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Thymosin Beta
Wednesday, August 14th, 2019

Thymosin is a hormone secreted by the thymus gland. This powerful hormone serves a vital role in the training and development of a special type of white blood cell known as T-lymphocytes or T cells. In addition, thymosin also assists in the development of antibodies necessary for a strong immune system. The predominant form of thymosin known as thymosin beta 4 is an actin, a multi-functional protein that helps muscles and cells move. Thymosin beta 4 also plays a crucial role in tissue regeneration and protection.

Overall Health Benefits of Thymosin Beta

Boosts Immune System

Thymosin increases the levels of white blood cells and antibodies, thus strengthening the immune system and protecting against a wide array of diseases. Its predominant form thymosin beta 4 has been shown to heighten the immune response through the following important mechanisms:

  1. In human gingival fibroblasts (tissues of the gums), thymosin beta 4 suppresses the section of the proinflammatory cytokine interleukin 8 (IL8) and protects against programmed cell death (apoptosis) induced by tumor necrosis factor-α.[1]
  2. In human colon, thymosin beta 4 modulates the function of lymphocytes. [2]
  3. In a murine model, thymosin beta 4 potently inhibits white blood cell infiltration and significantly decreases the levels of pro-inflammatory cytokines. [3]
  4. Thymosin beta 4 facilitates the recognition of a variety of molecular targets, thus making it easier to detect harmful microorganisms. [4]
  5. Thymosin beta 4 is involved in the production of hemocytes, which are cells that play a crucial role in the immune system of invertebrates. [5]
  6. Thymosin beta appears to have antiviral properties. [6]
  7. Thymosin beta 4 enhances the ability of antibodies to bind with antigens (toxins or other foreign substances) to easily destroy foreign invaders and remove them from the body. [7]
  8. Thymosin beta 4 enhances natural killer cells’ cytotoxicity. [8]
  9. Thymosin beta 4 is involved in stabilin-2-mediated engulfment of cells that trigger apoptosis.[9]
  10. In patients with uremia (build-up of waste products in the kidneys), thymosin beta appears to have restorative effect on depressed lymphocyte response. [10]
  11. Phase I and Phase II clinical trials with thymosin in the treatment of primary immunodeficiency diseases, autoimmune diseases, and cancer have shown that this hormone exerts its therapeutic benefits by maintaining immune balance and preventing thymus gland malfunction. [11]

Improves Heart Health

The human heart can repair itself at a very slow pace. However, muscle and tissue damage caused by a heart attack cannot be repaired. Interestingly, numerous studies show that thymosin beta 4 could be sufficiently used to improve heart health and regenerate heart damage:

  1. In mammals, thymosin beta 4 administration prevents death of heart muscle cells, stimulates vessel growth, and activates heart stem cells to initiate regeneration. [12]
  2. In patients with acute ST segment elevation myocardial infarction (STEMI), transplantation of heart stem cells pre-treated with thymosin beta 4 improves exercise capacity and left ventricular function. [13]
  3. In patients with ischemic heart disease, a condition that affects blood supply to the heart, thymosin beta 4 administration promotes migration and survival of heart muscle cells. [14]
  4. In rats, thymosin beta 4 reduces the levels of harmful free radicals in heart muscle cells. [15]
  5. In mice, thymosin beta 4 treatment improves left ventricular function after myocardial infarction. [16]
  6. In mice, thymosin beta 4 reduces inflammatory cell infiltration and promotes cardiac wound healing. [17]
  7. In pigs, thymosin beta 4 appears to reduce rejection after heart transplantation.[18]

 

Improves Liver Health

Because of its potent regenerative properties, thymosin beta 4 has also been studied for its therapeutic effect on various liver disorders. Studies show that thymosin beta 4 exerts this effect through the following mechanisms:

  1. Thymosin beta 4 suppresses the activation of hepatic stellate cells (HSCs), which are the main matrix-producing cells in the process of liver fibrosis (scarring). [19]
  2. Thymosin beta 4 has anti-inflammatory and anti-scarring properties which help prevent liver scarring and damage. [20-21]
  3. Thymosin beta 4 stimulates liver regeneration through promotion of liver cell migration, blood vessel formation, cell survival, and stem cell maturation. [22]
  4. In patients with chronic hepatitis B combined with non-alcoholic fatty liver disease (NAFLD), thymosin beta 4 inhibits oxidative stress and proinflammatory factors. [23]
  5. Thymosin beta 4 inhibits the production of substances that cause liver scarring. [24]

