrelin receptors within various tissues. These receptors also happen to be found on the somatotroph cells in the anterior pituitary gland - the same cells that also have the GHRH receptors and are associated with growth hormone synthesis. Activating these receptors may lead to an apparent increase in growth hormone synthesis, and some researchers suggest that the simultaneous activation of the GHRH and ghrelin receptors on these pituitary cells may result in synergistically increased growth hormone elevation.(11) One such highly common peptide combination is with Ipamorelin, a synthetic GHRH pentapeptide. Both Ipamorelin and CJC-1295 peptides have been suggested to stimulate the production of growth hormone by the cells of the pituitary gland, albeit via different modes of action, therefore possibly exerting synergism and stimulating even greater growth hormone secretion. CJC-1295 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: National Center for Biotechnology Information. "PubChem Compound Summary for CID 91976842, CJC1295 Without DAC" PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/CJC1295-Without-DAC Clark, R G, and I C Robinson. “Growth induced by pulsatile infusion of an amidated fragment of human growth hormone releasing factor in normal and GHRF-deficient rats.” Nature vol. 314,6008 (1985): 281-3. https://pubmed.ncbi.nlm.nih.gov/2858818/ The Discovery of Growth Hormone-Releasing Hormone: An Update https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2826.2008.01740.x Martin, B., Lopez de Maturana, R., Brenneman, R., Walent, T., Mattson, M. P., & Maudsley, S. (2005). Class II G protein-coupled receptors and their ligands in neuronal function and protection. Neuromolecular medicine, 7(1-2), 3–36. https://doi.org/10.1385/nmm:7:1-2:003 Newton, A. C., Bootman, M. D., & Scott, J. D. (2016). Second Messengers. Cold Spring Harbor perspectives in biology, 8(8), a005926. https://doi.org/10.1101/cshperspect.a005926 Khorram, O., Laughlin, G. A., & Yen, S. S. (1997). Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. The Journal of clinical endocrinology and metabolism, 82(5), 1472–1479. https://doi.org/10.1210/jcem.82.5.3943 Ito T, Igarashi H, Pradhan TK, Hou W, Mantey SA, Taylor JE, Murphy WA, Coy DH, Jensen RT. GI side-effects of a possible therapeutic GRF analogue in monkeys are likely due to VIP receptor agonist activity. Peptides. 2001 Jul;22(7):1139-51. https://pubmed.ncbi.nlm.nih.gov/11445245/ Schally AV, Zhang X, Cai R, Hare JM, Granata R, Bartoli M. Actions and Potential Therapeutic Applications of Growth Hormone-Releasing Hormone Agonists. Endocrinology. 2019 Jul 1;160(7):1600-1612. https://pubmed.ncbi.nlm.nih.gov/31070727/ Sinha, D. K., Balasubramanian, A., Tatem, A. J., Rivera-Mirabal, J., Yu, J., Kovac, J., Pastuszak, A. W., & Lipshultz, L. I. (2020). Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Translational andrology and urology, 9(Suppl 2), S149–S159. https://doi.org/10.21037/tau.2019.11.30 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.
ARA-290 (16mg)
ARA-290 peptide, also known as cibinetide and helix B surface peptide (HBSP) in scientific literature, is an 11 amino acid chain derived from the beta domain of the naturally-occurring protein erythropoietin (EPO). This part of the EPO sequence is considered to assist in tissue regeneration and repair without exerting stimulus on the production of red blood cells.(1) Scientists consider the primary function of the EPO is to stimulate tissues to produce red blood cells. Still, the beta domain of the protein, and consequently ARA-290, do not appear to possess this property. Instead, they may possess certain potential regenerative, anti-inflammatory, anti-nociceptive, and other lesser-known properties of the original naturally occurring EPO protein. Overview Scientific findings(2) thus far suggest that once a tissue undergoes an injury, a tissue-protective receptor (TPR) pathway may be activated. This TPR receptor mainly consists of a beta receptor unit (CD131) and a subunit from the EPO receptor, jointly called the innate repair receptor. Researchers have suggested that the ARA-290 peptide molecule may bind to this innate repair receptor and possibly attenuate nerve and allodynia-led pain (nociception).(3) It is also suggested that the ARA-290 peptide may act primarily via this IRR-mediated pathway. Chemical Makeup Molecular Formula: C51H54N16O21 Molecular Weight: 1257.3 g/mol Other Known Titles: PH-BSP Research and Clinical Studies ARA-290 Peptide and Nociception Scientists consider that Transient Receptor Potential (TRP) channels may be the primary nociceptive stimulating channels, including possible thermal, chemical, and mechanical stimuli. In the presence of such a causative agent, one of the TRP channels, namely TRPV1, may be triggered. Upon activation, it might induce the ejection of neuropeptides, which then are considered to generate action potential in the nervous systems. This action potential is referred to as "nociception."