Modified GRF (1-29) is a peptide hormone that is also known as CJC-1295 without DAC (Drug Affinity Complex). It is a synthetic analog of growth hormone-releasing hormone (GHRH) and is designed to increase natural production of growth hormone. Similarly to other GHRH analogs, it appears to work by binding to the growth hormone-releasing hormone receptor in the pituitary gland, and stimulating the release of growth hormone (HGH). Modified GRF (1-29) has been studied for its potential action in research on various conditions, including growth hormone deficiency, osteoporosis, and muscle wasting.

 

Overview of Modified GRF (1-29)

Modified GRF (1-29) is a modified version of GRF (1-29), the smallest amino-acid sequence from the original GHRH that may still retain the ability to trigger the receptors in the pituitary gland and induce an hGH spike. As the name suggests, GRF (1-29) and modified GRF (1-29) are made of 29 amino acids. However, Modified GRF (1-29) has 4 of the original 29 amino acids replaced with the intention to make the peptide more resistant to rapid cleavage by the enzyme dipeptidyl peptidase-4. This cleavage was previously reported to result in peptide inactivation.^[1] More specifically, the replaced amino acids are the 2nd, 8th, 15th, and 27th amino acids.

Due to this replacement, the peptide is also known as tetrasubstituted GRF (1-29), and its sequence is Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg. As a result, the half-life of the peptide has been anticipated to last from 10 – 30 mins.  One of the main modifications is the replacement of L-alanine with D-alanine in the 2nd spot.^[2] According to the researchers, “the disappearance half-time of the D-Ala2 analog was 6.7 +/- 0.5, whereas that of GHRH-(1-29)-NH2 was 4.3 +/- 1.4 min (P < 0.05). These findings [suggest] that the D-Ala2 substitution contributes to the enhancement of biological activity by reducing metabolic clearance.“

 

Modified GRF (1-29) and Growth Hormone Synthesis

Modified GRF (1-29) was developed to have a longer half-life but retain identical potential to GRF (1-29), also known as Sermorelin. Since no studies investigate the effects of Modified GRF (1-29) without DAC, the following reports will be based on GRF (1-29) research. Researchers have reported GRF (1-29) to have the potential to increase HGH pulse synthesis.^[3] Repeated dosing may lead to a significant increase in growth hormone levels.

A study investigating the action of Modified GRF (1-29) found that it might lead to significant improvements in muscular contractile force.^[8] Decline and alterations in muscle mass may result in decreased mobility, and interventions such as GRF (1-29) therapy may potentially mitigate the rapidity or onset of muscular atrophy. Another growth hormone-related impact may be the promotion of skin cell proliferation and increased collagen deposition within the derma.

 

Modified GRF (1-29) and Composition

One study focused on the impact of Modified GRF (1-29) exposure reported the peptide’s potential to increase growth velocity by 74%, maintained for up to a year of exposure studies.^[4] Further studies suggest that exposure to GRF (1-29) for a duration of 4 months resulted in a significant increase in lean body mass. However, it is important to note that such effects were only observed in male research models and were not observed in females.^[5] This could be attributed to the fact that GRF (1-29) may not cause growth hormone (hGH) peaks to exceed the physiological limits, which may differ between genders due to biological variations. For example, as the growth hormone remains within its physiological limits in female organisms, it may still significantly be impacted by the negative action of estrogens on IGF-1 production, the main anabolic mediator of hGH.^[6] Researchers reported that estrogen appears to impact the HGH-IGF-1 axis “by decreasing liver secretion of insulin-like growth factor-I (IGF-I).“^[7]

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

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1. Scarborough R, Gulyas J, Schally AV, Reeves JJ. Analogs of growth hormone-releasing hormone induce release of growth hormone in the bovine. J Anim Sci. 1988 Jun;66(6):1386-92. doi: 10.2527/jas1988.6661386x. PMID: 3135287.
2. Soule S, King JA, Millar RP. Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. J Clin Endocrinol Metab. 1994 Oct;79(4):1208-11. doi: 10.1210/jcem.79.4.7962295. PMID: 7962295.
3. Achermann JC, Hindmarsh PC, Robinson IC, Matthews DR, Brook CG. The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals. Clin Endocrinol (Oxf). 1999 Nov;51(5):575-85. doi: 10.1046/j.1365-2265.1999.00839.x. PMID: 10594518.
4. Thorner M, Rochiccioli P, Colle M, Lanes R, Grunt J, Galazka A, Landy H, Eengrand P, Shah S. Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group. J Clin Endocrinol Metab. 1996 Mar;81(3):1189-96. doi: 10.1210/jcem.81.3.8772599. PMID: 8772599.
5. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997 May;82(5):1472-9. doi: 10.1210/jcem.82.5.3943. PMID: 9141536.
6. Cook DM. Growth hormone and estrogen: a clinician’s approach. J Pediatr Endocrinol Metab. 2004 Sep;17 Suppl 4:1273-6. PMID: 15506073.
7. Corpas E, Harman SM, Piñeyro MA, Roberson R, Blackman MR. Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab. 1992 Aug;75(2):530-5. doi: 10.1210/jcem.75.2.1379256. PMID: 1379256.
8. Vittone J, Blackman MR, Busby-Whitehead J, Tsiao C, Stewart KJ, Tobin J, Stevens T, Bellantoni MF, Rogers MA, Baumann G, Roth J, Harman SM, Spencer RG. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. 1997 Jan;46(1):89-96. doi: 10.1016/s0026-0495(97)90174-8. PMID: 9005976.
9. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997 May;82(5):1472-9. doi: 10.1210/jcem.82.5.3943. PMID: 9141536.

ARA-290 peptide is a small, synthetic peptide is a derivative of erythropoietin (EPO), a hormone that is considered to stimulate the production of red blood cells. However, unlike EPO, ARA-290 does not appear to affect erythropoiesis and has been suggested to exhibit tissue-protective characteristics. In this article, we will explore what ARA-290 peptide is, how it works, and its potential research applications.

 

ARA-290 Peptide Overview

ARA-290 is a synthetic peptide first developed by a research team led by Dr. Schmidt at the New York University School of Medicine. The team discovered the innate repair receptor and suggested that activating it with a synthetic peptide may improve tissue repair and reduce inflammation in various animal disease models.