Accelerates Wound Healing

Emerging evidence suggests that thymosin beta 4 is involved in a wide range of cellular responses that helps accelerate wound healing:

  1. In both normal and aged rodents, thymosin beta 4 acts by increasing angiogenesis (development of new blood vessels) and cell migration in damaged tissues. [25]
  2. In a rat full thickness wound model, thymosin beta 4 administration increases formation of granulation tissues, collagen deposition, and angiogenesis. [26]
  3. In diabetic mice, thymosin beta 4 improves angiogenesis by activating the VEGF/AKT pathway. [27]
  4. In mice, thymosin beta 4 administration improves wound healing markers such as wound closure, granulation, and vascularization. [28]

Improves Eye Health

Studies show that thymosin beta 4 may help maintain eye health by protecting against injury and accelerating the eye’s regenerative process:

  1. In cultured human corneal epithelial cells, thymosin beta 4 treatment significantly decreases the levels of proinflammatory substances and accelerates the wound healing process after injury. [29-30]
  2. In diabetic patients, treatment with 2 drops 4 times daily of thymosin beta 4 for 4 weeks appears to heal diabetic corneal defects. [31]
  3. In animals with severe traumatic corneal wound disorders, thymosin beta administration promotes rapid corneal wound healing and decreases infiltration of inflammatory substances. [32]
  4. In patients with moderate to severe dry eye, administration of thymosin beta 4 ophthalmic solution significantly relieves signs and symptoms. [33]

Promotes Nerve Regeneration

Thymosin beta 4 is widely distributed in the nervous system, suggesting that it has a role in nerve protection and regeneration. Numerous studies show that thymosin beta 4 is beneficial in several types of nerve injuries:

  1. In mice with brain inflammation, thymosin beta 4 improves functional recovery by reducing inflammatory infiltrates and stimulating oligodendrogenesis (formation of protective covering of nerve cells or neurons). [34]
  2. In rats with spinal cord injury, thymosin beta 4 treatment is associated with a significant decrease in proinflammatory cytokines and spinal lesions. [35]
  3. In animals, thymosin beta 4 plays a crucial role in stem cell maturation and in regeneration and repair of injuries. [36]

Improves Brain Health

With thymosin beta 4’s role in tissue regeneration and protection., it seems logical that this powerful protein may also be beneficial in supporting brain health. Numerous studies found that thymosin beta 4 may actually help protect against stroke and other brain injuries:

  1. In mice, thymosin beta 4 stimulates regeneration and formation of new blood vessels.
  2. In rats with ischemic stroke (caused by a blood clot), treatment with thymosin beta 4 significantly improves neurological functional outcome. [38-39]
  3. In a rat model of ischemic stroke, thymosin beta 4 administration improves neurological functional outcome by stimulating oligodendrogenesis. [40]
  4. In patients with stroke and other neurological diseases, thymosin beta 4 treatment appears to remodel or rebuild the nervous system by stimulating self-healing processes in the brain, spinal cord, and nerves. [41]
  5. In animal models of traumatic brain injury (TBI,) early (6 hours post injury) treatment with thymosin beta 4 at doses of 6 and 30 mg/kg reduces brain lesions and cell loss and improves functional recovery. [42]

 

 

Improves Lung Health

The anti-scarring properties of thymosin beta 4 may also play a role in maintaining lung health. In mice, thymosin beta 4 administration helps counter bleomycin-induced lung damage by suppressing inflammation and preventing lung scarring. [43]

Normalizes Blood Sugar Levels

Not only does thymosin beta 4 protects against nerve injury caused by diabetes, but it also helps stabilize blood sugar levels. [44] In diabetic mice, thymosin beta 4 ameliorates high blood sugar levels (hyperglycemia) and improves insulin resistance. [45]

Improves Blood Pressure

The ability of thymosin to train and develop T cells may also have a positive effect on blood pressure not just on immune function. In mammals, studies show that administration of thymosin induces the growth of T cell population and thus reduce the autoimmune state, thereby reducing blood pressure. [46]

References:

  1. Reti R, Kwon E, Qiu P, Wheater M, Sosne G. Thymosin beta4 is cytoprotective in human gingival fibroblasts. European journal of oral sciences. 2008; 116(5):424-30. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18821984.
  2. Elitsur Y, Mutchnick MG, Sakr WA, Luk GD. Thymosin alpha 1 and thymosin beta 4 modulate human colonic lamina propria lymphocyte function. Immunopharmacology. ; 20(2):89-96. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/2266003.
  3. Sosne G, Chan CC, Thai K, et al. Thymosin beta 4 promotes corneal wound healing and modulates inflammatory mediators in vivo. Exp Eye Res. 2002;74:293–9. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11950239.
  4. Bubb MR. Thymosin beta 4 interactions. Vitamins and hormones. 2003; 66:297-316. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/12852258.
  5. Li J, Zhang Y, Liu Y. A thymosin beta-4 is involved in production of hemocytes and immune defense of Hong Kong oyster, Crassostrea hongkongensis. Developmental and comparative immunology. 2016; 57:1-9. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26695126.
  6. Retrieved from https://www.sciencedirect.com/science/article/pii/S0145305X15000713.
  7. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2012.06659.x/abstract.
  8. Lee HR, Yoon SY, Kang HB. Thymosin beta 4 enhances NK cell cytotoxicity mediated by ICAM-1. Immunology letters. 2009; 123(1):72-6. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19369144.
  9. Lee SJ, So IS, Park SY, Kim IS. Thymosin beta4 is involved in stabilin-2-mediated apoptotic cell engulfment. FEBS letters. 2008; 582(15):2161-6. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18519035.
  10. Abiko T, Sekino H. Synthesis of a thymosin beta 4-like peptide, deacetyl-thymosin beta Xen4, and its restorative effect on depressed lymphocyte blastogenic response to phytohemagglutinin (PHA) in uremic patients. Chemical & pharmaceutical bulletin. 1989; 37(9):2467-71. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/2605693.
  11. Low TL, Thurman GB, Chincarini C. Current status of thymosin research: evidence for the existence of a family of thymic factors that control T-cell maturation. Annals of the New York Academy of Sciences. 1979; 332:33-48. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/394636.
  12. Shrivastava S, Srivastava D, Olson EN, DiMaio JM, Bock-Marquette I. Thymosin beta4 and cardiac repair. Annals of the New York Academy of Sciences. 2010; 1194:87-96. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20536454.
  13. Zhu J, Song J, Yu L. 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; 18(8):1037-42. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27288307.
  14. Crockford D. Development of thymosin beta4 for treatment of patients with ischemic heart disease. Annals of the New York Academy of Sciences. 2007; 1112:385-95. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17947592.
  15. Kumar S, Gupta S. Thymosin beta 4 prevents oxidative stress by targeting antioxidant and anti-apoptotic genes in cardiac fibroblasts. PloS one. 2011; 6(10):e26912. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22046407.
  16. Retrieved from https://transmedcomms.biomedcentral.com/articles/10.1186/s41231-016-0008-y.
  17. Evans MA, Smart N, Dubé KN, et al. Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing. Nature communications. 2013;4:2081. doi:10.1038/ncomms3081. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22046407.
  18. Postrach J, Schmidt M, Thormann M. Adeno-associated viral vector 2.9 thymosin ß4 application attenuates rejection after heart transplantation: results of a preclinical study in the pig. Transplantation. 2014; 98(8):835-43. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25321165.
  19. Kim J, Jung Y. Potential Role of Thymosin Beta 4 in Liver Fibrosis. Haybaeck J, ed. International Journal of Molecular Sciences. 2015;16(5):10624-10635. doi:10.3390/ijms160510624. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463665/.
  20. Jiang Y, Han T, Zhang Z-G, et al. Potential role of thymosin beta 4 in the treatment of nonalcoholic fatty liver disease. Chronic Diseases and Translational Medicine. 2017;3(3):165-168. doi:10.1016/j.cdtm.2017.06.003. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643779/.
  21. Schirmacher P., Geerts A., Pietrangelo A., Dienes H.P., Rogler C.E. Hepatocyte growth factor/hepatopoietin a is expressed in fat-storing cells from rat liver but not myofibroblast-like cells derived from fat-storing cells. Hepatology. 1992;15:5–11. doi: 10.1002/hep.1840150103. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1530788.
  22. Philp D, Kleinman HK. Animal studies with thymosin beta, a multifunctional tissue repair and regeneration peptide. Annals of the New York Academy of Sciences. 2010; 1194:81-6. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20536453.
  23. Liang J., Cai W.J., Han T., Jing L., Ma Z., Gao Y. The expression of thymosin β4 in chronic hepatitis B combined nonalcoholic fatty liver disease. Medicine (Baltimore) 2016;95:e5763. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28033294.
