GHRP-2 and Ipamorelin are research peptides that are commonly referred to as growth hormone secretagogues (GHSs). This is because they both have the potential to interact with a specific subset of receptors in pituitary gland cells, which are called growth hormone secretagogue receptors. As evident from the name of the receptors, their activation may trigger the release of growth hormone from the anterior pituitary cells. These receptors are different from the GHRH receptors, which are normally activated by the GHRH hormone and are considered to be the main endogenous receptors that play a role in endogenous growth hormone production. Here are more details about the structure and peculiarities of each peptide:

• GHRP-2 refers to “growth hormone-releasing peptide-2“, and it is a hexapeptide.^[1] This compound is categorized within the broader group of GHRPs, which is said to be synthesized from endogenously occurring molecules referred to as met-enkephalins. However, GHRPs do not appear to interact with the receptors for met-enkephalin; instead, they interact with the GHS receptors. GHRP-2 appears to be a non-selective agonist of these receptors. Therefore, it potentially affects growth hormone production in the pituitary gland and possibly modulates the activity of other pituitary-derived hormones.
• Ipamorelin, sometimes identified by the designation NNC 26-0161, is described as a pentapeptide and may be represented by the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2.^[2] Classified as a GHRP and GHS, Ipamorelin is commonly thought to be more selective for stimulating growth hormone secretion, potentially causing less influence on non-growth hormone pituitary hormones compared to other members of this peptide family. Researchers have commented that “ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation.”

 

Mechanisms of Action

Ipamorelin and GHRP-2, though structurally distinct, may nonetheless engage with similar underlying biological processes. Both peptides may potentially act on a specific subset of pituitary receptors, often referred to as ghrelin receptors or growth hormone secretagogue receptor 1a (GHS-R1a), which might generally respond to the hormone ghrelin. Upon their proposed interaction with GHS-R1a, these compounds may induce subtle receptor conformational changes that might trigger a sequence of intricate intracellular signaling pathways.^[3] Within these pathways, phospholipase C (PLC) may serve as a key enzyme, as some researchers suspect it might promote the formation of second messengers, such as inositol triphosphate (IP3) and diacylglycerol (DAG).

If these messengers are indeed produced, IP3 might facilitate the controlled release of calcium ions (Ca2+) from internal stores, and DAG may potentially contribute to the activation of protein kinase C (PKC). This enzyme family might influence various cellular functions. The combined action of increased intracellular calcium and possible PKC activation may, in turn, modulate the transcription of genes believed to be involved in growth hormone production and secretion.

 

Scientific and Research Studies

 

Ipamorelin & GHRP-2 Blend and Growth Hormone Signaling

While conclusive data remain scarce, early investigations into GHRP-2 and Ipamorelin may provide some preliminary insights into their potential influence on pituitary cells and their ability for growth hormone synthesis. Growth hormone is considered to be a hormone that has a combination of anabolic and catabolic properties. These properties are of significant research interest to researchers in different fields. Notably, its anabolic properties are considered to be mediated by another mediator called insulin-like growth factor-1 (IGF-1). Consequently, by upregulating growth hormone synthesis, GHRP-2 and Ipamorelin may also upregulate IGF-1. Here are some of the most notable early investigations into GHRP-2 and Ipamorelin potential:

• Studies into GHRP-2 suggest that it might upregulate growth hormone release from anterior pituitary cells by as much as 181 times above the levels measured before exposure to the peptide.^[4] Preliminary data also indicates that mean IGF-1 concentrations might rise by about 80% following exposure to GHRP-2. Another study comparing GHRP-2 to placebo suggested an almost 6-fold higher peak increase in growth hormone synthesis from pituitary cells.^[5]
• In studies examining Ipamorelin, preliminary data imply that growth hormone synthesis may spike substantially, potentially reaching nearly 27 nanograms per milliliter (ng/ml), which is over 60 times greater than the typical 0.4 ng/ml values observed in placebo experiments.^[6]

 

Ipamorelin & GHRP-2 Blend in Muscle Cell Hypertrophy

GHRP-2 and Ipamorelin have both been examined for their possible roles in promoting muscle cell hypertrophy—an increase in the size of muscle cells. This hypertrophy is thought to be associated with increases in growth hormone and IGF-1, both of which can potentially induce anabolic processes. For example, some investigators have hypothesized that GHRP-2, under certain experimental conditions, might influence muscular tissue protein metabolism in a manner that might favor protein synthesis over degradation. In one study conducted on yaks (Bos grunniens), it was proposed that GHRP-2 may have supported muscular tissue protein building through pathways that potentially support protein synthesis rates.^[7] Notably, the researchers commented that “GHRP-2 … muscle protein deposition mainly by up-regulating the protein synthesis pathways”. However, this possibility was considered within the context of experimental models facing limited nutrient availability, challenging environmental conditions, and disease-related stressors, where atrophy may prevail.

The researchers speculated that GHRP-2 might have also contributed to minimizing muscular tissue atrophy in these challenging settings. Similarly, Ipamorelin has been speculated to slow the loss of muscle cells in models of muscular tissue wasting, possibly by indirectly affecting IGF-1 levels in muscular tissues. Some preliminary data suggests that Ipamorelin might mitigate muscular tissue wasting in scenarios involving high corticosteroid levels, as corticosteroids can often promote muscular tissue breakdown.^[8] The underlying processes may be linked to IGF-1-mediated downregulation of enzymes referred to as E3 ubiquitin ligases—including atrogin-1 and MuRF1 (muscle ring finger protein-1)—both of which are commonly associated with protein breakdown in muscle cells. Both peptides may upregulate anabolic signals like IGF-1 that reduce the activity of atrogin-1 and MuRF1, thereby possibly diminishing the pace of protein degradation within muscle cells.^[9]

 

Ipamorelin & GHRP-2 Blend in Bone Tissues

Ipamorelin has been investigated for its potential influences on bone tissues, including possible actions on the formation of new bone and the overall amount of mineral content within skeletal structures. Observations in certain experimental models have hinted that Ipamorelin may contribute to a relative rise in bone mineral content (BMC), which refers to the total mineral content in bone.^[10,11] According to the observations, Ipamorelin exposure was associated with potential increases in bone size, weight, and BMC, although the underlying mechanisms were not fully understood.

The interpretation of such findings is tentative, as the volumetric bone mineral density (BMD) did not consistently increase in parallel. Instead, it appeared that any observed rise in BMC might have stemmed from changes in bone geometry rather than a uniform elevation in mineral density. Although not firmly established, Ipamorelin’s role in possibly stimulating GH and IGF-1 signaling pathways may be one explanation for these skeletal changes. Adding GHRP-2 may theoretically intensify these processes, but at present, data remains limited.

 

Ipamorelin & GHRP-2 Blend and Hunger Hormone Signaling

Apart from interacting with the GHS-R1a in the pituitary gland cells, GHRPs like GHRP-2 and Ipamorelin have also been suggested to interact with the same receptors in other cells, similarly to the interaction of the endogenous hunger hormone ghrelin. Therefore, these peptides are thought to mediate a similar appetite-promoting signaling as ghrelin. In fact, activating these receptors in certain neurons can influence the production of neuropeptides involved in appetite regulation, such as neuropeptide Y (NPY) and agouti-related peptide (AgRP). These neuropeptides are commonly associated with increasing appetite. Activating the GHS-R1a may also mediate the suppression of alpha-melanocyte-stimulating hormone (α-MSH), which usually reduces appetite.

Experiments with GHRP-2 and Ipamorelin also seem to suggest that. For example, there was a study in laboratory models where Ipamorelin-exposed subjects appeared to experience measurable increases in food intake and overall mass, possibly including a rise in adipose (fat) tissue, on the order of roughly 15%.^[12] According to another group of researchers, GHRP-2 exposure was also suggested to increase food consumption by approximately 36% compared to controls, potentially translating to higher energy intake per unit of mass. The energy consumption was reposted to increase to 136.0±13.0 kilojoules per kilogram, as opposed to 101.3±10.5 kilojoules per kilogram in controls.^[13] Although the biological mechanisms remain incompletely characterized, these findings raise the possibility that Ipamorelin and GHRP-2 may modulate energy balance and physical composition through a combination of influencing anabolic signaling and hunger hormone signaling.