After further testing and refinement, they developed ARA-290 peptide as a potential agent within the context of research in various conditions involving tissue damage, inflammation, and neuropathic pain. It consists of 11 amino acids designed to mimic a specific sequence of erythropoietin. The amino acid sequence of ARA-290 peptide is Tyr-Glu-Pro-Pro-Pro-Tyr-Gly-Gly-Lys-Pro-Ala

This sequence was identified as the “receptor-specific” site of erythropoietin (EPO), which interacts with a specific receptor on the surface of cells to elicit tissue-protective effects. ARA-290 peptide was developed to specifically target this receptor and avoid interactions with the EPO receptor, which is responsible for the hormone’s potential on erythropoiesis.

 

ARA-290 Studies on Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain

Sarcoidosis-associated small nerve fiber loss and damage (SNFLD) refers to a condition in which the small nerve fibers in the peripheral nervous system are damaged or lost due to sarcoidosis. These are the fibers responsible for transmitting sensory information, such as pain, temperature, and touch. Sarcoidosis is a systemic autoimmune inflammatory disease that may affect multiple organs, including the nerves. It appears to lead to the formation of tiny clusters of inflammatory cells called granulomas, which can cause tissue damage and organ dysfunction.

ARA-290 peptide was hypothesized to reduce symptoms in animal neuropathy models, which led to investigating its potential in research of neuropathy due to Sarcoidosis-associated SNFLD.^[1] According to the research, these potential actions may likely be due to the anti-inflammatory characteristics of the peptide that it may potentially exert in nervous tissues. The scientists concluded that “ARA290 … reduced allodynia coupled to suppression of the spinal microglia response, suggestive of a mechanistic link between ARA290-induced suppression of central inflammation and relief of neuropathic pain symptoms.”^[2]

 

ARA-290 Peptide and Diabetes and Related Complications

Insulin resistance plays a significant role in the development and progression of type 2 diabetes. Preliminary research on the glycemic and metabolic potential of ARA-290 peptide was conducted in mice models of insulin resistance, hyperlipidemia, hepatic lipid accumulation, and impaired insulin signaling pathways in skeletal muscle.^[5] A high-fat, high-sucrose diet-induced the condition, and exposure to ARA-290 peptide appeared to reduce hepatic lipid deposition and normalized serum glucose and lipid profiles. In this murine model, the exposure appeared to improve insulin sensitivity and glucose uptake in skeletal muscle, attenuate the overproduction of myokines, and enhance mitochondrial biogenesis in skeletal muscle. Many other animal studies also report that ARA-290 peptide may significantly improve glycemic control and lower insulin resistance in rats with type 2 diabetes.^[6]

Further studies also report similar results in models of diabetes. According to one study of various diabetes models (mainly type 2 diabetes) and diabetic macular edema (DME), 12 weeks of ARA-290 peptide exposure appeared to lead to improvements in central subfield retinal thickness, tear production, diabetic control, and albuminuria.^[7]

Another study included research models of type 2 diabetes who received ARA-290 peptide or a placebo for 28 days and were examined for a month following discontinuation.^[8] The researchers suggested that ARA-290 appeared to exhibit an improvement in HbA1c and lipid profiles. They noted that “subjects receiving ARA 290 exhibited an improvement in hemoglobin A1c (Hb A1c) and lipid profiles throughout the 56 [day] observation period.” Neuropathic symptoms and mean corneal nerve fiber density also appeared to improve in the ARA-290 peptide group.

 

ARA-290 Peptide and Inflammation, Cell Aging

Studies have suggested that ARA-290 peptide may reduce inflammation by modulating the activity of the innate immune system, which is considered responsible for the initial response to infections and tissue damage. Specifically, ARA-290 peptide has been suggested to inhibit the activation of macrophages and reduce the production of pro-inflammatory cytokines, such as TNF-alpha and IL-1beta, in models of colon inflammation.^[9]

One trial in aged rats reports that chronic ARA-290 peptide exposure may possibly reduce inflammation and fibrosis in the heart, improve mitochondrial and myocardial cell function, and preserve left ventricular ejection fraction.^[10] ARA-290 also apparently mitigated the age-associated increase in blood pressure, preserved body weight, and reduced markers of organism-wide frailty.

 

Conclusion

More research is needed to fully understand ARA-290’s potential.  Currently, the peptide has research-only status, and it is not intended for  managing any condition.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

