A more direct study from Xu et al looked at how TB500 accelerates overall rates of wound healing. A prokaryotic vector harboring two complete Tβ4 genes with a short linker was constructed and expressed in Escherichia coli. A pilot-scale fermentation (10 L) was performed to produce engineered bacteria and the Tβ4 dimer was purified by one-step hydrophobic interaction chromatography. The activities of the Tβ4 dimer to promote endothelial cell proliferation, migration, and sprouting were assessed by tetramethylbenzidine (methylthiazol tetrazolium), trans-well, scratch, and tube formation assays. The ability to accelerate dermal healing was assessed on rats. After fermentation, the Tβ4 dimer accounted for about 30% of all the bacteria proteins. The purity of the Tβ4 dimer reached 98% after hydrophobic interaction chromatography purification. An average of 562.4 mg/L Tβ4 dimer was acquired using a 10 L fermenter. In each assay, the dimeric Tβ4 exhibited enhanced activities compared with native Tβ4. Notably, the ability of the dimeric Tβ4 to promote cell migration was almost two times higher than that of Tβ4. The rate of dermal healing in the dimeric Tβ4-treated rats was approximately 1 day faster than with native Tβ4-treated rats. The dimeric Tβ4 exhibited enhanced activity on wound healing than native Tβ4, and the purification process was simple and cost-effective. This data could be of significant benefit for the high pain and morbidity associated with chronic wounds disease. A better strategy to develop Tβ4 as a treatment for other diseases caused by injuries such as heart attack, neurotrophic keratitis, and multiple sclerosis was also described (9.) Even further studies show its ability to further increase strength, endurance, and reduce inflammation. Sosne et al states within their abstract “Thymosin beta 4 (Tβ4) is a low molecular weight protein present in all cells except erythrocytes. Although Tβ4 is the major monomeric actin-sequestering peptide in cells and can depolymerize F-actin, evidence is mounting to support the idea that it has multiple, seemingly diverse, cellular functions. In cornea, as in other tissues, Tβ4 promotes cell migration and wound healing, has anti-inflammatory properties, and suppresses apoptosis. In this review we discuss the current state of knowledge regarding the effects of Tβ4 in maintaining the healthy, functional cornea. The clinical implications of the use of Tβ4 as a wound healing and anti-inflammatory agent are discussed.” Read more about TB500’s role in inflammation and other beneficial properties below in the reference section (10.)
In conclusion, these two peptides have a tremendous ability to help up-regulate healing rates (however their long term effectiveness and side effects have yet to be determined.) In terms of practical application, many literature and anecdotal evidence reports show that dosing BPC-157 at 1-10mcgs per kg of body weight daily and TB500 at 2mgs twice per week to be a very effective starting point. Your optimal dosage will completely be dependent on how well or how poorly you metabolize these compounds so some trial and error will be required. BPC-157 is systemic where as TB500 should be applied as close to the injured area as possible. Now go out, read more literature on these two amazing peptides, and make an informed decision for yourself as to whether or not this is something that can benefit your athletic and recovery endeavors.
References
BPC 157 has been given even more attention for its other benefits. Sikiric et al looked at the counteraction by stable gastric pentadecapeptide BPC 157 with NSAIDs (3.) They stated “recently, we claim that BPC 157 may be used as an antidote against NSAIDs. We focused on BPC 157 beneficial effects on stomach, duodenum, intestine, liver and brain injuries, adjuvant arthritis, pain, hyper/hypothermia, obstructive thrombus formation and thrombolysis, blood vessel function, counteraction of prolonged bleeding and thrombocytopenia after application of various anticoagulants and antiplatelet agents and wound healing improvement. The arguments for BPC 157 antidote activity (i.e., the role of BPC 157 in cytoprotection, being a novel mediator of Robert’s cytoprotection and BPC 157 beneficial effects on NSAIDs mediated lesions in the gastrointestinal tract, liver and brain and finally, counteraction of aspirin-induced prolonged bleeding and thrombocytopenia) obviously have a counteracting effect on several established side-effects of NSAIDs use. The mentioned variety of the beneficial effects portrayed by BPC 157 may well be a foundation for establishing BPC 157 as a NSAIDs antidote since no other single agent has portrayed a similar array of effects. Unlike NSAIDs, a very high safety (no reported toxicity (LD1 could be not achieved)) profile is reported for BPC 157. Also, unlike the different dosage levels of aspirin, as a NSAIDs prototype, which differ by a factor of about ten, all these beneficial and counteracting effects of BPC 157 were obtained using the equipotent dosage (μg, ng/kg) in parenteral or peroral regimens.” BPC 157 is also linked to reversing systemic corticosertoid impaired muscle healing, accelerating bone healing, and repairing inflammatories diseases (4, 5, 6, 7.)