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. Berlanga-Acosta J, Abreu-Cruz A, Herrera DGB, Mendoza-Marí Y, Rodríguez-Ulloa A, García-Ojalvo A, Falcón-Cama V, Hernández-Bernal F, Beichen Q, Guillén-Nieto G. Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects. Clin Med Insights Cardiol. 2017 Mar 2;11:1179546817694558. doi: 10.1177/1179546817694558. PMID: 28469491; PMCID: PMC5392015.
2. 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.
3. Jiménez-Reina L, Cañete R, de la Torre MJ, Bernal G. Influence of chronic treatment with the growth hormone secretagogue Ipamorelin, in young female rats: somatotroph response in vitro. Histol Histopathol. 2002;17(3):707-14. doi: 10.14670/HH-17.707. PMID: 12168778.
4. Veldhuis, J. D., Keenan, D. M., Bailey, J. N., Adeniji, A. M., Miles, J. M., & Bowers, C. Y. (2009). Novel relationships of age, visceral adiposity, insulin-like growth factor (IGF)-I and IGF binding protein concentrations to growth hormone (GH) releasing-hormone and GH releasing-peptide efficacies in men during experimental hypogonadal clamp. The Journal of clinical endocrinology and metabolism, 94(6), 2137–2143. https://doi.org/10.1210/jc.2009-0136
5. Bowers, C. Y., Granda, R., Mohan, S., Kuipers, J., Baylink, D., & Veldhuis, J. D. (2004). Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women. The Journal of clinical endocrinology and metabolism, 89(5), 2290–2300. https://doi.org/10.1210/jc.2003-031799
6. Gobburu, J. V., Agersø, H., Jusko, W. J., & Ynddal, L. (1999). Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharmaceutical research, 16(9), 1412–1416. https://doi.org/10.1023/a:1018955126402
7. Hu R, Wang Z, Peng Q, Zou H, Wang H, Yu X, Jing X, Wang Y, Cao B, Bao S, Zhang W, Zhao S, Ji H, Kong X, Niu Q. Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation. PLoS One. 2016 Feb 19;11(2):e0149461. doi: 10.1371/journal.pone.0149461. PMID: 26894743; PMCID: PMC4760683.
8. Andersen, N. B., Malmlöf, K., Johansen, P. B., Andreassen, T. T., Ørtoft, G., & Oxlund, H. (2001). The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation in adult rats. Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society, 11(5), 266–272. https://doi.org/10.1054/ghir.2001.0239
9. Sacheck, J. M., Ohtsuka, A., McLary, S. C., & Goldberg, A. L. (2004). IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. American journal of physiology. Endocrinology and metabolism, 287(4), E591–E601. https://doi.org/10.1152/ajpendo.00073.2004
10. Johansen PB, Nowak J, Skjaerbaek C, Flyvbjerg A, Andreassen TT, Wilken M, Orskov H. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res. 1999 Apr;9(2):106-13. doi: 10.1054/ghir.1999.9998. PMID: 10373343.
11. 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.
12. 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
13. Laferrère, Blandine, et al. “Growth hormone-releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.” The Journal of Clinical Endocrinology and Metabolism vol. 90,2 (2005): 611-4.

CJC-1295 & Ipamorelin & GHRP-2 are research peptides that are believed to interact with different receptors on pituitary gland cells. These cells are thought to produce a wide variety of hormonal substances that consequently regulate other endocrine cells and tissues. CJC-1295 & Ipamorelin & GHRP-2, in particular, are thought to stimulate the potential of pituitary cells for synthesizing growth hormone. Here are details for each of these peptides:

• CJC-1295 belongs to a class of molecules referred to as growth hormone-releasing hormone (GHRH) agonists.^[1] It is made of the first 29 amino acids of the native GHRH hormone, representing the shortest functional sequence of GHRH. Further, CJC-1295 appears to have several modifications, including the replacement of four of the original amino acids in the GHRH 1-29 sequence, as well as the attachment of a rug affinity complex (DAC) component that may bind to plasma proteins. More specifically, the DAC component in CJC-1295 refers to the attachment of N-epsilon-3-maleimidopropionamide derivative at the C terminus. These modifications are posited to support the stability of the molecule and prolong its half-life.
• Ipamorelin, also referred to as NNC 26-0161, is a pentapeptide with the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2.^[2] This molecule belongs to the family of growth hormone-releasing peptides (GHRPs), which were initially derived from the structure of endogenously occurring pentapeptides called metenkephalins. Ipamorelin appears to be highly selective towards triggering the release of growth hormone from the pituitary gland cells.
• GHRP-2 (growth hormone-releasing peptide-2) appears to belong to the GHRP class as well.^[3] It is a hexapeptide developed from the structure of met-enkephalins. Yet, GHRP-2 appears to be less selective in its actions compared to Ipamorelin.

 

Mechanisms of Action

While it is believed that all three peptides may interact with the pituitary gland cells to stimulate growth hormone release, they may do so via different mechanisms:

• Interaction with the GHRH receptors: CJC-1295 appears to function primarily via the GHRH receptors found on pituitary gland cells. These receptors normally respond to the GHRH hormone, but CJC-1295 appears to induce similar activation. When CJC-1295 binds to this receptor on pituitary cells, it may activate intracellular proteins referred to as G-proteins. This might stimulate the production of second messengers such as cyclic adenosine monophosphate (cAMP) and inositol trisphosphate (IP₃). These small molecules are believed to serve as internal signals, potentially propagating the message deeper into the cell by relaying and amplifying the signal received at the cell surface. The increase in second messengers like cAMP is believed to activate enzymes called protein kinases. Once phosphorylated, these transcription factors may enter the cell nucleus and potentially modulate the transcription of genes involved in the synthesis and secretion of growth hormone.
• Interactions with ghrelin receptors: Ipamorelin and GHRP-2 appear to interact with a different subtype of pituitary receptors, called “ghrelin receptors” or also “growth hormone secretagogue receptor 1a” (GHS-R1a). These receptors normally respond to the hunger hormone ghrelin. GHRPs like GHRP-2 and Ipamorelin are also thought to activate these receptors and are consequently also referred to as growth hormone secretagogues. Once these peptides bind to the GHS-R1a, they appear to induce conformational changes that lead to the production of transcription factors. The latter may enter the pituitary cell nucleus and modulate the transcription of genes involved in the production and release of growth hormone.

 

Scientific and Research Studies

 

CJC-1295 & Ipamorelin & GHRP-2 Blend and Growth Hormone Signaling

All three of these peptides are believed to interact with the pituitary gland cells, which may potentially stimulate the release of growth hormone. The production of growth hormone may interact with receptors on the liver, muscle cells, and other cells, potentially initiating a series of intracellular signaling events such as activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway.^[4]

Following activation, STAT proteins may translocate to the nucleus and bind to specific DNA sequences referred to as response elements, which might facilitate the transcription of genes involved in the synthesis of insulin-like growth factor-1 (IGF-1). This is the main anabolic mediator of growth hormone, and CJC-1295 & Ipamorelin & GHRP-2 are expected to upregulate the synthesis of both the growth hormone and IGF-1 in experimental models. Unfortunately, no studies have investigated their potential as a blend, but several trials have experimented with each of the peptides individually and report the following observations:

• Experimental studies suggest that CJC-1295 may increase the synthesis of growth hormone by approximately 2- to 10-fold compared to placebo models.^[5] Peak levels of growth hormone are reported to occur around two hours after introducing CJC-1295, and this elevated activity might persist for up to six days. Consequently, CJC-1295 may potentially contribute to average levels of IGF-1 increasing by about 1.5- to 3-fold throughout approximately 9 to 11 days. Additionally, repeated exposure to CJC-1295 appears to maintain elevated IGF-1 levels above baseline for up to 28 days.
• In studies involving Ipamorelin, it has been observed that growth hormone levels may increase significantly, potentially reaching up to 80 milli-International Units per liter (mIU/l), which corresponds to approximately 26.6 nanograms per milliliter (ng/ml).^[6] Compared to the growth hormone levels around 1.31 mIU/l (0.4 ng/ml) with placebo, this represents what seems to be a substantial elevation in growth hormone concentration.
• Research on GHRP-2 suggests that it might stimulate growth hormone production from anterior pituitary cells up to 181 times the baseline levels.^[7] Furthermore, some studies report that IGF-1 levels may increase from an average of 100 micrograms per liter (mcg/l) at baseline to approximately 180 mcg/l following GHRP-2 exposition. Another group of researchers found that GHRP-2 appears to stimulate the pulsatile, rhythmic, and entropic secretion of growth hormone by more than threefold compared to GHRH.^[8]

 

CJC-1295 & Ipamorelin & GHRP-2 Blend and Hunger Hormone Signaling

While CJC-1295 appears to interact with the GHRH receptors, which do not affect hunger hormone signaling, Ipamorelin & GHRP-2 interact with the GHSR1a receptors, which are also referred to as the ghrelin receptors as the hunger hormone ghrelin activates them. Activation of GHSR1a receptors may promote the production of hunger hormone-stimulating neuropeptides, such as neuropeptide Y (NPY) and agouti-related peptide (AgRP), while potentially suppressing the release of alpha-melanocyte-stimulating hormone (α-MSH), an appetite-suppressing hormone.