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1. Swartjes M, van Velzen M, Niesters M, Aarts L, Brines M, Dunne A, Cerami A, Dahan A. ARA 290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain coupled with suppression of the spinal microglia response. Mol Pain. 2014 Feb 16;10:13. doi: 10.1186/1744-8069-10-13. PMID: 24529189; PMCID: PMC3928087.
2. Dahan A, Dunne A, Swartjes M, Proto PL, Heij L, Vogels O, van Velzen M, Sarton E, Niesters M, Tannemaat MR, Cerami A, Brines M. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med. 2013 Nov 8;19(1):334-45. doi: 10.2119/molmed.2013.00122. Erratum in: Mol Med. 2016 Oct 20;22:674. PMID: 24136731; PMCID: PMC3883966.
3. Culver DA, Dahan A, Bajorunas D, Jeziorska M, van Velzen M, Aarts LPHJ, Tavee J, Tannemaat MR, Dunne AN, Kirk RI, Petropoulos IN, Cerami A, Malik RA, Brines M. Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain. Invest Ophthalmol Vis Sci. 2017 May 1;58(6):BIO52-BIO60. doi: 10.1167/iovs.16-21291. PMID: 28475703.
4. Heij L, Niesters M, Swartjes M, Hoitsma E, Drent M, Dunne A, Grutters JC, Vogels O, Brines M, Cerami A, Dahan A. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med. 2012 Nov 15;18(1):1430-6. doi: 10.2119/molmed.2012.00332. PMID: 23168581; PMCID: PMC3563705.
5. Collino M, Benetti E, Rogazzo M, Chiazza F, Mastrocola R, Nigro D, Cutrin JC, Aragno M, Fantozzi R, Minetto MA, Thiemermann C. A non-erythropoietic peptide derivative of erythropoietin decreases susceptibility to diet-induced insulin resistance in mice. Br J Pharmacol. 2014 Dec;171(24):5802-15. doi: 10.1111/bph.12888. Epub 2014 Nov 24. PMID: 25164531; PMCID: PMC4290718.
6. Muller C, Yassin K, Li LS, Palmblad M, Efendic S, Berggren PO, Cerami A, Brines M, Östenson CG. ARA290 Improves Insulin Release and Glucose Tolerance in Type 2 Diabetic Goto-Kakizaki Rats. Mol Med. 2016 May;21(1):969-978. doi: 10.2119/molmed.2015.00267. Epub 2015 Dec 29. PMID: 26736179; PMCID: PMC4818260.
7. Lois N, Gardner E, McFarland M, Armstrong D, McNally C, Lavery NJ, Campbell C, Kirk RI, Bajorunas D, Dunne A, Cerami A, Brines M. A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema. J Clin Med. 2020 Jul 14;9(7):2225. doi: 10.3390/jcm9072225. PMID: 32674280; PMCID: PMC7408632.
8. Brines M, Dunne AN, van Velzen M, Proto PL, Ostenson CG, Kirk RI, Petropoulos IN, Javed S, Malik RA, Cerami A, Dahan A. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Mol Med. 2015 Mar 13;20(1):658-66. doi: 10.2119/molmed.2014.00215. PMID: 25387363; PMCID: PMC4365069.
9. Nairz M, Haschka D, Dichtl S, Sonnweber T, Schroll A, Aßhoff M, Mindur JE, Moser PL, Wolf D, Swirski FK, Theurl I, Cerami A, Brines M, Weiss G. Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis. Sci Rep. 2017 Oct 12;7(1):13012. doi: 10.1038/s41598-017-13046-3. PMID: 29026145; PMCID: PMC5638901.
10. Winicki NM, Nanavati AP, Morrell CH, Moen JM, Axsom JE, Krawczyk M, Petrashevskaya NN, Beyman MG, Ramirez C, Alfaras I, Mitchell SJ, Juhaszova M, Riordon DR, Wang M, Zhang J, Cerami A, Brines M, Sollott SJ, de Cabo R, Lakatta EG. A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan. Front Cardiovasc Med. 2023 Jan 18;9:1096887. doi: 10.3389/fcvm.2022.1096887. PMID: 36741836; PMCID: PMC9889362.

Sermorelin Acetate, a synthetic peptide, was developed to function as an analog of a naturally occurring hormone called growth hormone-releasing hormone (GHRH). While GHRH has 44 amino acids, Sermorelin peptide is truncated down to 29 amino acids. Sermorelin peptide is also known as the Growth Hormone Releasing Factor (1-29) or GRF (1-29). Sermorelin is the smallest fragment of the GHRH chain that appears to possess the same functions, namely, stimulating the pulsatile release of growth hormone (HGH) by the pituitary gland. Due to this potential, Sermorelin peptide has been classified by researchers as a Growth Hormone Secretagogue (GHS). Like GHRH and other GHSs, Sermorelin may possibly increase the production of HGH in the pituitary gland, resulting in higher and more frequent peaks of the growth hormones. This would also result in elevated levels of Insulin Growth Factor-1 (IGF-1), a primary anabolic mediator.

 

What is the Sermorelin?

Sermorelin was first synthesized in the early 1980s and has been avidly researched since its development. It is made of 29 amino acids and bears the sequence YADAXFXNSYRKVLGQLSARKLLQDXMSR. Sermorelin peptide, aka GRF (1-29), should not be confused with Modified GRF (1-29), which has 4 of the original 29 amino acids replaced with the intent to increase its half-life from 10 to 30 minutes.

 

General Research in Sermorelin

 

Sermorelin Peptide and the Endocrine System

As a GHRH analog, Sermorelin peptide has been researched primarily for its potential to stimulate pulsatile hGH synthesis via the pituitary gland. Studies observed that as long as the pituitary gland is functioning correctly, Sermorelin, combined with the amino acid Arginine, may induce a significant spike in serum HGH levels.^[1] Studies in research models of growth failure also report that Sermorelin peptide appeared to increase growth velocity with growth failure and functional pituitary glands by 74%.^[2] Further research reported that 6 months of either Sermorelin peptide or hGH exposure, appeared to exhibit a similar increase in growth velocity.^[3] Studies also reported an apparent significant increase in serum HGH levels after several days of Sermorelin peptide introduction.^[4]

The peptide may also affect the levels of other hormones apart from HGH, such as insulin and sex hormones.  Although high hGH is often associated with increased insulin levels and insulin resistance, one 16-week trial suggested that Sermorelin may improve insulin sensitivity in males but not in female organisms.^[5]  One animal trial reported an increase in gonadotropic hormones and testosterone levels in male mice, but there is no clinical research to support these findings.^[6]

 

Sermorelin Studies in Cardiovascular Function

Sermorelin may impact cardiovascular functioning due to its apparent HGH-stimulating potential.^[7] Researchers suggest, “That GHRH analog [exposure] induced anabolic effects favoring [male species] more than [female]. Further studies are needed to define the gender differences observed in response to GHRH analog [exposure].”^[8]

 

Sermorelin Peptide and Extracellular Matrix

Scientists posit that Sermorelin has the potential to function in increasing HGH levels. From this assumption, it may be possible for Sermorelin peptide to increase the proliferation of new skin cells, ultimately leading to increased collagen deposition inside the derma.

One study focusing on male species reported that 4 months of Sermorelin peptide exposure appeared to significantly increase their skin thickness.^[11] Additionally, the males, but not the female organisms, also expressed increased libido and related behaviors.

 

Sermorelin Peptide and the Nervous System

One study suggested that even a one-time exposure to Sermorelin peptide may support improvements in short-term memory.^[12] In fact, researchers reported that the effect on memory recall appeared more significant in Sermorelin-exposed research models than those given a placebo. There is also mixed data regarding the potential of Sermorelin peptide on brain tumors. One experiment reports that Sermorelin peptide may speed up the development of neuroendocrine tumors such as pituitary adenomas due to its possible growth-promoting effect.^[13] However, a study in gliomas reported the opposite effect, observing that the peptide appeared to suppress the recurrence of the tumors.^[14]

 

Conclusion

Sermorelin may hold significant research potential as a Growth Hormone Secretagogue (GSH). This is supported by research findings indicating that when exposed to Sermorelin, animal research models’ serum growth hormone levels might not exceed the physiological limits exerted by somatostatin.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

