B7-33 6mg

                                    B7-33 Peptide

B7-33 is a soluble synthetic single-chain peptide obtained from the larger, naturally occurring protein H2-relaxin, which is considered to induce pleiotropic actions impacting the musculoskeletal system, cardiovascular system, and reproduction.^[1] B7-33 appears to retain the anti-fibrotic properties of Relaxin without enhancing cAMP production, it may also stimulate ERK1/2 phosphorylation and promote matrix metalloproteinase 2 (MMP2) expression and the degradation of extracellular collagen. The Relaxin family of peptides has four endogenous receptors divided into two pairs (RXFP1/2 and RXFP3/4).^[2] The function of these receptors is under scientific study, with researchers theorizing that:

RXFP-1: Considered to influence sperm motility, pregnancy, vascular endothelium, and joint health.
RXFP-2: May affect testicular descent.
RXFP-3: Mutations of this receptor may affect schizotypal personality disorder and certain sleep disturbances.
RXFP-4: The role of this receptor is not clear. It is suggested to be expressed on sperm and appears to alter insulin-like peptide 5, which in turn may regulate hunger/satiation signaling.

The Relaxin receptors appear to be stimulated by cAMP, orexin, corticotropin-releasing factor (CRF), several insulin-like peptides, and GLP-1. The agonists have been observed to exhibit anti-inflammatory, antioxidant, and wound-healing potential. Research suggests that Relaxin exhibits all the same properties apart from vasodilators, blood vessel growth stimulators, and anti-hypertrophics.

B7-33 PEPTIDE FUNCTION
Researchers have suggested that “B7-33 represents the first functionally selective agonist of […] RXFP1.” They also suggest that while H2 relaxin seems to also activate RXFP2, B7-33 does not appear to influence cAMP activity in HEK-RXFP2 cells. B7-33 seemingly shows high potency in increasing the activity of the collagen-degrading enzyme metalloproteinase (MMP)-2 in cardiac fibroblasts and murine renal myofibroblasts, which may play a role in fibrosis prevention Still, this potency was apparently blocked by an RXFP1-specific antagonist. It appears that B7-33 could have potently activated pERK1/2, leading researchers to conclude that B7-33 might be a functionally selective agonist of RXFP1. Furthermore, studies suggested that both H2 relaxin and B7-33 might exert their biological activity through RXFP1 and potentially through RXFP1–AT2R heterodimers. Moreover, B7-33 appears to stimulate the pERK pathway over the cAMP pathway preferentially.^[3] The pERK pathway regulates cell cycle arrest in the G1 phase and has been implicated in several diseases like Alzheimer’s and Creutzfeldt-Jakob. By blocking cell cycle progression in cells with RXFP1 receptors, B7-33 appears to exercise anti-fibrotic potential through the proposed ability to stimulate RXFP1-angiotensin II type 2 receptor heterodimering, which activates pERK1/2 signaling and thus triggers the increased production of the collagen-degrading enzyme matrix metalloproteinase (MMP) -2. B7-33 has exhibited some potential in activating pERK1/2 in fibroblasts, which could possibly be due to a supposed coupling of ERK1/2 to RXFP1 in these cells. Based on some speculation, there’s a possibility that B7-33 might serve as a potential anti-fibrotic agent while having limited activity at cAMP pathways.
Tests were conducted on B7-33 for its potential on a murine model of heart damage. From these tests, it appeared to exhibit anti-fibrotic activity, which seemed somewhat comparable to H2 relaxin. In addition to previous findings, B7-33 appeared to display an anti-remodeling and anti-fibrotic potential in a murine model of chronic allergic reaction. It has been hypothesized that the binding of B7-33 to RXFP1 may mediate anti-fibrotic actions through a pERK1/2-neuronal nitric oxide (NO) synthase (nNOS)-NO-cGMP-dependent pathway, which could potentially inhibit myofibroblast differentiation and excessive ECM/collagen deposition. Similar to H2 relaxin, it seems that B7-33 might stimulate MMPs associated with collagen degradation and potentially signal through constitutive RXFP1–AT2R heterodimers. Lastly, even though B7-33 appears to have high potency, it is largely unstructured in solution, which could suggest that it may adopt the correct conformation for binding upon interaction with RXFP1. Researchers also note that, in contrast to H2 relaxin, B7-33 does not appear to promote tumor cell growth.