Some studies have suggested that laboratory models exposed to Ipamorelin may experience a notable increase in hunger hormone signaling. This may lead to an increase in the size and weight of research models by approximately 15%, possibly due to a rise in adipose tissue relative to total mass.^[9] Additionally, research indicates that models exposed to GHRP-2 may consume approximately 36% more food than control models, suggesting an increase in food intake relative to mass. Specifically, the energy intake per kilogram of mass in the GHRP-2 group was observed to be 136.0±13.0 kilojoules per kilogram, compared to 101.3±10.5 kilojoules per kilogram in the control group.^[10]

 

CJC-1295 & Ipamorelin & GHRP-2 Blend in Bone Tissues

Some research suggests that Ipamorelin might support bone formation and possibly increase overall bone mass.^[11,12] This hypothesis arises from observations implying that Ipamorelin might be associated with an apparent rise in bone mineral content (BMC), which refers to the total amount of minerals in bone tissue. In a particular study involving murine models, scientists examined the potential actions of Ipamorelin on bone mineral content. Researchers have proposed that Ipamorelin may lead to increases in the size, weight, and bone mineral content of experimental animals.

These changes might be measured using dual-energy X-ray absorptiometry (DXA). This non-invasive imaging technique assesses bone density by gauging how bones and soft tissues absorb X-rays. The researchers also commented, “that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged.” Therefore, Ipamorelin appears to mediate this potential by apparently upregulating anabolic growth signals like growth hormone and IGF-1. The addition of CJC-1295 and GHRP-2 may further upregulate this potential, although research is lacking.

 

CJC-1295 & Ipamorelin & GHRP-2 Blend in Muscle Cell Hypertrophy

The potential upregulation of growth hormone and IGF-1 levels by peptides like CJC-1295 & Ipamorelin & GHRP-2 is also expected to lead to increased anabolic signaling with muscular tissue, which is associated with muscle cell hypertrophy (increase in cell size). For example, preliminary research with CJC-1295 analogs suggests that the peptide may induce a notable increase in muscle tissue hypertrophy, leading to an average net gain of lean mass of about 2.77 pounds within 16 weeks.^[13]

Researchers have also posited that “GHRP-2 enhanced muscle protein deposition mainly by

up-regulating the protein synthesis pathways” when conducting research in yaks. The study suggested that GHRP-2 may help to overcome endogenous growth limitations that occur in yaks because of food deprivation, adverse environmental conditions, and disease. Furthermore, GHRP-2 may have indicated potential contributions to reduction in atrophy of muscular tissue through repression of muscle cell-specific enzymes called E3 ubiquitin ligases—such as atrogin-1 and muscle ring finger protein-1 (MuRF1), which are believed to upregulate muscle cell degradation pathways. Specifically, these enzymes are thought to tag proteins for degradation via the ubiquitin-proteasome pathway, a cellular system responsible for breaking down proteins.

It is also theoretically possible that Ipamorelin may also help reduce the loss of muscle cells in catabolic experimental models. This potential might occur by increasing the IGF-1 within muscular tissue. For instance, studies suggest that Ipamorelin may decrease muscular tissue loss in research models exposed to corticosteroids, which are believed to induce the wasting of muscular tissues.^[15] The mechanisms underlying this potential action might involve the suppression of atrogin-1 and MuRF1, mediated by IGF-1. By possibly downregulating these ligases, IGF-1 may reduce muscle cell protein degradation and assist in preserving muscle cells.^[16]

 

CJC-1295 & Ipamorelin & GHRP-2 Blend Synergy

Given that CJC-1295 may operate through a different biological pathway than Ipamorelin and GHRP-2, which are synthetic growth hormone secretagogues, some researchers hypothesize that combining these compounds may produce a synergistic action on somatotroph cells and induce an even greater growth hormone synthesis. For example, some scientists point to studies that have investigated potential synergism between similar compounds.

For example, one study examined a CJC-1295 analog and GHRP-2, reporting that each peptide individually may have led to a 20-fold and 47-fold increase, respectively, in the pulsatile secretion of growth hormone from anterior pituitary somatotroph cells.^[17] However, when both compounds were applied simultaneously, the increase in growth hormone secretion may have reached 54-fold, suggesting a possible synergistic interaction. More research is needed to investigate the potential synergy between CJC-1295 and GHRP-2 and how it may be affected by the addition of Ipamorelin.

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. Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005 Jul;146(7):3052-8. doi: 10.1210/en.2004-1286. Epub 2005 Apr 7. PMID: 15817669.
2. 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.
3. Berlanga-Acosta J, Abreu-Cruz A, Herrera DGB, Mendoza-Marí Y, Rodríguez-Ulloa A, García-Ojalvo A, Falcón-Cama V, Hernández-Bernal F, Beichen Q, Guillén-Nieto G. Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects. Clin Med Insights Cardiol. 2017 Mar 2;11:1179546817694558. doi: 10.1177/1179546817694558. PMID: 28469491; PMCID: PMC5392015.
4. Himpe E, Kooijman R. Insulin-like growth factor-I receptor signal transduction and the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathway. Biofactors. 2009 Jan-Feb;35(1):76-81. doi: 10.1002/biof.20. PMID: 19319849.
5. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006 Mar;91(3):799-805. doi: 10.1210/jc.2005-1536. Epub 2005 Dec 13. PMID: 16352683.
6. Gobburu, J. V., Agersø, H., Jusko, W. J., & Ynddal, L. (1999). Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharmaceutical research, 16(9), 1412–1416. https://doi.org/10.1023/a:1018955126402
7. Veldhuis, J. D., Keenan, D. M., Bailey, J. N., Adeniji, A. M., Miles, J. M., & Bowers, C. Y. (2009). Novel relationships of age, visceral adiposity, insulin-like growth factor (IGF)-I and IGF binding protein concentrations to growth hormone (GH) releasing-hormone and GH releasing-peptide efficacies in men during experimental hypogonadal clamp. The Journal of clinical endocrinology and metabolism, 94(6), 2137–2143. https://doi.org/10.1210/jc.2009-0136
8. Bowers, C. Y., Granda, R., Mohan, S., Kuipers, J., Baylink, D., & Veldhuis, J. D. (2004). Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women. The Journal of clinical endocrinology and metabolism, 89(5), 2290–2300. https://doi.org/10.1210/jc.2003-031799
9. 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
10. Laferrère, Blandine, et al. “Growth hormone-releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.” The Journal of Clinical Endocrinology and Metabolism vol. 90,2 (2005): 611-4.
11. Johansen PB, Nowak J, Skjaerbaek C, Flyvbjerg A, Andreassen TT, Wilken M, Orskov H. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res. 1999 Apr;9(2):106-13. doi: 10.1054/ghir.1999.9998. PMID: 10373343.
12. 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.
13. 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
14. Hu R, Wang Z, Peng Q, Zou H, Wang H, Yu X, Jing X, Wang Y, Cao B, Bao S, Zhang W, Zhao S, Ji H, Kong X, Niu Q. Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation. PLoS One. 2016 Feb 19;11(2):e0149461. doi: 10.1371/journal.pone.0149461. PMID: 26894743; PMCID: PMC4760683.
15. Andersen, N. B., Malmlöf, K., Johansen, P. B., Andreassen, T. T., Ørtoft, G., & Oxlund, H. (2001). The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation in adult rats. Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society, 11(5), 266–272. https://doi.org/10.1054/ghir.2001.0239
16. Sacheck, J. M., Ohtsuka, A., McLary, S. C., & Goldberg, A. L. (2004). IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. American journal of physiology. Endocrinology and metabolism, 287(4), E591–E601. https://doi.org/10.1152/ajpendo.00073.2004
17. 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

BPC-157 is a fully synthetic peptide consisting of 15 amino acids, classifying it as a pentadecapeptide. Also known as L 14736, PL-10, and Bepecin, this molecule has garnered scientific interest for its potential to interact with intracellular signaling pathways, possibly influencing mechanisms involved in tissue repair and regeneration. Studies suggest that it may promote angiogenesis—the formation of new blood vessels—and modulate inflammatory responses. Experimental models have indicated that BPC-157 might aid in protecting and regenerating various cell types and tissues, highlighting its potential in laboratory research.^[1]