---

1. Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs. 1999 Aug;12(2):139-57. doi: 10.2165/00063030-199912020-00007. PMID: 18031173.
2. Thorner M, Rochiccioli P, Colle M, Lanes R, Grunt J, Galazka A, Landy H, Eengrand P, Shah S. Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group. J Clin Endocrinol Metab. 1996 Mar;81(3):1189-96. doi: 10.1210/jcem.81.3.8772599. PMID: 8772599.
3. Neyzi O, Yordam N, Ocal G, Bundak R, Darendeliler F, Açikgöz E, Berberoğlu M, Günöz H, Saka N, Calikoğlu AS. Growth response to growth hormone-releasing hormone(1-29)-NH2 compared with growth hormone. Acta Paediatr Suppl. 1993 Mar;388:16-21; discussion 22. doi: 10.1111/j.1651-2227.1993.tb12828.x. PMID: 8329826.
4. Achermann JC, Hindmarsh PC, Robinson IC, Matthews DR, Brook CG. The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals. Clin Endocrinol (Oxf). 1999 Nov;51(5):575-85. doi: 10.1046/j.1365-2265.1999.00839.x. PMID: 10594518.
5. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997 May;82(5):1472-9. doi: 10.1210/jcem.82.5.3943. PMID: 9141536.
6. Chatelain PG, Sanchez P, Saez JM. Growth hormone and insulin-like growth factor I treatment increase testicular luteinizing hormone receptors and steroidogenic responsiveness of growth hormone deficient dwarf mice. Endocrinology. 1991 Apr;128(4):1857-62. doi: 10.1210/endo-128-4-1857. PMID: 2004605.
7. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997 May;82(5):1472-9. doi: 10.1210/jcem.82.5.3943. PMID: 9141536.
8. Vittone J, Blackman MR, Busby-Whitehead J, Tsiao C, Stewart KJ, Tobin J, Stevens T, Bellantoni MF, Rogers MA, Baumann G, Roth J, Harman SM, Spencer RG. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. 1997 Jan;46(1):89-96. doi: 10.1016/s0026-0495(97)90174-8. PMID: 9005976.
9. Corpas E, Harman SM, Piñeyro MA, Roberson R, Blackman MR. Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab. 1992 Aug;75(2):530-5. doi: 10.1210/jcem.75.2.1379256. PMID: 1379256.
10. Vittone J, Blackman MR, Busby-Whitehead J, Tsiao C, Stewart KJ, Tobin J, Stevens T, Bellantoni MF, Rogers MA, Baumann G, Roth J, Harman SM, Spencer RG. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. 1997 Jan;46(1):89-96. doi: 10.1016/s0026-0495(97)90174-8. PMID: 9005976.
11. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997 May;82(5):1472-9. doi: 10.1210/jcem.82.5.3943. PMID: 9141536.
12. Alvarez XA, Cacabelos R. Effects of GRF (1-29) NH2 on short-term memory: neuroendocrine and neuropsychological assessment in healthy young subjects. Methods Find Exp Clin Pharmacol. 1990 Sep;12(7):493-9. PMID: 2087150.
13. Stepień T, Sacewicz M, Lawnicka H, Krupiński R, Komorowski J, Siejka A, Stepień H. Stimulatory effect of growth hormone-releasing hormone (GHRH(1-29)NH2) on the proliferation, VEGF and chromogranin A secretion by human neuroendocrine tumor cell line NCI-H727 in vitro. Neuropeptides. 2009 Oct;43(5):397-400. doi: 10.1016/j.npep.2009.08.005. Epub 2009 Sep 10. PMID: 19747727.
14. Chang Y, Huang R, Zhai Y, Huang L, Feng Y, Wang D, Chai R, Zhang W, Hu H. A potentially effective drug for patients with recurrent glioma: sermorelin. Ann Transl Med. 2021 Mar;9(5):406. doi: 10.21037/atm-20-6561. PMID: 33842627; PMCID: PMC8033379.

Peptides consist of chains of amino acids that may play a crucial role in many biological processes. One such peptide, MOTS-c (mitochondrial ORF of the 12S rRNA type-c), has recently emerged, found in mitochondria, which is considered the powerhouse of the cell.

This peptide is encoded in the mitochondrial genome and appears to be able to regulate nuclear gene expression in the mitochondria in response to various factors, such as metabolic stress. Laboratory experiments suggest that it may have anti-cell aging, anti-inflammatory and metabolic characteristics, though these are research hypotheses. The potential of MOTS-c has yet to be thoroughly studied, and further research is needed to determine the whole spectrum of its action.

 

MOTS-c Peptide Overview

MOTS-c is a naturally produced component of mitochondria, the cellular organelles responsible for producing energy. The structure of the peptide consists of 16 amino acids and bears the sequence H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH.

Preliminary research investigates its potential spectrum of action.^[1] The studies report, “Under stress conditions, MOTS-c translocates to the nucleus where it regulates a wide range of genes in response to metabolic dysfunction.” Thus, MOTS-c is thought to regulate energy metabolism and may have anti-inflammatory and anti-cell aging characteristics.

 

MOTS-c Research in Insulin Resistance, Metabolism, and Muscle

One of the most actively researched potentials of MOTS-c is its action on insulin resistance and metabolic function. Several animal studies suggest MOTS-c may help improve glucose metabolism in metabolic disorders such as insulin resistance by targeting skeletal muscles.^[2] This mechanism of action may work by enhancing glucose uptake by skeletal muscles and may also helps decrease levels of visceral fat.

One of these studies reports that MOTS-c targets the skeletal muscle and inhibits the folate cycle and its tethered de novo purine biosynthesis, leading to AMPK pathway activation.^[3] As a result, MOTS-c exposure in mice appeared to mitigate age-dependent and high-fat-diet-induced insulin resistance and diet-induced obesity.

MOTS-c may also help improve metabolic function by stimulating the “browning” of white (beige) fat and increasing thermogenesis in fat tissue.^[4] These potential actions of MOTS-c are believed to be mediated by the activation of the ERK signaling pathway.

MOTS-c has also shown promise in studies in gestational diabetes, a type of diabetes that occurs due to increased insulin resistance in pregnancy.^[5] In a GDM mouse model, daily exposure to MOTS-c during pregnancy appeared to significantly reduce hyperglycemia, improve insulin sensitivity and glucose tolerance, and reduce birth weight and risk of offspring death.