  24. Mann J., Oakley F., Akiboye F., Elsharkawy A., Thorne A.W., Mann D.A. Regulation of myofibroblast transdifferentiation by DNA methylation and mecp2: Implications for wound healing and fibrogenesis. Cell Death Differ. 2007;14:275–285. doi: 10.1038/sj.cdd.4401979. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16763620.
  25. Philp D, Goldstein AL, Kleinman HK. Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development. Mechanisms of ageing and development. 2004; 125(2):113-5. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/15037013.
  26. Malinda KM, Sidhu GS, Mani H. Thymosin beta4 accelerates wound healing. The Journal of investigative dermatology. 1999; 113(3):364-8. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/10469335.
  27. Ti D, Hao H, Xia L. Controlled release of thymosin beta 4 using a collagen-chitosan sponge scaffold augments cutaneous wound healing and increases angiogenesis in diabetic rats with hindlimb ischemia. Tissue engineering. Part A. 2015; 21(3-4):541-9. Retrieves from https://www.ncbi.nlm.nih.gov/pubmed/25204972.
  28. Kim S, Kwon J. Thymosin beta 4 improves dermal burn wound healing via downregulation of receptor of advanced glycation end products in db/db mice. Biochimica et biophysica acta. 2014; 1840(12):3452-9. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25230158.
  29. Sosne G, Qiu P, Kurpakus-Wheater M. Thymosin beta 4: A novel corneal wound healing and anti-inflammatory agent. Clinical ophthalmology (Auckland, NZ). 2007;1(3):201-207. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25230158.
  30. Sosne G, Chan CC, Thai K. Thymosin beta 4 promotes corneal wound healing and modulates inflammatory mediators in vivo. Experimental eye research. 2001; 72(5):605-8. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11311052.
  31. Dunn SP, Heidemann DG, Chow CY. Treatment of chronic nonhealing neurotrophic corneal epithelial defects with thymosin beta4. Annals of the New York Academy of Sciences. 2010; 1194:199-206. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20536469.
  32. Sosne G, Szliter EA, Barrett R, Kernacki KA, Kleinman H, Hazlett LD. Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury. Experimental eye research. 2002; 74(2):293-9. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11950239.
  33. Sosne G, Ousler GW. Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAETM) model. Clinical Ophthalmology (Auckland, NZ). 2015;9:877-884. doi:10.2147/OPTH.S80954. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445951/.
  34. Zhang J, Zhang ZG, Morris D, et al. Neurological Functional Recovery After Thymosin Beta4 Treatment in Mice with Experimental Auto Encephalomyelitis. Neuroscience. 2009;164(4):1887-1893. doi:10.1016/j.neuroscience.2009.09.054. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784109/.
  35. Cheng P, Kuang F, Zhang H, Ju G, Wang J. Beneficial effects of thymosin β4 on spinal cord injury in the rat. Neuropharmacology. 2014; 85:408-16. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24937047.
  36. Goldstein AL, Kleinman HK. Advances in the basic and clinical applications of thymosin β4. Expert opinion on biological therapy. 2015; 15 Suppl 1:S139-45. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26096726.
  37. Morris DC, Chopp M, Zhang L, Zhang ZG. Thymosin beta4: a candidate for treatment of stroke? Annals of the New York Academy of Sciences. 2010; 1194:112-7. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20536457.
  38. Morris DC, Chopp M, Zhang L, Lu M, Zhang ZG. Thymosin beta4 improves functional neurological outcome in a rat model of embolic stroke. Neuroscience. 2010; 169(2):674-82. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20627173.
  39. Morris DC, Cui Y, Cheung WL. A dose-response study of thymosin β4 for the treatment of acute stroke. Journal of the neurological sciences. 2014; 345(1-2):61-7. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25060418.
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  42. Xiong Y, Mahmood A, Meng Y. Neuroprotective and neurorestorative effects of thymosin β4 treatment following experimental traumatic brain injury. Annals of the New York Academy of Sciences. 2012; 1270:51-8. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23050817.
  43. Conte E, Genovese T, Gili E. Protective effects of thymosin β4 in a mouse model of lung fibrosis. Annals of the New York Academy of Sciences. 2012; 1269:69-73. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23045972.
  44. Wang L, Chopp M, Szalad A. Thymosin β4 promotes the recovery of peripheral neuropathy in type II diabetic mice. Neurobiology of disease. 2012; 48(3):546-55. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22922221.
  45. Zhu J, Su LP, Ye L, Lee KO, Ma JH. Thymosin beta 4 ameliorates hyperglycemia and improves insulin resistance of KK Cg-Ay/J mouse. Diabetes research and clinical practice. 2012; 96(1):53-9. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22217673.
  46. Retrieved from https://www.google.com/patents/US4444757.
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