TB-500 is a laboratory-engineered peptide designed to mimic the functions of thymosin beta-4 (Tβ4), a peptide naturally produced in most cells, but especially the cells of the thymus gland. Thymosin beta-4 is known for its involvement in crucial cellular activities such as cell migration, differentiation, and tissue repair. Composed of 43 amino acids encoded by the TMSB4X gene, its specific amino acid sequence is arranged as SDKPDMAEI EKFDKSKLKK TETQEKNPLP SKETIEQEKQ AGES. Scientific research has explored the potential of TB-500 to modulate vital biological processes. It is believed to interact with various signaling pathways within cells, possibly influencing their behavior and promoting functions essential for tissue healing. Similar to BPC 157, TB-500 is also under research for its potential to support angiogenesis and modulate inflammation signaling. Additionally, experimental models suggest that TB-500 may contribute to cellular and tissue regeneration in experimental models.^[2]

 

Overview

BPC-157 is a peptide that may influence several biological processes through different mechanisms:^[3]

• One possible pathway involves the modulation of nitric oxide (NO) synthesis. By interacting with the NO system, BPC-157 may conceivably protect endothelial cells—the cells lining the interior of blood vessels—and promote angiogenesis, which is the formation of new blood vessels.
• Additionally, BPC-157 might regulate the activity of cells responsible for tissue repair. It may support the expression of the early growth response 1 (EGR1) gene, which plays a role in producing cytokines and growth factors essential for tissue regeneration. This action may facilitate the early development of the extracellular matrix and stimulate collagen production.
• The peptide may also affect inflammatory responses and interact with proteins like nerve growth factor 1-A binding protein-2 (NGFI-A BP2), potentially leading to the suppression of certain factors involved in inflammation or tissue remodeling.

Thymosin beta-4 (TB-500) is thought to affect recovery and inflammation in experimental models through different pathways:

• The peptide may affect cell movement and the organization of the actin cytoskeleton by binding to globular actin (G-actin). This binding may modulate the assembly of actin filaments, which is essential for cellular migration—a vital process in wound healing and tissue repair.^[4,5]
• Scientific studies suggest that TB-500 may influence specific signaling pathways related to inflammation that are activated during tissue damage.^[6] In experimental cell models, TB-500 has been observed to potentially increase the expression of microRNA-146a (miR-146a), a small non-coding RNA molecule known to downregulate certain signaling pathways within cells. The upregulation of miR-146a appears to lead to a decrease in the levels of two pro-inflammatory cytokines: interleukin-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Both IRAK1 and TRAF6 play significant roles in mediating inflammatory responses.

 

Scientific and Research Studies

 

BPC-157 & TB-500 Blend and Connective Tissues

BPC-157 and TB-500 may have favorable potential on connective tissue cells, such as the cells that make up tendons and ligaments, potentially by interacting with the survival and migration of these cells, as well as the organization of extracellular structures.

For example, histological examination suggested that TB-500 might support the organization of collagen fibers within healing ligament tissues.^[7] In ligaments exposed to TB-500, the collagen fibers appeared regularly aligned and densely packed, oriented parallel to the ligament’s length. Conversely, ligaments from the control group seemed to exhibit disorganized collagen bundles with irregular spacing. Transmission electron microscopy (TEM) observations indicated that TB-500 could increase the diameter and uniformity of collagen fibrils, which are the smaller strands composing collagen fibers within granulation tissue. In the experimental group, these collagen fibrils appeared thicker and more uniformly distributed compared to those in the controls. Biomechanical testing, which assesses the mechanical strength and elasticity of tissues, suggested that TB-500 might support the functional recovery of connective tissues. Ligaments from the experimental group showed higher values of the maximum stress the tissue may withstand before failure compared to the controls, indicating a possible improvement in mechanical integrity.

Additionally, scientists hypothesized that the peptide BPC-157 might support the outgrowth of tendon fibroblast cells from tendon tissue samples cultured in vitro.^[8] The experimental results in tendon explants suggested that “BPC 157 markedly increased the in vitro migration of tendon fibroblasts […] as revealed by transwell filter migration assay.” The support of cell migration and spreading suggests that BPC-157 may influence the dynamics of the cell’s cytoskeleton. At the molecular level, BPC-157 may activate the signaling pathway involving focal adhesion kinase (FAK) and paxillin, proteins that play key roles in cell adhesion and migration. Western blot analysis, a laboratory technique used to detect specific proteins, indicated that BPC-157 increased the phosphorylation levels (activation states) of FAK and paxillin proteins without changing their total protein amounts. Since the FAK-paxillin pathway is involved in cell movement and attachment, this activation might explain the observed increase in fibroblast motility. Furthermore, BPC-157 seemed to increase cell survival under oxidative stress induced by hydrogen peroxide (H₂O₂).

There is insufficient research to suggest whether BPC-157 and TB-500 may potentiate each other’s actions, but considering their differences in mechanisms of action, it is widely considered to be possible.

 

BPC-157 & TB-500 Blend and Angiogenesis

Both BPC-157 & TB-500 are posited to interact with various growth factors that affect angiogenesis – the process of new blood vessel formation.

For example, in vitro studies suggest that BPC-157 might stimulate the expression of the early growth response gene-1 (egr-1), which is posited to induce the transcription of various cytokines and growth factors, which could contribute to angiogenesis.^[9] The peptide apparently led to increased levels of egr-1 mRNA and protein shortly after stimulation, which may indicate a mechanism for promoting endothelial growth factors. This early expression of egr-1 might result in the production of factors that facilitate extracellular matrix formation and tissue regeneration. Since the formation of new blood vessels is a critical component of granulation tissue development, BPC-157’s action on egr-1 and subsequent growth factor induction may suggest its potential role in facilitating new blood vessel formation.

Research involving murine models of critical limb ischemia suggests that overexpression of TB-500 may also increase the viability, angiogenesis, and migratory ability of endothelial cells.^[10] This action appears to be mediated by the upregulation of angiogenesis-related factors such as angiopoietin-2 (Ang2), TEK receptor tyrosine kinase 2 (tie2), and vascular endothelial growth factor A (VEGFA). Moreover, TB-500 may influence the Notch/NF-κB signaling pathways, which are posited to play roles in vascular development and angiogenesis. The overexpression of TB-500 apparently increased the expression of key components of these pathways, including the NOTCH1 intracellular domain (N1ICD), Notch receptor 3 (Notch3), NF-κB, and phosphorylated p65. The potential involvement of these pathways was further suggested by observations that inhibitors of the Notch and NF-κB pathways reversed the actions of TB-500 on angiogenesis-related factors. TB-500 overexpression may have also led to increased expression of markers associated with blood vessel formation, such as CD31 and α-smooth muscle actin (α-SMA). This suggests that TB-500 may potentially support capillary and arteriolar densities.

 

BPC-157 & TB-500 Blend Actions on Nerve Cell Signaling

While research on TB-500 is scarce, there are several BPC-157 experiments suggesting that the peptide may interact with neurotransmitters and how different nerve cells interact. Studies involving murine models suggest that BPC-157 might influence both serotonin and dopamine systems.^[11] It may affect the release of serotonin in specific regions of the nervous system, particularly within the nigrostriatal pathway—a neural circuit associated with movement control and reward mechanisms. Evidence indicates that BPC-157 may impact akinesia (loss of voluntary movement) and catalepsy (muscle rigidity and fixed posture), which are linked to impaired dopamine function.

Additionally, BPC-157 might exhibit neuroprotective actions on nerve cells. In other murine models, it appears to protect sensory neurons and promote the regeneration of peripheral nerves after injury.^[12] It might also counteract the progression of neuronal injury by possibly reducing neuron death, loss of myelin sheath, and cyst formation in nerve tissue. These actions may be related to BPC-157’s influence on neurotransmitter systems and its interaction with signaling pathways involving genes like Egr-1 and its co-repressor NAB2. The peptide may also interact with other neurotransmitter systems, including those involving gamma-aminobutyric acid (GABA) and opioid receptor signaling. Thus, the peptide may lessen both immediate and long-term disturbances caused by neurotropic and neurotoxic agents, which might be connected to its interactions with the various signaling systems.