The action of MOTS-c on skeletal muscles do not appear to be limited to improving their glucose uptake. Animal research also suggests that the peptide has the potential to impact muscle atrophy in obesity and type 2 diabetes.^[6] MOTS-c appears to function by decreasing myostatin levels in plasma in mice and elevating AKT phosphorylation, which inhibits the activity of FOXO1, a transcription factor for muscle-wasting genes. It may also potentially reduce dystrophic muscle atrophy, specifically in Duchenne Muscular Dystrophy (DMD) models.^[7]

 

MOTS-c Peptide and the Heart

MOTS-c peptides may exert a protective action on the heart muscle due to improved mitochondria function in the myocytes. According to one study in a murine model of heart failure, the peptide appeared to reduce the inflammation response and improve cardiac function.^[8] The peptide also appeared to activate the AMPK pathway, reduce cell apoptosis, and improve the antioxidant capacity in the heart of the mice.

MOTS-c may also help reduce certain adverse actions of type 2 diabetes on the heart, as studies in diabetic rats suggested that peptide exposure appeared to result in improved myocardial mitochondrial damage, preserve cardiac systolic and diastolic function, and altered 47 disease-causing genes related to apoptosis, immunoregulation, angiogenesis, and fatty acid metabolism.^[9]

Thanks to the activation of the AMPK and the anti-oxidative potential of the peptide, animal studies also suggest it may help reduce inflammation in the heart and protect against vascular calcification (VC), which is a complication of atherosclerosis.^[10][11]

Researchers report that MOTS-c may also improve mechanical heart efficiency, enhance heart systolic function, and show a tendency to improve diastolic function in mice.^[12] These results suggest that MOTS-c might help to optimize the cardiovascular function. Scientists also suggest that MOTS-c may have heart function action similar to physical stimulation via activating the NRG1-ErbB4-C/EBPβ pathway.^[13]

 

MOTS-c Peptide and Bone

By activating the phosphorylated AMPK, MOTS-c may provide positive impacts on bones. One study reports that in a murine model of osteoporosis, MOTS-c exposure appeared to inhibit osteoclast differentiation and reduce bone loss, as determined by micro-CT examination.^[14] The scientists concluded that “MOTS-c may exert as an inhibitor of osteoporosis via AMPK dependent inhibition of osteoclastogenesis.“

Another animal study reported reduced bone erosion and inflammation in a model of osteolysis induced by ultra-high molecular weight polyethylene particles.^[15] MOTS-c appeared to increase the osteoprotegerin ratio to receptor activator of nuclear factor kappa-B ligand in osteocytes, inhibiting osteoclastogenesis.

Some laboratory experiments suggest that MOTS-c may promote bone fracture healing by inducing bone marrow stem cell (BMSCs) differentiation into osteoblasts.^[16] This may be achieved by increasing the relative levels of bone markers (ALP, Bglap, and Runx2) and activating the TGF-β pathway by the FOXF1 protein to ultimately stimulate the mineralization ability in BMSCs.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

---

1. Ming W, Lu G, Xin S, Huanyu L, Yinghao J, Xiaoying L, Chengming X, Banjun R, Li W, Zifan L. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. Biochem Biophys Res Commun. 2016 Aug 5;476(4):412-419. doi: 10.1016/j.bbrc.2016.05.135. Epub 2016 May 26. PMID: 27237975.
2. 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.
3. 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.
4. Lu H, Tang S, Xue C, Liu Y, Wang J, Zhang W, Luo W, Chen J. Mitochondrial-Derived Peptide MOTS-c Increases Adipose Thermogenic Activation to Promote Cold Adaptation. Int J Mol Sci. 2019 May 17;20(10):2456. doi: 10.3390/ijms20102456. PMID: 31109005; PMCID: PMC6567243.
5. Yin Y, Pan Y, He J, Zhong H, Wu Y, Ji C, Liu L, Cui X. The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus. Pharmacol Res. 2022 Jan;175:105987. doi: 10.1016/j.phrs.2021.105987. Epub 2021 Nov 17. PMID: 34798268.
6. Kumagai H, Coelho AR, Wan J, Mehta HH, Yen K, Huang A, Zempo H, Fuku N, Maeda S, Oliveira PJ, Cohen P, Kim SJ. MOTS-c reduces myostatin and muscle atrophy signaling. Am J Physiol Endocrinol Metab. 2021 Apr 1;320(4):E680-E690. doi: 10.1152/ajpendo.00275.2020. Epub 2021 Feb 8. PMID: 33554779; PMCID: PMC8238132.
7. Ran N, Lin C, Leng L, Han G, Geng M, Wu Y, Bittner S, Moulton HM, Yin H. MOTS-c promotes phosphorodiamidate morpholino oligomer uptake and efficacy in dystrophic mice. EMBO Mol Med. 2021 Feb 5;13(2):e12993. doi: 10.15252/emmm.202012993. Epub 2020 Dec 18. PMID: 33337582; PMCID: PMC7863382.
8. Zhong P, Peng J, Hu Y, Zhang J, Shen C. Mitochondrial derived peptide MOTS-c prevents the development of heart failure under pressure overload conditions in mice. J Cell Mol Med. 2022 Nov;26(21):5369-5378. doi: 10.1111/jcmm.17551. Epub 2022 Sep 25. PMID: 36156853; PMCID: PMC9639045.
9. Wang M, Wang G, Pang X, Ma J, Yuan J, Pan Y, Fu Y, Laher I, Li S. MOTS-c repairs myocardial damage by inhibiting the CCN1/ERK1/2/EGR1 pathway in diabetic rats. Front Nutr. 2023 Jan 4;9:1060684. doi: 10.3389/fnut.2022.1060684. PMID: 36687680; PMCID: PMC9846618.
10. Shen C, Wang J, Feng M, Peng J, Du X, Chu H, Chen X. The Mitochondrial-Derived Peptide MOTS-c Attenuates Oxidative Stress Injury and the Inflammatory Response of H9c2 Cells Through the Nrf2/ARE and NF-κB Pathways. Cardiovasc Eng Technol. 2022 Oct;13(5):651-661. doi: 10.1007/s13239-021-00589-w. Epub 2021 Dec 2. PMID: 34859377.
11. Wei M, Gan L, Liu Z, Liu L, Chang JR, Yin DC, Cao HL, Su XL, Smith WW. Mitochondrial-Derived Peptide MOTS-c Attenuates Vascular Calcification and Secondary Myocardial Remodeling via Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway. Cardiorenal Med. 2020;10(1):42-50. doi: 10.1159/000503224. Epub 2019 Nov 6. PMID: 31694019.
12. Yuan J, Wang M, Pan Y, Liang M, Fu Y, Duan Y, Tang M, Laher I, Li S. The mitochondrial signaling peptide MOTS-c improves myocardial performance during exercise training in rats. Sci Rep. 2021 Oct 11;11(1):20077. doi: 10.1038/s41598-021-99568-3. PMID: 34635713; PMCID: PMC8505603.
13. Yuan J, Xu B, Ma J, Pang X, Fu Y, Liang M, Wang M, Pan Y, Duan Y, Tang M, Zhu B, Laher I, Li S. MOTS-c and aerobic exercise induce cardiac physiological adaptation via NRG1/ErbB4/CEBPβ modification in rats. Life Sci. 2023 Feb 15;315:121330. doi: 10.1016/j.lfs.2022.121330. Epub 2022 Dec 28. PMID: 36584915.
14. Ming W, Lu G, Xin S, Huanyu L, Yinghao J, Xiaoying L, Chengming X, Banjun R, Li W, Zifan L. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. Biochem Biophys Res Commun. 2016 Aug 5;476(4):412-419. doi: 10.1016/j.bbrc.2016.05.135. Epub 2016 May 26. PMID: 27237975.
15. Yan Z, Zhu S, Wang H, Wang L, Du T, Ye Z, Zhai D, Zhu Z, Tian X, Lu Z, Cao X. MOTS-c inhibits osteolysis in the Mouse Calvaria by affecting osteocyte-osteoclast crosstalk and inhibiting inflammation. Pharmacol Res. 2019 Sep;147:104381. doi: 10.1016/j.phrs.2019.104381. Epub 2019 Jul 29. PMID: 31369811.
16. Weng FB, Zhu LF, Zhou JX, Shan Y, Tian ZG, Yang LW. MOTS-c accelerates bone fracture healing by stimulating osteogenesis of bone marrow mesenchymal stem cells via positively regulating FOXF1 to activate the TGF-β pathway. Eur Rev Med Pharmacol Sci. 2021 Mar;25(6):2459. doi: 10.26355/eurrev_202103_25396. PMID: 33829422.