(4) A 2016 study(5) suggested that ARA-290 peptide may have the potential to increase the threshold of this TRPV1 channel, with researchers further implying that the peptide might inhibit the TRPV1 actions and thereby no neuropeptides will be released to spark a nociceptive response. The researchers conducted a study with a C57/BL6 strain of murine models to investigate this hypothesis. They took neurons from two areas of the murine nervous system, the dorsal root ganglion, and the trigeminal ganglion, and studied them using calcium imaging. This involved the introduction of a special dye to the cells that lights up when calcium is present and then examining them under a special microscope. The experiment measured how these neurons potentially reacted to three substances: ARA-290, capsaicin (the compound that makes chili peppers hot), and KCl (a common chemical compound that can be used as a control). The researchers were particularly interested in whether ARA-290 could reduce the reaction of the neurons to capsaicin. They also did some direct tests on the murine models. One test measured how potentially sensitive the murine models' appendages were to nociception. They used different concentrations of ARA-290 or a control solution on the murine models' hind appendages. Then, they exposed them to capsaicin to see if it made them potentially more sensitive to nociception. They used a tool to apply pressure to the appendages and measured the point at which the murine models pulled their appendages away. Another test checked how often the murine models withdrew their appendages over 24 hours after exposure to capsaicin. Here, the researchers were evaluating whether giving the murine models ARA-290 after the capsaicin may have affected their sensitivity to nociception. Thus, the findings suggested that ARA-290 might specifically block the reaction of neurons to capsaicin without affecting other types of heat sensors. This may suggest that ARA-290 targets specifically the TRPV1 channels and might potentially increase the amount of capsaicin needed to activate these channels. ARA-290 is still being actively studied for its possible role in nociception "mitigation". However, researchers have also developed hypotheses about its other potential mechanisms of action, such as potential anti-inflammatory and possible immunomodulatory impact. ARA-290 Peptide and Retinal Ischemia A recent study(6) has suggested that ARA-290 may have the potential to protect the endothelial blood vessels and possibly thereby combat retinal ischemia in models of ischemic retinopathies. A possible mitigation method for retinal ischemia is the restoration of endothelial colony-forming cells (ECFC) in the retinal tissue. This study explored the potential of ARA-290 in reducing the current pro-inflammatory conditions in the ischemic retina and its potential effects on vascular regeneration aided by ECFCs. Experimental murine models induced with retinal ischemia underwent ECFC cell transplantation for this study. To determine the potential of the peptide, transplantation in some murine models occurred in the presence of ARA-290 while the rest was in the absence of peptides. Experimental investigations were conducted to assess the impact of ARA-290 on the survival mechanisms and functionality within ECFC (Endothelial Colony-Forming Cell) cultures. The research suggested that ARA-290 might potentially initiate survival pathways and improve cell survival in ECFCs under oxidative stress caused by H2O2. The study aimed to determine the effectiveness of ECFC transplantation in promoting vascular repair in the retinal area of mice, utilizing the oxygen-induced retinopathy (OIR) model for this purpose. The research compared the effects of transplanting ECFCs with and without ARA-290. Additionally, the study examined the inflammatory cytokine profile and microglia activation, which may act as markers of inflammation. Preliminary results indicated that introducing ECFCs with EPO or ARA-290 before transplantation did not appear to significantly enhance their ability to repair blood vessels in the ischemic retina. However, the systemic introduction of ARA-290 in OIR mice seemed to lower the levels of pro-inflammatory cytokines like IL-1β and TNF-α in the retinal tissue, hinting at its possible anti-inflammatory properties. The introduction of ECFCs into the vitreous humor of the eye led to their integration into the impaired retinal blood vessels and seemed to notably reduce the area without blood vessels. Notably, ARA-290 appeared to enhance the vaso-reparative capacity of the ECFCs, a result not observed with EPO. After the study, it was suggested by the researchers that the peptide exhibited a reduction in the inflammatory expression of interleukin cells in the retina. The scientists commented that: “regulation of the pro-inflammatory milieu of the ischemic retina can be enhanced by ARA290 and may be a useful [research agent] to ECFC-based cell [procedures] for ischemic retinopathies.” ARA-290 Peptide and Inflammatory Cytokine Cells One study(7) was conducted to determine whether the erythropoietin analog, ARA-290 peptide, may possess anti-inflammatory and cell protective potential. More specifically, the researchers investigated the potential of the peptide in pancreatic islet transplantation (PITx) models, which typically demonstrates limited success due to islet damage that occurs during isolation and from the severe inflammatory reactions caused by the transplantation procedure. In this study,(7) experimental murine models, which underwent transplantation intervention for 180+ pancreatic islet cells, were used. The murine models were introduced to the ARA-290 peptide right before, at 0, 6, and 24 hours after intervention. After 12 hours of peptide presence, the liver samples from the murine models were collected and analyzed. Peptide cells appeared to exhibit minimal damage to the islets. The researchers indicated that the peptide may have protected the islet cells from cytokines and subsequent