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. Seiwerth S, Milavic M, Vukojevic J, Gojkovic S, Krezic I, Vuletic LB, Pavlov KH, Petrovic A, Sikiric S, Vranes H, Prtoric A, Zizek H, Durasin T, Dobric I, Staresinic M, Strbe S, Knezevic M, Sola M, Kokot A, Sever M, Lovric E, Skrtic A, Blagaic AB, Sikiric P. Stable Gastric Pentadecapeptide BPC 157 and Wound Healing. Front Pharmacol. 2021 Jun 29;12:627533. doi: 10.3389/fphar.2021.627533. PMID: 34267654; PMCID: PMC8275860.
2. Maar, K., Hetenyi, R., Maar, S., Faskerti, G., Hanna, D., Lippai, B., Takatsy, A., & Bock-Marquette, I. (2021). Utilizing Developmentally Essential Secreted Peptides Such as Thymosin Beta-4 to Remind the Adult Organs of Their Embryonic State-New Directions in Anti-Aging Regenerative Therapies. Cells, 10(6), 1343. https://doi.org/10.3390/cells10061343
3. Sikiric P, Seiwerth S, Rucman R, Turkovic B, Rokotov DS, Brcic L, Sever M, Klicek R, Radic B, Drmic D, Ilic S, Kolenc D, Stambolija V, Zoricic Z, Vrcic H, Sebecic B. Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157. Curr Med Chem. 2012;19(1):126-32. doi: 10.2174/092986712803414015. PMID: 22300085.
4. Huff T, Müller CS, Otto AM, Netzker R, Hannappel E. beta-Thymosins, small acidic peptides with multiple functions. Int J Biochem Cell Biol. 2001 Mar;33(3):205-20. doi: 10.1016/s1357-2725(00)00087-x. PMID: 11311852.
5. Sanders MC, Goldstein AL, Wang YL. Thymosin beta 4 (Fx peptide) is a potent regulator of actin polymerization in living cells. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4678-82. doi: 10.1073/pnas.89.10.4678. PMID: 1584803; PMCID: PMC49146.
6. Santra M, Zhang ZG, Yang J, Santra S, Santra S, Chopp M, Morris DC. Thymosin β4 up-regulation of microRNA-146a promotes oligodendrocyte differentiation and suppression of the Toll-like proinflammatory pathway. J Biol Chem. 2014 Jul 11;289(28):19508-18. doi: 10.1074/jbc.M113.529966. Epub 2014 May 14. PMID: 24828499; PMCID: PMC4094061.
7. Xu B, Yang M, Li Z, Zhang Y, Jiang Z, Guan S, Jiang D. Thymosin β4 enhances the healing of medial collateral ligament injury in rat. Regul Pept. 2013 Jun 10;184:1-5. doi: 10.1016/j.regpep.2013.03.026. Epub 2013 Mar 21. PMID: 23523891.
8. 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.
9. 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.
10. Lv, S., Cai, H., Xu, Y., Dai, J., Rong, X., & Zheng, L. (2020). Thymosin‑β 4 induces angiogenesis in critical limb ischemia mice via regulating Notch/NF‑κB pathway. International journal of molecular medicine, 46(4), 1347–1358. https://doi.org/10.3892/ijmm.2020.4701
11. 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.
12. 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.

Pinealon is a synthetic tripeptide composed of the amino acids L-glutamic acid, L-aspartic acid, and L-arginine (Glu-Asp-Arg)1. It is categorized as a peptide bioregulator because it has been hypothesized to interact directly with cellular DNA and influence gene expression, a property not commonly observed in peptide compounds.

Research has associated Pinealon with a range of impacts on cellular processes, particularly behavior modulation, and has suggested its role in cellular protection under hypoxic (low oxygen) conditions. Given its possible influence on the pineal gland, Pinealon has drawn scientific interest for its potential impact on physiological processes involving compound metabolism, circadian rhythm regulation, memory retention, and cognitive functions.

 

Mechanisms of Action

Pinealon peptide appears to exhibit a distinctive mechanism of action compared to other peptides. Unlike most peptides that rely on surface or cytoplasmic receptor interactions, Pinealon appears to bypass these conventional pathways. Due to its small molecular size, Pinealon peptide is believed to penetrate lipid bilayers, enabling it to cross both cellular and nuclear membranes and gain direct access to DNA.

Experimental studies^[2], including research on HeLa cell models, suggest that Pinealon’s potential to permeate cellular barriers permits direct engagement with nuclear DNA. This direct DNA interaction indicates that Pinealon may function as a modulator of gene expression, a feature that might underlie its broad impacts independent of typical receptor-mediated pathways.

 

Scientific and Research Studies

 

Pinealon Peptide and Circadian Rhythm Modulation

Pinealon peptide has been observed in early research to play a potential role in modulating the sleep-wake cycle and associated physiological behaviors. Findings indicate that Pinealon may help counteract dysfunctions induced by circadian disruptions. This peptide has appeared promising to researchers studying possible re-establishing baseline function of the pineal gland during circadian rhythm disturbances, potentially enhancing sleep quality, behavioral stability, blood pressure regulation, and associated physiological parameters.

According to researchers^[3], the research implication of bio-regulating peptides “was found to restore the organism’s adaptive potential, [better-supported] psychoemotional indices, intensified resistance to work stress and reduced occupational risk of borderline [cognitive] disorders.” The connection between sleep regulation and cellular aging processes has been well-documented in scientific studies, with disrupted sleep patterns thought to possibly affect cognitive function, cardiovascular function, wound recovery, and other areas, collectively accelerating cellular aging.

Pinealon’s capacity to potentially mitigate sleep disturbances may offer a promising approach to attenuate the cellular age-related impacts of poor sleep.

 

Pinealon Peptide and Regulation of Caspase-3 to Mitigate Cellular Apoptosis

Preliminary studies on Pinealon’s potential cellular impacts, particularly in ischemic stroke models in rats, suggest it may influence key cytokine signaling pathways that regulate caspase-3 enzyme levels. Caspase-3 is integral in triggering apoptosis, the programmed process of cell death. By modulating caspase-3 activity, Pinealon peptide may disrupt the progression of apoptosis, potentially reducing cell damage under conditions of oxygen deprivation, as observed in stroke-related cellular stress.

The role of caspase-3 extends beyond neural tissue and is present across various cell types. Studies using myocardial infarction models indicate that Pinealon peptide may reduce caspase-3 expression after a cardiac event, hinting at its potential to attenuate cellular apoptosis linked to post-myocardial infarction tissue remodeling.^[4]

Furthermore, studies on dermal cells suggest Pinealon’s said ability to downregulate caspase-3 expression, where it appears to decrease apoptosis and support cell proliferation. This reduction in apoptotic activity may support better-supported regenerative processes, promoting cellular resilience and repair in diverse tissue types.^[5]

 

Pinealon Peptide and Neuroprotective Mechanisms

Research in prenatal rat models suggests that Pinealon peptide may offer neuroprotection by reducing oxidative stress, potentially supporting cognitive function and motor coordination. Studies report a marked decrease in reactive oxygen species (ROS) accumulation and necrotic cell count within the brain, implying that Pinealon may protect neurons from cell death.

Additionally, Pinealon’s observed impacts on ROS reduction and necrotic cell mitigation suggest that it may interact with the cell genome directly. Specifically, research indicates that “Pinealon is able to interact directly with the cell genome,” highlighting that while lower concentrations of Pinealon may primarily restrict ROS accumulation and cell mortality, higher concentrations appear to modulate the cell cycle directly.^[6]

Data further indicates that Pinealon peptide may promote cell cycle modulation by activating pathways associated with cellular proliferation. In oxidative stress conditions, this modulation does not necessarily increase cell count but may counteract some adverse impacts of ROS. Follow-up studies in adult rat models under hypoxic conditions further support the neuroprotective potential of Pinealon. This impact is thought to result from the activation of innate antioxidant systems and suppression of excitotoxicity linked to N-methyl-D-aspartate (NMDA), which has been associated with neuronal damage in cases of traumatic brain injury, ischemic stroke, and neurotoxicity from over-activation, such as in alcohol withdrawal contexts.^[7]

Moreover, Pinealon peptide has been linked to elevated levels of irisin, a peptide involved in neural differentiation, cell proliferation, and energy management within the brain. Irisin, traditionally associated with muscular tissue protection, has been recently detected in the brain, where it appears to influence gene expression in the hippocampus.^[8]

Further studies in brain cortex cell cultures have suggested that Pinealon peptide may support the expression of 5-tryptophan hydroxylase through epigenetic changes. This enzyme, crucial for serotonin synthesis and release, may underlie Pinealon’s potential neuroprotective and geroprotective potential.^[9]

 

Pinealon Peptide and Neuroprotective Anti-Cellular Aging Potential

Pinealon peptide is hypothesized to possess neuroprotective anti-aging properties within the central nervous system. Research originating in Russia suggests that Pinealon, along with the peptide Vesugen, may exhibit anabolic impacts in neural tissue, potentially slowing biological markers of cellular aging within the brain.^[10]

Beyond its impact on neural cells, Pinealon peptide appears to influence a range of cellular processes. Studies indicate that Pinealon may affect muscle cell function by modulating the expression of irisin, a peptide linked to cellular resilience during physical exertion, fat oxidation, and telomere maintenance. By supporting irisin stability, Pinealon may indirectly protect telomere length, a critical factor in cellular aging and oxidative stress resistance.