Ipamorelin, also known as NNC 26-0161, is a pentapeptide with the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2. Researchers suggest it may induce a peak in growth hormone (GH) synthesis by the pituitary gland via activating the growth hormone secretagogue receptors (GHS-Rs). In this respect, Ipamorelin is classified as a growth hormone secretagogue (GHS). It appears mimic the hunger hormone Ghrelin, which is considered a natural activator of the GHS-Rs.

Ipamorelin peptide appears to differentiate itself from other GHSs as a potentially more selective option that elevates GH levels without increasing other pituitary hormones, such as prolactin. Studies are still underway with this peptide within the context of postoperative ileus and speeding up the recovery of gastrointestinal function following damage.

 

Research

 

Ipamorelin and Growth Hormonse Synthesis

Studies suggest that Ipamorelin may be a highly selective growth hormone secretagogue, which may be capable of increasing GH levels in animals by activating the GHS-R receptors.^[1,2]

Research studies report that the effect may occur relatively quickly – as soon as 40 minutes after exposure, there appeared to be a peak in GH levels. Increasing GH levels may potentially have numerous potential impacts, such as preserving muscle and lean body mass, increasing energy levels, improving bone mineral density, and more. ^[3]

 

Ipamorelin and Gastrointestinal Functions

Ipamorelin has been studied for its potential to alleviate delayed gastric emptying and post-surgical ileus in animals. In rodents, the peptide may significantly accelerate the rate of gastric emptying through stimulating gastric contractility.^[4] The route via which the peptide may act appears to be by activating a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons. The researchers reported that “Ipamorelin (0.014 µmol/kg intravenous) resulted in a significant acceleration (P < 0.05 vs vehicle-treated rat) of gastric emptying with 52% ± 11% of the meal remaining in the stomach compared to nonsurgical control animals with 44% ± 6%.”

 

Ipamorelin and Appetite, Weight

Existing research suggests that Ipamorelin may increase appetite, reduce weight loss in the context of research studies in wasting disorders. This hypothesis is based on animal study findings. According to the researchers, these hypotheses are due to the apparent appetite-increasing characteristics of Ipamorelin.^[5] The peptide appears to activate the receptors of the hunger hormone, which in turn may result in an increased food intake.

On the other hand, any growth hormone-increasing potential of Ipamorelin may also help reduce weight loss, especially protein loss. Studies posit that Ipamorelin may reduce muscle wasting in cortisol-exposed animals and help maintain a positive nitrogen balance.^[6] The researchers conclude that “Accelerated nitrogen wasting in the liver and other organs caused by prednisolone [exposure] was counteracted by [influence] with either GH or its secretagogue Ipamorelin.”

Another trial observes that Ipamorelin appears to negate the GH-inhibiting action of glucocorticoids in tested animals.^[7] Animal studies suggest that Ipamorelin may also stimulate insulin secretion, another anabolic hormone that can help reduce muscle loss in wasting disorders.^[8]

 

Ipamorelin and Bone

Growth hormones are considered a factor in maintaining optimal bone mineral density. Animal studies suggest that thanks to Ipamorelin’s alleged action on growth hormone synthesis and body weight, it may help maintain or even increase bone mass. One study on thirteen-week-old female Sprague-Dawley rats suggested that Ipamorelin exposure appeared to significantly increase bone mineral content after 12 weeks.^[9] The increase was measured via a DEXA (dual-energy X-ray absorptiometry) scan and was significantly higher than the placebo group.

