Thymosin Beta 4 (TB-500) Peptide
Thymosin beta 4 peptide is, along with its synthetic version TB-500, a subject of various studies aimed to uncover its mechanisms of action, potential uses, and benefits. This post focuses on the recent studies regarding thymosin beta 4 (TB-500) peptide and their findings.
Thymosin beta 4 inhibits activation and migration of hepatic stellate cells
Trans-differentiation of hepatic stellate cells is pivotal to the development of liver fibrosis, which is why preventing or reverting the activation, proliferation, and migration of these cells could lead to new therapies for the treatment of fibrosis or cirrhosis. Shah et al. carried out a study whose primary objective was to investigate the anti-fibrogenic effects of thymosin beta 4. For the purpose of the study, they used RT-PCR, Western blot, and proliferation and migration assays in early passages of hepatic stellate cells cultures treated with thymosin beta 4 peptides or PDGF-BB. Results of the study, published in the 2019 issue of the Expert Opinion on Biological Therapy, showed that the thymosin beta 4 peptide inhibits PDGF-BB induced activation of hepatic stellate cells activation and fibrogenesis as well as their proliferation and migration. It does so by blocking the phosphorylation of AKT at both S473 and T308 residues. Thymosin beta 4 exhibits its effects on the proliferation and migration of hepatic stellate cells through its actin-binding region by using the individual bioactive peptides of thymosin beta 4.
Anti-inflammatory potential of thymosin beta 4
Thymosin beta 4 is well-known for its anti-inflammatory potential, but further research is needed to elucidate this subject in greater detail. Current evidence shows this peptide could be of benefit to ameliorate inflammatory processes, but a lot more studies are needed to expand this topic. A review of available evidence published in July 2018 found that thymosin beta 4 has the potential to control inflammatory processes in the brain, thus opening new avenues for therapeutic applications to various neurodegenerative conditions.
Biomedical Reports published a study that examined whether thymosin beta 4 is a friend or foe to rheumatoid arthritis management. They concluded that although thymosin beta 4 plays several roles in the pathogenesis of rheumatoid arthritis, its mechanism of action is still not fully elucidated. In other words, at this point, it is still not certain whether the increased level of this peptide in serum and joint fluid of patients with rheumatoid arthritis has pro- or anti-inflammatory activities.
On the other hand, the research from PLoS One journal discovered that activation of thymosin beta 4 could be a therapeutic target for an inflammatory osteolytic disease like periodontitis. The activation of this peptide had anti-inflammatory effects via MAPK and NF-κB pathways in PDLCs.
The potential anti-inflammatory effects of thymosin beta 4 could aid management of various conditions, but also promote muscle recovery. This is particularly important if we bear in mind that inflammatory response to muscle injury may impair and prolong the process of recovery by limiting the repair of damaged tissue and triggering muscle atrophy. In fact, many people use TB-500 to enhance athletic performance and improve muscle recovery. However, this subject also requires further research.
Emerging evidence shows that thymosin beta 4 is a novel wound healing agent. Sosne et al. found it could promote corneal repair by suppressing apoptosis and exhibiting anti-inflammatory properties. Other studies have shown that the recombinant thymosin beta 4 poses as a cost-effective way to promote wound healing as well as to support endothelial cell proliferation, migration, capillary formation. It could have extensive applications in the diseases caused by the injury.
When discussing thymosin beta 4 it is also useful to mention its potential to address cardiovascular conditions. While the peptide is dubbed as effective for this purpose, current evidence is mixed. A study from the Frontiers in Pharmacology investigated whether thymosin beta 4 could treat the myocardial ischemia-reperfusion injury in pigs. The animals received either thymosin beta 4 or vehicle and underwent cardiopulmonary bypass and aortic clamping for 60 minutes. The results showed that the peptide did not decrease the quantity of cell death and despite promising previous trials this study didn’t confirm that thymosin beta 4 could have a positive effect on myocardial ischemia-reperfusion injury.
On the other hand, another study carried out a pilot clinical trial that demonstrated that thymosin beta 4 was effective in the treatment of patients after an acute ST-segment elevation myocardial infarction or heart attack. After six months of the study period, the left ventricular ejection fraction based on two measurements increased by 50%, while the stroke volume improved by 50% in the thymosin beta 4 pre-treated group. After a six-month follow-up, the average six-minute walking distance in participants improved by 14%. This was also the first human study that focused on the use of thymosin beta 4 in patients after a heart attack, and it showcases the potential clinical benefits of the peptide in repair and regeneration of damaged tissue to improve cardiac function.
Thymosin beta 4 and its synthetic version have the potential to alleviate inflammation and promote wound healing as well as to exhibit other positive effects on our health and wellbeing. Further studies are required to elucidate the full potential of this peptide.
Shah R, Reyes-Gordillo K, Rojkind M. Thymosin β4 inhibits PDGF-BB induced activation, proliferation, and migration of human hepatic stellate cells via its actin-binding domain. Expert Opin Biol Ther. 2018;18(sup1):177‐184. doi:10.1080/14712598.2018.1478961
Pardon MC. Anti-inflammatory potential of thymosin β4 in the central nervous system: implications for progressive neurodegenerative diseases. Expert Opinion on Biological Therapy 2018 Jul;18(sup1):165-169. Doi: 10.1080/14712598.2018.1486817
Kim KS, Yang HI. Thymosin β4 in rheumatoid arthritis: Friend or foe. Biomed Rep. 2017;7(3):205‐208. doi:10.3892/br.2017.952
Lee SI, Yi JK, Bae WJ, Lee S, Cha HJ, Kim EC. Thymosin Beta-4 Suppresses Osteoclastic Differentiation and Inflammatory Responses in Human Periodontal Ligament Cells. PLoS One. 2016;11(1):e0146708. Published 2016 Jan 20. doi:10.1371/journal.pone.0146708
Howard EE, Pasiakos SM, Blesso CN, et al. Divergent roles of inflammation in skeletal muscle recovery from injury. Frontiers in Physiology 2020 Feb. Doi:10.3389/fphys.2020.00087
Sosne G, Qiu P, Kurpakus-Wheater M. Thymosin beta 4: A novel corneal wound healing and anti-inflammatory agent. Clin Ophthalmol. 2007;1(3):201‐207.
Xu TJ, Wang Q, Ma XW, et al. A novel dimeric thymosin beta 4 with enhanced activities accelerates the rate of wound healing. Des Devel Ther. 2013;7:1075‐1088. Published 2013 Oct 1. doi:10.2147/DDDT.S50183
Stark CKJ, Tarkia M, Kentala R, et al. Systemic dosing of thymosin beta 4 before and after ischemia does not attenuate global myocardial ischemia-reperfusion injury in pigs. Frontiers in Pharmacology 2016 May. Doi:10.3389/fphar.2016.00115
Zhu J, Song J, Yu L, et al. Safety and efficacy of autologous thymosin β4 pre-treated endothelial progenitor cell transplantation in patients with acute ST-segment elevation myocardial infarction: a pilot study. Cytotherapy 2016 Aug;18(8):1037-1042. Doi: 10.1016/j.jcyt.2016.05.006