Plasma irisin levels, which are thought to be associated with telomere length in functional adults, are positively impacted by calorie restriction. In fact, restriction of calorie intake is one of the few actions for which researchers have documented impacts for the extension of cellular longevity and overall biological function. Emerging data^[11] also suggests that irisin may function beyond the context of muscle cells. This finding indicates that Pinealon’s potential anti-aging impacts may have widespread action. Some of these may potentially extend to brain function.

 

Pinealon Peptide and Impacts on Prenatal Hyperhomocysteinemia

Hyperhomocysteinemia, a condition characterized by elevated levels of the amino acid homocysteine (HC) in the bloodstream, is often indicative of severe vitamin deficiencies and has been linked to an increased risk of neurological decline. A recent study^[12] aimed at investigating the potential impacts of Pinealon peptide in experimentally induced hyperhomocysteinemia in pregnant murine models. In this study, methionine was introduced to female murine models beginning in their second trimester, leading to elevated HC concentrations. Researchers then evaluated the offspring from both control and experimental groups.

Findings like these have suggested that, while Pinealon peptide did not appear to reduce or mitigate elevated homocysteine levels in the offspring, there did appear to be observable evidence of better-supported cognitive performance in the experimental group. Researchers concluded that, although Pinealon may not directly influence homocysteine metabolism, it might reduce the compound’s toxic impacts, offering a possible avenue for protecting cognitive function in conditions associated with hyperhomocysteinemia.

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. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 10273502, Pinealon Peptide. https://pubchem.ncbi.nlm.nih.gov/compound/Pinealon.
2. Fedoreyeva LI, Kireev II, Khavinson VKh, Vanyushin BF. Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA. Biochemistry (Mosc). 2011 Nov;76(11):1210-9. doi: 10.1134/S0006297911110022. PMID: 22117547. https://pubmed.ncbi.nlm.nih.gov/22117547/
3. Bashkireva AS, Artamonova VG. [The peptide correction of neurotic disorders among professional truck drivers]. Adv Gerontol. 2012;25(4):718-28. Russian. PMID: 23734521. https://pubmed.ncbi.nlm.nih.gov/23734521/
4. Zhang J, Zhang W. Can irisin be a linker between physical activity and brain function? Biomol Concepts. 2016 Aug 1;7(4):253-8. doi: 10.1515/bmc-2016-0012. PMID: 27356237. https://pubmed.ncbi.nlm.nih.gov/27356237/
5. Khavinson, V.K., Lin’kova, N.S., Tarnovskaya, S.I. et al. Short Peptides Stimulate Serotonin Expression in Cells of Brain Cortex. Bull Exp Biol Med 157, 77–80 (2014). https://doi.org/10.1007/s10517-014-2496-y
6. Khavinson V, Ribakova Y, Kulebiakin K, Vladychenskaya E, Kozina L, Arutjunyan A, Boldyrev A. Pinealon peptide increases cell viability by suppression of free radical levels and activating proliferative processes. Rejuvenation Res. 2011 Oct;14(5):535-41. doi: 10.1089/rej.2011.1172. Epub 2011 Oct 6. PMID: 21978084. https://pubmed.ncbi.nlm.nih.gov/21978084/
7. Kozina LS. [Investigation of anti-hypoxic properties of short peptides]. Adv Gerontol. 2008;21(1):61-7. Russian. PMID: 18546825. https://pubmed.ncbi.nlm.nih.gov/18546825/
8. Zhang J, Zhang W. Can irisin be a linker between physical activity and brain function? Biomol Concepts. 2016 Aug 1;7(4):253-8. doi: 10.1515/bmc-2016-0012. PMID: 27356237. https://pubmed.ncbi.nlm.nih.gov/27356237/
9. Khavinson, V.K., Lin’kova, N.S., Tarnovskaya, S.I. et al. Short Peptides Stimulate Serotonin Expression in Cells of Brain Cortex. Bull Exp Biol Med 157, 77–80 (2014). https://doi.org/10.1007/s10517-014-2496-y
10. Meshchaninov VN, Tkachenko EL, Zharkov SV, Gavrilov IV, Katyreva IuE. [Effect Of Synthetic Peptides On Aging Of Patients With Chronic Polymorbidity And Organic Brain Syndrome Of The Central Nervous System In Remission]. Adv Gerontol. 2015;28(1):62-7. Russian. PMID: 26390612. https://pubmed.ncbi.nlm.nih.gov/26390612/
11. Khavinson VKh, Kuznik BI, Tarnovskaya SI, Lin’kova NS. Short Peptides and Telomere Length Regulator Hormone Irisin. Bull Exp Biol Med. 2016 Jan;160(3):347-9. doi: 10.1007/s10517-016-3167-y. Epub 2016 Jan 8. PMID: 26742748. https://pubmed.ncbi.nlm.nih.gov/26742748/
12. Arutjunyan A, Kozina L, Stvolinskiy S, Bulygina Y, Mashkina A, Khavinson V. Pinealon peptide protects the rat offspring from prenatal hyperhomocysteinemia. Int J Clin Exp Med. 2012;5(2):179-85. Epub 2012 Apr 6. PMID: 22567179; PMCID: PMC3342713. https://pmc.ncbi.nlm.nih.gov/articles/PMC3342713/

Semaglutide is a synthetic analog of the glucagon-like peptide-1 (GLP-1), an endogenous hormone consisting of 30 amino acids. The primary role of GLP-1 appears to support insulin secretion, lower blood glucose levels, and preserve pancreatic beta cells by stimulating insulin gene transcription. Additionally, it has been posited to delay gastric emptying, leading to appetite suppression. GLP-1 appears to impact several critical organs, including the heart, kidneys, lungs, and liver.

Like the endogenous GLP-1 peptide, Semaglutide, as a GLP-1 receptor agonist, has been researched for its potential to reduce blood glucose levels and decrease appetite.^[1] Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced in the intestines, primarily in response to nutrient ingestion. Research suggests that it plays a critical role in the regulation of glucose homeostasis, particularly in postprandial (after caloric intake) conditions. GLP-1 appears to stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner, potentially facilitating cellular glucose uptake and contributing to the reduction of blood glucose levels.

 

Mechanisms of Action

Studies suggest that there are two main ways through which the peptide may function:

Endogenous GLP-1: Endogenous GLP-1 is secreted following food intake. It slows gastric emptying, mitigates hunger hormone signals, and promotes insulin release when blood glucose levels are elevated. This physiological process aids in both glucose and weight regulation by reducing appetite and caloric intake.

GLP-1 Receptor Agonists: Synthetic GLP-1 receptor agonists have been developed in the course of diabetes research. These compounds appear to mimic the impacts of endogenous GLP-1 by activating its receptors on pancreatic beta cells, thereby increasing insulin secretion. They may also suppress glucagon release, further aiding in blood glucose regulation. Additionally, these agonists are considered to delay gastric emptying and mitigate hunger hormone signals, making them relevant to researchers studying the reduction of adipose tissue in laboratory models of type 2 diabetes.

The additional mechanism pathways include:

• Through binding with the GLP-1 receptors, Semaglutide may promote insulin secretion, i.e., glucose-dependent insulin release.^[2]
• Semaglutide is thought to support pancreatic beta cell function, supporting the proinsulin-to-insulin ratio.^[3]
• By delaying gastric emptying and reducing appetite, the compound may contribute to weight reduction.^[4]

 

Scientific and Research Studies

 

Semaglutide (GLP-1) Peptide and the Incretin Effect

Research suggests that the Semaglutide (GLP-1) peptide theoretically displays ‘the incretin effect.’ ‘The Incretin Effect’ is a physiological response mediated by gastrointestinal hormones released post-caloric intake to reduce blood glucose levels.

GLP-1 receptors located on pancreatic beta cells appear to bind with Semaglutide. This is intended to stimulate insulin secretion and aid in glucose control.