Another animal trial on rats treated with glucocorticoids reported that Ipamorelin has the potential to completely negate bone loss induced by glucocorticoids.^[10] The scientists report that the periosteal bone formation rate increased four-fold in animals exposed to glucocorticoids and Ipamorelin in combination, compared with the group that received glucocorticoids alone.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

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1. Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61. doi: 10.1530/eje.0.1390552. PMID: 9849822.
2. Gobburu JV, Agersø H, Jusko WJ, Ynddal L. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res. 1999 Sep;16(9):1412-6. doi: 10.1023/a:1018955126402. PMID: 10496658.
3. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis. 2014 Dec;29(12):1527-34. doi: 10.1007/s00384-014-2030-8. Epub 2014 Oct 21. PMID: 25331030.
4. Greenwood-Van Meerveld B, Tyler K, Mohammadi E, Pietra C. Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. J Exp Pharmacol. 2012 Oct 19;4:149-55. doi: 10.2147/JEP.S35396. PMID: 27186127; PMCID: PMC4863553.
5. Lall S, Tung LY, Ohlsson C, Jansson JO, Dickson SL. Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues. Biochem Biophys Res Commun. 2001 Jan 12;280(1):132-8. doi: 10.1006/bbrc.2000.4065. PMID: 11162489.
6. Aagaard NK, Grøfte T, Greisen J, Malmlöf K, Johansen PB, Grønbaek H, Ørskov H, Tygstrup N, Vilstrup H. Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats. Growth Horm IGF Res. 2009 Oct;19(5):426-31. doi: 10.1016/j.ghir.2009.01.001. Epub 2009 Feb 23. PMID: 19231263.
7. Malmlöf K, Johansen PB, Haahr PM, Wilken M, Oxlund H. Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats. Growth Horm IGF Res. 1999 Dec;9(6):445-50. doi: 10.1054/ghir.1999.0128. PMID: 10629165.
8. Adeghate E, Ponery AS. Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats. Neuro Endocrinol Lett. 2004 Dec;25(6):403-6. PMID: 15665799.
9. Svensson J, Lall S, Dickson SL, Bengtsson BA, Rømer J, Ahnfelt-Rønne I, Ohlsson C, Jansson JO. The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. J Endocrinol. 2000 Jun;165(3):569-77. doi: 10.1677/joe.0.1650569. PMID: 10828840.
10. Andersen NB, Malmlöf K, Johansen PB, Andreassen TT, Ørtoft G, Oxlund H. The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth Horm IGF Res. 2001 Oct;11(5):266-72. doi: 10.1054/ghir.2001.0239. PMID: 11735244

BPC-157 is a pentadecapeptide made of 15 amino acids and bears the sequence Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, and a molecular formula of C₆₂H₉₈N₁₆O₂₂. This is a fully synthetic peptide with a sequence not known to occur in nature. However, it is often termed a “gut peptide,” as it is suggested to have similar structure and properties to other gastroprotective peptides found in gastric juice.

According to the patent, the peptide’s production is fully synthetic and derived from various organic and inorganic bases. BPC stands for ‘Body Protection Compound.’ It appears to be relatively stable in stomach acid compared to other peptides.

Animal studies indicate the peptide’s potential to modulate the healing of various tissues, including tendons, joints, nerves, the intestinal tract, and skin. BPC-157 likely works via various pathways, including anti-inflammatory action, modulated nitric oxide synthesis, increased growth factor synthesis, and activation of cells involved in tissue repair.

 

Research

 

BPC-157 Peptide and the Digestive System

BPC-157 peptide is under investigation for its potential to protect against and treat ulcers in the gastrointestinal system. Animal studies suggest that the peptide has significant protective effects against compounds which are known to cause stomach ulcers.^[1][2] Sikiric et al. report that “superior protection against different gastrointestinal and liver lesions and anti-inflammatory and analgesic activities were noted for pentadecapeptide BPC.” Researchers also suggest that this protective potential is likely related to the action of BPC-157 peptide on the alpha-adrenergic (e.g., catecholamine release) and dopaminergic (central) systems. Blocking the alpha-adrenergic or dopamine receptors may reduce the effectiveness of BPC-157 against ulcerations.

The peptide may also work by stimulating the synthesis of growth factors in the intestinal cells that cover the digestive system. Another laboratory study reports that BPC-157 peptide has also been suggested to stimulate the mRNA of the growth factor EGR-1.^[3] As a result, experiments in rats report that BPC-157 peptide speeds up the healing of surgical injuries in the gastrointestinal system, specifically esophagogastric anastomosis healing.^[4] Animal models with short-bowel syndrome also report that the peptide may help prevent weight loss and increase the ability of the bowels to absorb nutrients.^[5,6] The researchers report constant weight gain and increased villus height, crypt depth, and muscle thickness of the small intestines. Furthermore, the scientists report that “BPC 157 completely ameliorated symptoms in massive intestinal resection.” Because of its interactions with various neurotransmitters, scientists have also investigated its effects on serotonin production. According to preliminary research BPC-157 may exert beneficial action on serotonin synthesis.^[7]

 

BPC-157 Peptide and the Nervous System

Rat studies report that BPC-175 may significantly increase serotonin synthesis in several brain regions, including the “substantia nigra reticulata and medial anterior olfactory nucleus,” taking only 40 minutes for BPC-157 to exert these effects.^[8]  One study in rats reported that BPC-157 peptide exhibited possible antidepressant characteristics when the animals were exposed to acute or chronic stress.^[9]

BPC-157 peptide may also help ameliorate damage to the brain through various chemicals. According to one experiment which used cuprizone to induce brain damage and nerve demyelination like those observed in multiple sclerosis (MS), BPC-157 had potential protective action.^[10] BPC-157 peptide appeared to have reduced the number of damaged cells in numerous brain regions, including the hippocampus. Another study that used a toxin to induce damage, like what is seen in Parkinson’s Disease in rodents, reports that BPC-157 may exerts protective action.^[11]

 

BPC-157 Peptide and Skin, Bones, and Joints

BPC-157 peptide may have action that extend beyond the gastrointestinal and nervous systems, such as stimulating the repair of the skin tissues, bones, joints, tendons, and other tissues. These possible actions could be due to the potential of BPC-157 peptide to stimulate the formation of new blood vessels. By stimulating angiogenesis, BPC-157 may increase the supply of tissues with nutrients and growth factors.

According to one study in rats with injured limbs, the scientists noted an increase in VEGFR2 expression, which was much more significant compared to controls.^[12] Hsieh et al. also noted that “BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia.”