apoptosis. More precisely, the scientists commented that “ARA-290 protected islets from cytokine-induced damage and apoptosis. Secretion of pro-inflammatory cytokines (IL-6, IL-12, and TNF-α) from macrophages was significantly inhibited by ARA-290.” The findings indicated that ARA-290 might potentially maintain the functionality of cultured islets under the stress of proinflammatory cytokines. This hypothesis is supported by observed reductions in caspase 3/7 activity, suggesting a protective effect against apoptosis triggered by cytokines. Additionally, ARA-290 appeared to diminish the production of proinflammatory cytokines in the liver following pancreatic islet transplantation, hinting at its possible role in mitigating inflammatory responses within the liver. Further delving into ARA-290's potential mode of action, it is believed to engage the EPOR-βcR complex, apparently initiating a cascade of signaling events. EPOR-βcR is a complex formed by the erythropoietin receptor (EPOR) and the beta-common receptor (βcR). It plays a key role in cellular signaling, particularly in response to certain growth factors and cytokines. These events might inhibit the transcription of proinflammatory genes and promote cellular survival. It is theorized that this process could involve the activation of the PI3K-Akt and JAK2-STAT5 pathways (pathways with essential roles in cell growth, survival, and metabolism), along with a reduction in NF-κB-mediated gene transcription (proinflammatory pathways that can lead to cell damage and death). ARA-290's interaction with the heightened EPOR-βcR complex typically upregulated in response to cell or tissue damage, is also of interest. Ultimately, the scientists commented that “ARA 290 protected pancreatic islets from cytokine-induced damage and apoptosis and ameliorated the inflammatory response” in these experimental models. Thus, the researchers concluded that this interaction may potentially shield islets against the detrimental effects of proinflammatory cytokines, which might be released by activated macrophages or as a result of the transplantation procedure itself. ARA-290 Peptide and Tissue Protection Based on the available research(8), the ARA-290 peptide is considered to have potential binding capacity to TPRs, which may assist in maintaining the function of the tissues protecting against harmful inflammation and subsequent cellular and tissue death. Researchers have posited the main potential of ARA-290 peptide over the endogenous erythropoietin cells to bind TPR receptor cells without further cardiovascular or muscular impact.(8) This potential of the peptide may help improve tissue regeneration and reduce tissue damage, possibly promoting better wound recovery and healing and decreasing the formation of scars in experimental murine models. ARA-290 Peptide and Immunomodulation via TPR Pathway Scientists posit that the TPR pathway, once stimulated, may express on various immunological cells, including macrophages. With the potential of ARA-290 peptide to bind with the TPR receptor cells, it may restrict the release of certain inflammatory molecules such as interleukin-6 (IL-6). Owing to a reduced secretion, it may lead to reduced severity of immuno-compromising conditions. (8) ARA-290 Peptide and Immunomodulation via Adaptive Immunity Research(8) has suggested that ARA-290 peptide may potentially alter the presentation of antigens by the dendritic cells, thereby possibly altering adaptive immunity in test models. Owing to the peptide's potential to "fine tune" the immune cells, they may not reject transplanted bodies, potentially leading to successful transplantation experiments in laboratory models. ARA-290 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering. References: What is Erythropoietin? Home Health Network. https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/erythropoietin Brines M, Cerami A. The receptor that tames the innate immune response. Mol Med. 2012 May 9;18(1):486-96. https://pubmed.ncbi.nlm.nih.gov/22183892/ Dahan, A., Dunne, A., Swartjes, M., Proto, P. L., Heij, L., Vogels, O., van Velzen, M., Sarton, E., Niesters, M., Tannemaat, M. R., Cerami, A., & Brines, M. (2013). ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Molecular medicine (Cambridge, Mass.), 19(1), 334–345. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883966/ Jara-Oseguera, A., Simon, S. A., & Rosenbaum, T. (2008). TRPV1: on the road to pain relief. Current molecular pharmacology, 1(3), 255–269. https://doi.org/10.2174/1874467210801030255 Zhang W, Yu G, Zhang M. ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception. Peptides. 2016 Feb;76:73-9. https://pubmed.ncbi.nlm.nih.gov/26774587/ O'Leary OE, Canning P, Reid E, Bertelli PM, McKeown S, Brines M, Cerami A, Du X, Xu H, Chen M, Dutton L, Brazil DP, Medina RJ, Stitt AW. The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic. Exp Eye Res. 2019 May;182:144-155. https://pubmed.ncbi.nlm.nih.gov/30876881/ Watanabe M, Lundgren T, Saito Y, Cerami A, Brines M, Östenson CG, Kumagai-Braesch M. A Nonhematopoietic Erythropoietin Analogue, ARA 290, Inhibits Macrophage Activation and Prevents Damage to Transplanted Islets. Transplantation. 2016 Mar;100(3):554-62. https://pubmed.ncbi.nlm.nih.gov/26683514/ Peng, B., Kong, G., Yang, C. et al. Erythropoietin and its derivatives: from tissue protection to immune regulation. Cell Death Dis 11, 79 (2020). https://doi.org/10.1038/s41419-020-2276-8 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.