With the proven efficacy of BPC-157, we can now move into TB500. TB500 is the synthetic form of Thymosin Beta-4 that is specifically designed to help deal with injuries in athletes (Thymosin Beta-4 is a naturally occurring peptide present in our cells that plays a pivotal role in building new blood vessels, new small muscle tissue fibers, cell migration and blood cell reproduction.) Its main ability to up-regulate actin (and other cell building proteins) is what allows it to promote cell migration and proliferation as well as increases the circulation to injuries areas (thereby accelerating healing rates.) In fact, Wei et al looked into how thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy. Pulmonary hypertension (PH) is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH) and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC) dysfunction and pulmonary arterial smooth muscle cell (PASMC) proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (Tβ4) is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether Tβ4 has any protective role in PH. The purpose of this study is to evaluate the whether Tβ4 can be used as a vascular-protective agent. In monocrotaline (MCT)-induced PH mouse model, we showed that mice treated with Tβ4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that Tβ4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Their study may provide pre-clinical evidence for Tβ4 and may consider as vasculo-protective agent for the treatment of PH induced RVH (8.)
References
One common thing among many top athletes is injury. In any aspect of life when you are continuously pushing your body’s limits, stress and strain creep up, and injury can occur. Due to this, we look into optimizing our nutrition and training strategies to increase healing rates, but, sometimes it just isn’t fast enough. In this situation, after the cause of the injury is assessed and nutrition and training are adjusted, adding in peptides can make a tremendous amount of difference in the acceleration of your healing capabilities (and some people may even add them in after surgeries to once again decrease the time they need to spend out of the gym.) In this cause, there are two peptides I want to cover completely in depth within this three part series. Those being BPC-157 and TB500. These peptides are simply a sequence of amino acids linked in a chain, the carboxyl group of each acid being joined to the amino group of the next . Let us first look at some of the promising effects of both compounds before moving into practical application.
BPC-157 will be our first peptide to cover, mainly because I feel it is the superior option if having to chose between the two. Beginning with a study from Chang et al, we see its promotion of tendon and ligament healing. This study was designed to investigate the potential mechanism of BPC 157 to enhance healing of injured tendon. The outgrowth of tendon fibroblasts from tendon explants cultured with or without BPC 157 was examined. Results showed that BPC 157 significantly accelerated the outgrowth of tendon explants. Cell proliferation of cultured tendon fibroblasts derived from rat Achilles tendon was not directly affected by BPC 157 as evaluated by MTT assay. However, the survival of BPC 157-treated cells was significantly increased under the H(2)O(2) stress. BPC 157 markedly increased the in vitro migration of tendon fibroblasts in a dose-dependent manner as revealed by transwell filter migration assay. BPC 157 also dose dependently accelerated the spreading of tendon fibroblasts on culture dishes. The F-actin formation as detected by FITC-phalloidin staining was induced in BPC 157-treated fibroblasts. The protein expression and activation of FAK and paxillin were determined by Western blot analysis, and the phosphorylation levels of both FAK and paxillin were dose dependently increased by BPC 157 while the total amounts of protein was unaltered. In conclusion, BPC 157 promotes the ex vivo outgrowth of tendon fibroblasts from tendon explants, cell survival under stress, and the in vitro migration of tendon fibroblasts, which is likely mediated by the activation of the FAK-paxillin pathway (1.) Even more so is its ability to have tendon to bone healing effects. The abstract from Krivic et al states “Stable gastric pentadecapeptide BPC 157 (BPC 157, as an antiulcer agent in clinical trials for inflammatory bowel disease; PLD-116, PL 14736, Pliva, no toxicity reported) alone (without carrier) ameliorates healing of tendon and bone, respectively, as well as other tissues. Thereby, we focus on Achilles tendon-to-bone healing: tendon to bone could not be healed spontaneously, but it was recovered by this peptide. After the rat’s Achilles tendon was sharply transected from calcaneal bone, agents [BPC 157 (10 microg, 10 ng, 10 pg), 6alpha-methylprednisolone (1 mg), 0.9% NaCl (5 mL)] were given alone or in combination [/kg body weight (b.w.) intraperitoneally, once time daily, first 30-min after surgery, last 24 h before analysis]. Tested at days 1, 4, 7, 10, 14, and 21 after Achilles detachment, BPC 157 improves healing functionally [Achilles functional index (AFI) values substantially increased], biomechanically (load to failure, stiffness, and Young elasticity modulus significantly increased), macro/microscopically, immunohistochemistry (better organization of collagen fibers, and advanced vascular appearance, more collagen type I). 6alpha-Methylprednisolone consistently aggravates the healing, while BPC 157 substantially reduces 6alpha-methylprednisolone healing aggravation. Thus, direct tendon-to-bone healing using stabile nontoxic peptide BPC 157 without a carrier might successfully exchange the present reconstructive surgical methods” (2.)
References