According to J.J. Holst, “The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions.”^[1] As a GLP-1 receptor agonist, Semaglutide appears to promote incretin hormone activity and, therefore, may have a hand in the regulation of blood sugar levels.

 

Semaglutide (GLP-1) Peptide and Pancreatic Beta Cell Protection

Research suggests that Semaglutide (GLP-1) peptide has the potential to protect pancreatic beta cells, as seen in a study^[5] conducted on non-obese diabetic (NOD) mice models. In this experiment, mice were introduced to Semaglutide in combination with lisofylline, an immunomodulatory agent that suppresses autoimmune activity, and exendin-4, a compound regarded for its proposed ability to promote beta cell proliferation. Based on the results, it appeared that Semaglutide might stimulate pancreatic beta-cell growth and mitigate beta-cell apoptosis (cell death).

Furthermore, results also suggested that the mice maintained optimal glucose levels up to 145 days post-introduction, even after discontinuation of the Semaglutide (GLP-1) peptide. Because of these long-lasting impacts, it is speculated that Semaglutide may have enduring relevance to glucose regulation and beta cell preservation.

 

Semaglutide (GLP-1) Peptide and Appetite Suppression

GLP-1 receptor agonists, including Semaglutide, appear to impact appetite regulation through the delay of gastric motility. This potentially leads to a prolonged feeling of fullness, thereby reducing overall food intake.^[1] Research^[6] suggests that Semaglutide, when introduced in the brain, may reduce the neural drive to consume calories, possibly leading to a decrease in appetite and better-supporting mitigation of hunger hormone signals.

Experimental studies in murine models suggest that Semaglutide’s central action curtails food intake, potentially making it an agent in the reduction of excessive adipose tissue. It is also speculated that over time, Semaglutide may result in gradual weight reduction, possibly contributing to better-supported cardiovascular function and increased energy levels.

 

Semaglutide (GLP-1) Peptide and Neurological Research

Semaglutide, through its action on GLP-1 receptors (GLP-1R), is suggested to possess neuroprotective and cognition-supporting properties. GLP-1 and its receptors are expressed in brain cells, and deficiencies in GLP-1R are associated with seizures, impaired learning, and neuronal damage. Research by Mathew J. During et al. highlights that “Systemic administration of GLP-1 receptor agonists in wild-type animals [may] prevent kainate-induced apoptosis of hippocampal neurons. Brain GLP-1R represents a promising new target for cognitive-enhancing and neuroprotective agents.”^[7]

Additionally, studies^[8] have posited that Semaglutide (GLP-1) peptide may protect hippocampal regions of the brain from cellular apoptosis, indicating their potential in addressing neurodegenerative conditions such as Alzheimer’s disease. Furthermore, Semaglutide also appears to reduce beta-amyloid concentrations, which are thought to be linked to the development of Alzheimer’s. Some research posits a possibility that the peptide may contribute to the delay or reversal of some symptoms of neurodegeneration.

 

Semaglutide (GLP-1) Peptide and Cardiovascular Function

Studies suggest that GLP-1 receptors are distributed throughout the cardiovascular system, where their activation appears to play a crucial role in maintaining cardiac function.^[9] It appears that Semaglutide, through its theorized action on GLP-1 receptors, may help regulate blood pressure and reduce left ventricular diastolic pressure, both of which are deemed essential in mitigating cardiac hypertrophy and related cardiovascular complications.

Additionally, Semaglutide (GLP-1) peptide is speculated to support glucose uptake in muscle cells specific to muscular tissue in the cardiovascular system, particularly in ischemic or weakened myocardial tissue following a heart attack. Better-supported glucose metabolism appears to further support cardiac function and may aid in reversing the adverse impacts of myocardial infarction.

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. Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide is a glucagon-like peptide-1 receptor agonist with cardiovascular benefits for the management of type 2 diabetes. Rev Endocr Metab Disord. 2022 Jun;23(3):521-539. doi: 10.1007/s11154-021-09699-1. Epub 2022 Jan 7. PMID: 34993760; PMCID: PMC8736331. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8736331/#:~:text=Semaglutide%20improves%20the%20efficiency%20of,as%20postprandial%20glucose%20%5B26%5D
2. Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019 Apr 12;10:155. doi: 10.3389/fendo.2019.00155. PMID: 31031702; PMCID: PMC6474072. https://pubmed.ncbi.nlm.nih.gov/31031702/
3. Ahmann AJ, Capehorn M, Charpentier G, Dotta F, Henkel E, Lingvay I, Holst AG, Annett MP, Aroda VR. Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial. Diabetes Care. 2018 Feb;41(2):258-266. doi: 10.2337/dc17-0417. Epub 2017 Dec 15. PMID: 29246950. https://pubmed.ncbi.nlm.nih.gov/29246950/
4. Christou GA, Katsiki N, Blundell J, Fruhbeck G, Kiortsis DN. Semaglutide is a promising anti-obesity drug. Obes Rev. 2019 Jun;20(6):805-815. doi: 10.1111/obr.12839. Epub 2019 Feb 15. PMID: 30768766. https://pubmed.ncbi.nlm.nih.gov/30768766/
5. Yang Z, Chen M, Carter JD, Nunemaker CS, Garmey JC, Kimble SD, Nadler JL. Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes. Biochem Biophys Res Commun. 2006 Jun 9;344(3):1017-22. doi: 10.1016/j.bbrc.2006.03.177. Epub 2006 Apr 5. PMID: 16643856. https://pubmed.ncbi.nlm.nih.gov/16643856/
6. Blonde L, Klein EJ, Han J, Zhang B, Mac SM, Poon TH, Taylor KL, Trautmann ME, Kim DD, Kendall DM. Interim analysis of the effects of exenatide treatment on A1C, weight, and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab. 2006 Jul;8(4):436-47. doi: 10.1111/j.1463-1326.2006.00602.x. PMID: 16776751. https://pubmed.ncbi.nlm.nih.gov/16776751/
7. During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN. The glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003 Sep;9(9):1173-9. doi: 10.1038/nm919. Epub 2003 Aug 17. PMID: 12925848. https://pubmed.ncbi.nlm.nih.gov/12925848/
8. Perry T, Haughey NJ, Mattson MP, Egan JM, Greig NH. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J Pharmacol Exp Ther. 2002 Sep;302(3):881-8. doi: 10.1124/jpet.102.037481. PMID: 12183643. https://pubmed.ncbi.nlm.nih.gov/12183643/
9. Gros R, You X, Baggio LL, Kabir MG, Sadi AM, Mungrue IN, Parker TG, Huang Q, Drucker DJ, Husain M. Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology. 2003 Jun;144(6):2242-52. doi: 10.1210/en.2003-0007. PMID: 12746281. https://pubmed.ncbi.nlm.nih.gov/12746281/

AOD 9604 is described as a synthetic peptide derived from the C-terminal portion of the native growth hormone (GH). It is specifically derived from the last 15 amino acids (residues 177–191) of GH, with an additional tyrosine residue attached at the N-terminus, making it a peptide composed of 16 amino acids. Moreover, the AOD 9604 structure retains a disulfide bridge found between the two cysteine amino acids in the complete GH structure (Cys182 and Cys189), which in the case of AOD 9604 are at the 7th and 14th positions. The presence of a disulfide bridge between these two amino acids, combined with the addition of tyrosine at the N-terminus, is posited to significantly support AOD 9604 stability and bioavailability under conditions of extreme pH and exposure to various digestive enzymes.^[1]

AOD 9604 is thought to replicate the lipolytic actions of full-length GH while lacking the ability to influence carbohydrate metabolism, insulin-like growth factor-1 (IGF-1) production, or cellular growth and division. Therefore, the lipolytic activity of AOD 9604 appears to be limited to promoting fatty acid oxidation and increasing the breakdown of fat (lipolysis). Despite these proposed impacts, the exact mechanism through which AOD 9604 exerts its action is still not fully understood. It may not interact with the GH receptor, which suggests it may engage with β3-adrenergic receptors or other unidentified pathways to stimulate energy metabolism and potentially increase energy expenditure.^[2]

 

Mechanisms of Action

AOD 9604 peptide seems to activate several mechanisms involved in lipolysis, also referred to as lipolysis. These mechanisms might include both a direct stimulation of lipolysis in adipose cells (adipocytes) and an indirect increase in overall energy expenditure, potentially leading to greater calorie burn. One proposed mechanism is through modulating the expression of β3-adrenergic receptors (β3-AR), which are thought to be important receptors that promote lipolysis in adipose cells. AOD 9604 peptide appears to influence β3-AR mRNA expression, possibly increasing the sensitivity of adipocytes to signals that stimulate lipolysis.