In tendon and joint injuries, BPC-157 peptide may also speed up the recovery of connective tissues by upregulating fibroblast function. Experiments note that BPC-157 may allow tendon fibroblasts to grow and spread faster.^[13] The researchers note that the effect was present only when the fibroblasts were replanted. Another experiment also reported increased wound healing potential in rats after injuries induced via surgical cuts. The researchers hypothesized that BPC-157 peptide might significantly increase the rate of injury healing when compared to the control.^[14]

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

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1. Luetic K, Sucic M, Vlainic J, Halle ZB, Strinic D, Vidovic T, Luetic F, Marusic M, Gulic S, Pavelic TT, Kokot A, Seiwerth RS, Drmic D, Batelja L, Seiwerth S, Sikiric P. Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157. Inflammopharmacology. 2017 Apr;25(2):255-264. doi: 10.1007/s10787-017-0330-7. Epub 2017 Mar 2. PMID: 28255738.
2. Sikirić P, Mazul B, Seiwerth S, Grabarević Z, Rucman R, Petek M, Jagić V, Turković B, Rotkvić I, Mise S, Zoricić I, Jurina L, Konjevoda P, Hanzevacki M, Gjurasin M, Separović J, Ljubanović D, Artuković B, Bratulić M, Tisljar M, Miklić P, Sumajstorcić J. Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress. Dig Dis Sci. 1997 Mar;42(3):661-71. doi: 10.1023/a:1018880000644. PMID: 9073154.
3. Tkalcević VI, Cuzić S, Brajsa K, Mildner B, Bokulić A, Situm K, Perović D, Glojnarić I, Parnham MJ. Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression. Eur J Pharmacol. 2007 Sep 10;570(1-3):212-21. doi: 10.1016/j.ejphar.2007.05.072. Epub 2007 Jun 16. PMID: 17628536.
4. Djakovic Z, Djakovic I, Cesarec V, Madzarac G, Becejac T, Zukanovic G, Drmic D, Batelja L, Zenko Sever A, Kolenc D, Pajtak A, Knez N, Japjec M, Luetic K, Stancic-Rokotov D, Seiwerth S, Sikiric P. Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME. World J Gastroenterol. 2016 Nov 7;22(41):9127-9140. doi: 10.3748/wjg.v22.i41.9127. PMID: 27895400; PMCID: PMC5107594.
5. Sever M, Klicek R, Radic B, Brcic L, Zoricic I, Drmic D, Ivica M, Barisic I, Ilic S, Berkopic L, Blagaic AB, Coric M, Kolenc D, Vrcic H, Anic T, Seiwerth S, Sikiric P. Gastric pentadecapeptide BPC 157 and short bowel syndrome in rats. Dig Dis Sci. 2009 Oct;54(10):2070-83. doi: 10.1007/s10620-008-0598-y. Epub 2008 Dec 18. PMID: 19093208.
6. Lojo N, Rasic Z, Zenko Sever A, Kolenc D, Vukusic D, Drmic D, Zoricic I, Sever M, Seiwerth S, Sikiric P. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats. PLoS One. 2016 Sep 14;11(9):e0162590. doi: 10.1371/journal.pone.0162590. PMID: 27627764; PMCID: PMC5023193.
7. Sikiric P, Seiwerth S, Rucman R, Kolenc D, Vuletic LB, Drmic D, Grgic T, Strbe S, Zukanovic G, Crvenkovic D, Madzarac G, Rukavina I, Sucic M, Baric M, Starcevic N, Krstonijevic Z, Bencic ML, Filipcic I, Rokotov DS, Vlainic J. Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications. Curr Neuropharmacol. 2016;14(8):857-865. doi: 10.2174/1570159×13666160502153022. PMID: 27138887; PMCID: PMC5333585.
8. Tohyama Y, Sikirić P, Diksic M. Effects of pentadecapeptide BPC157 on regional serotonin synthesis in the rat brain: alpha-methyl-L-tryptophan autoradiographic measurements. Life Sci. 2004 Dec 3;76(3):345-57. doi: 10.1016/j.lfs.2004.08.010. PMID: 15531385.
9. Sikiric P, Separovic J, Buljat G, Anic T, Stancic-Rokotov D, Mikus D, Marovic A, Prkacin I, Duplancic B, Zoricic I, Aralica G, Lovric-Bencic M, Ziger T, Perovic D, Rotkvic I, Mise S, Hanzevacki M, Hahn V, Seiwerth S, Turkovic B, Grabarevic Z, Petek M, Rucman R. The antidepressant effect of an antiulcer pentadecapeptide BPC 157 in Porsolt’s test and chronic unpredictable stress in rats. A comparison with antidepressants. J Physiol Paris. 2000 Mar-Apr;94(2):99-104. doi: 10.1016/s0928-4257(00)00148-0. PMID: 10791689.
10. Klicek R, Kolenc D, Suran J, Drmic D, Brcic L, Aralica G, Sever M, Holjevac J, Radic B, Turudic T, Kokot A, Patrlj L, Rucman R, Seiwerth S, Sikiric P. Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability. J Physiol Pharmacol. 2013 Oct;64(5):597-612. PMID: 24304574.
11. Sikiric P, Marovic A, Matoz W, Anic T, Buljat G, Mikus D, Stancic-Rokotov D, Separovic J, Seiwerth S, Grabarevic Z, Rucman R, Petek M, Ziger T, Sebecic B, Zoricic I, Turkovic B, Aralica G, Perovic D, Duplancic B, Lovric-Bencic M, Rotkvic I, Mise S, Jagic V, Hahn V. A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson’s disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine. J Physiol Paris. 1999 Dec;93(6):505-12. doi: 10.1016/s0928-4257(99)00119-9. PMID: 10672997.
12. Hsieh MJ, Liu HT, Wang CN, Huang HY, Lin Y, Ko YS, Wang JS, Chang VH, Pang JS. Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. J Mol Med (Berl). 2017 Mar;95(3):323-333. doi: 10.1007/s00109-016-1488-y. Epub 2016 Nov 15. PMID: 27847966.
13. Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J Appl Physiol (1985). 2011 Mar;110(3):774-80. doi: 10.1152/japplphysiol.00945.2010. Epub 2010 Oct 28. PMID: 21030672.
14. Staresinic M, Sebecic B, Patrlj L, Jadrijevic S, Suknaic S, Perovic D, Aralica G, Zarkovic N, Borovic S, Srdjak M, Hajdarevic K, Kopljar M, Batelja L, Boban-Blagaic A, Turcic I, Anic T, Seiwerth S, Sikiric P. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. J Orthop Res. 2003 Nov;21(6):976-83. doi: 10.1016/S0736-0266(03)00110-4. PMID: 14554208.