In studies involving obese murine models, AOD 9604 peptide was suggested to increase lipolysis, which seemed to coincide with increased β3-AR mRNA expression. This observation suggests that AOD 9604 peptide might elevate levels of these receptors in adipocytes, potentially supporting the cells’ responsiveness to catecholamines, which are hormones that play a role in promoting lipolysis. In obese murine models, where β3-AR levels are generally reduced compared to lean mice, AOD 9604 appeared to restore β3-AR expression to levels similar to those seen in lean animals.

The role of β3-AR in the actions of AOD 9604 was further explored in studies using murine models lacking β3-AR (β3-AR knockout mice). In these knockout models, AOD 9604 did not result in increased lipolysis, unlike in normal (wild-type) models, which implies that β3-AR might be important for the chronic fat-reducing impacts of AOD 9604 peptide. However, in short-term experiments, AOD 9604 still seemed to increase energy expenditure and fat oxidation in the knockout murine models, although the potential was less pronounced compared to wild-type animals. This suggests that while β3-AR may play a significant role in the long-term lipolytic impacts of AOD 9604, the compound may also activate other β3-AR-independent pathways that influence energy metabolism and utilization of fat stores.^[3]

 

Scientific and Research Studies

 

AOD 9604 Peptide and Lipolysis in Adipocytes

AOD 9604 peptide has been suggested to reduce adipose tissue accumulation by more than 50% in laboratory models, possibly by supporting the rate of lipolysis. Research suggests that the peptide may support lipolysis by about 23%.^[4] This support is indicated by an increase in glycerol release, which serves as a marker of lipid breakdown. Researchers have linked this impact to the activation of hormone-sensitive lipase (HSL), a crucial enzyme responsible for breaking down stored triglycerides into free fatty acids and glycerol.

This action results in the reduction of adipocyte size. Additionally, it is proposed that AOD 9604 may also inhibit acetyl-CoA carboxylase, an enzyme involved in the synthesis of fatty acids. This suggests that AOD 9604 peptide not only promotes lipolysis but may also mitigate the formation of new fat, thus reducing overall fat storage. The researchers concluded that “The present findings reveal for the first time that the synthetic lipolytic domain [may be] capable of reducing weight gain” in experimental models.

Further research indicates that the impacts of AOD 9604 peptide on HSL and acetyl-CoA carboxylase may be linked to intracellular signaling pathways.^[5] Studies have indicated that AOD 9604 induces a biphasic release of diacylglycerol (DAG) in fat cells, similar to the impacts of GH. This suggests that AOD 9604 might share some signaling mechanisms with the growth hormone. The production of DAG is associated with the activation of protein kinase C (PKC), which is believed to regulate both lipolysis and other metabolic processes involved in lipid management.

Another experiment also suggested that AOD 9604 peptide may have been associated with a significant rise in fat oxidation, particularly in obese murine models where a 216% increase in fat oxidation was observed. This suggests that AOD 9604 not only stimulates the breakdown of stored triglycerides and lipolysis but also facilitates the exposure of these liberated fatty acids to cells as an energy source, further decreasing lipid storage in adipocytes.^[6]

 

AOD 9604 Peptide and Fat Storage in Adipocytes

As mentioned, AOD 9604 peptide may have anti-lipogenic impacts in isolated adipose tissues. In particular, studies with adipose tissue samples suggest that AOD 9604 may reduce the incorporation of glucose into lipid molecules, thus possibly decreasing the rate of de novo lipogenesis, which is the synthesis of fatty acids from non-lipid sources such as carbohydrates.^[5]

In other words, the reduction in adipocytes of various sizes seen with AOD 9604 peptide in lab models may be due to a general suppression of lipid accumulation mechanisms. Specifically, the researchers reported that “A reduction in lipogenesis and a stimulation in lipolysis were observed. These alterations led to decreased rates of lipid storage and increased rates of lipid mobilization from adipose tissue. These changes, in turn, led to the size reduction in adipocyte cell size.” This outcome was reflected by the reduction of the number of large adipocytes and a shift toward smaller adipocytes.

Findings like this one suggest that AOD 9604 peptide may regulate hypertrophy in adipocytes (enlargement) by modulating both anabolic (constructive) and catabolic (destructive) processes of lipid metabolism. This combined action of promoting lipolysis while inhibiting lipogenesis is likely to lead to a net reduction in lipid content within adipocytes, contributing to a decrease in their overall size.

 

AOD 9604 Peptide and Other Research Objectives

Researchers have also explored the potential of AOD 9604 in models of osteoarthritis and its potential actions on tumor cells. For instance, one trial modeled AOD 9604 with and without hyaluronic acid (HA) in a collagenase-induced osteoarthritis model.^[7] The morphological and histopathological scores, which indicate the extent of cartilage degeneration, were apparently lower in the AOD 9604 groups. The combination of AOD 9604 and HA indicated potentially synergistic actions. Specifically, the AOD 9604 peptide and HA group suggest reduced signs of cartilage degradation compared to the other groups.

This suggests that AOD 9604 peptide might influence cartilage through mechanisms similar to growth hormone by promoting proteoglycan and collagen production, though in a way that does not involve IGF-1. HA, believed to act as a chondroprotective agent, may also have supported these relevant impacts, possibly supporting the residence time of AOD 9604 in the joint or contributing to its bioactive properties. The study emphasized that while AOD 9604 suggested promise in supporting cartilage regeneration, the exact mechanisms by which it exerts these impacts are not well understood.

AOD 9604 peptide has displayed promising potential in increasing the potential of anti-cancer cell agents like doxorubicin’s ability to bind to critical breast tumor cell receptors such as the progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2).^[8] These receptors are pivotal in the progression of these tumor cells, and better-supported binding suggests that doxorubicin may more impactfully target and interfere with cancer cell functions. By loading both AOD 9604 and doxorubicin into Chitosan nanoparticles, the study achieved a delivery system that supports doxorubicin’s potential.

In vitro studies on MCF-7 breast tumor cells indicated that the dual-loaded nanoparticles were more impactful in killing these cells than nanoparticles containing doxorubicin alone, as observed in data that displays comparatively lower IC50 values. The presence of AOD 9604 peptide may support how tumor cells take up doxorubicin or alter how similar agents interact inside the cells, leading to increased tumor cell death. By supporting delivery specifically to tumor cells, AOD 9604 may help reduce the off-target impacts of doxorubicin, minimizing damage to functional cells.

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. Isidro ML, Cordido F. Approved and Off-Label Uses of Obesity Medications, and Potential New Pharmacologic Treatment Options. Pharmaceuticals (Basel). 2010 Jan 12;3(1):125-145. doi: 10.3390/ph3010125. PMID: 27713245; PMCID: PMC3991023.
2. Cox HD, Smeal SJ, Hughes CM, Cox JE, Eichner D. Detection and in vitro metabolism of AOD9604. Drug Test Anal. 2015 Jan;7(1):31-8. doi: 10.1002/dta.1715. Epub 2014 Sep 10. PMID: 25208511.
3. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001 Dec;142(12):5182-9. doi: 10.1210/endo.142.12.8522. PMID: 11713213.
4. Ng FM, Sun J, Sharma L, Libinaka R, Jiang WJ, Gianello R. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res. 2000;53(6):274-8. doi: 10.1159/000053183. PMID: 11146367.
5. Ng FM, Jiang WJ, Gianello R, Pitt S, Roupas P. Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. J Mol Endocrinol. 2000 Dec;25(3):287-98. doi: 10.1677/jme.0.0250287. PMID: 11116208.
6. Heffernan MA, Thorburn AW, Fam B, Summers R, Conway-Campbell B, Waters MJ, Ng FM. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord. 2001 Oct;25(10):1442-9. doi: 10.1038/sj.ijo.0801740. PMID: 11673763.
7. Kwon DR, Park GY. Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model. Ann Clin Lab Sci. 2015 Summer;45(4):426-32. PMID: 26275694.
8. Habibullah MM, Mohan S, Syed NK, Makeen HA, Jamal QMS, Alothaid H, Bantun F, Alhazmi A, Hakamy A, Kaabi YA, Samlan G, Lohani M, Thangavel N, Al-Kasim MA. Human Growth Hormone Fragment 176-191 Peptide Enhances the Toxicity of Doxorubicin-Loaded Chitosan Nanoparticles Against MCF-7 Breast Cancer Cells. Drug Des Devel Ther. 2022 Jun 27;16:1963-1974. Doi: 10.2147/DDDT.S367586. PMID: 35783198; PMCID: PMC92493