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▎TB500 fragment(17-13) Overview
The TB500 fragment (17-13) is an active fragment extracted from thymosin β4, consisting of seven amino acids. Its main mechanism of action is to bind to intracellular actin and regulate the function of actin, thereby influencing physiological processes such as the structure, movement, proliferation, and differentiation of cells.
Studies have shown that the TB500 fragment (17-13) has effects such as promoting wound healing, anti-inflammation, and enhancing cell regeneration. It can accelerate tissue repair, reduce the inflammatory response, promote angiogenesis, and improve musculoskeletal function.
In terms of applications, the TB500 fragment (17-13) has broad prospects in the field of tissue repair and regenerative medicine. It can be used to treat a variety of diseases, including burns, skin wounds, muscle injuries, and neurodegenerative diseases. Additionally, it can be applied to the research and development of anti-inflammatory drugs, providing new options for the treatment of inflammation-related diseases.
▎TB500 fragment(17-13) Structure
Source: PubChem | Sequence: LKKTETQ Molecular Formula: C36H66N10O13 Molecular Weight: 847.0 g/mol CAS Number: 476014-70-7 PubChem CID: 10169788 Synonyms: Fequesetide;HY-P2463;LKKTETQ |
▎TB500 fragment(17-13) Research
What are the mechanisms of action of TB500 fragment (17-13)?
1. Mechanisms of promoting tissue regeneration
The TB500 fragment (17-13) plays an important role in promoting tissue regeneration. It may achieve this function through the following mechanisms:
Stimulating cell proliferation and differentiation
This fragment may bind to specific receptors on the cell surface and activate the intracellular signaling pathways, thereby promoting cell proliferation and differentiation. For example, it may activate signaling pathways related to cell growth and division, such as the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway[1]. The activation of these pathways can promote the progression of the cell cycle, increase the number of cells, and thus promote tissue regeneration.
In addition, the TB500 fragment (17-13) may also promote cell differentiation by regulating the expression of specific genes. It may affect the activity of transcription factors related to cell differentiation, thereby regulating the differentiation of cells in a specific direction and providing different types of cells required for tissue regeneration.
Promoting angiogenesis
Tissue regeneration usually requires an adequate blood supply, and angiogenesis is a key process for providing blood supply. The TB500 fragment (17-13) may promote angiogenesis by stimulating the proliferation, migration, and lumen formation of vascular endothelial cells. It may activate the expression of pro-angiogenic factors such as vascular endothelial growth factor (VEGF), thus promoting the formation of new blood vessels[1]. The newly formed blood vessels can provide oxygen, nutrients, and growth factors to the damaged tissue, accelerating the tissue regeneration process.
2. Mechanisms of exerting anti-inflammatory effects
Inflammation is a defense response of the body to injury or infection, but excessive inflammatory response may lead to tissue damage and dysfunction. The TB500 fragment (17-13) has anti-inflammatory effects, and its mechanisms may include the following aspects:
Inhibiting the activation and recruitment of inflammatory cells
Inflammatory responses usually involve the activation and recruitment of various inflammatory cells, such as neutrophils, macrophages, and lymphocytes. The TB500 fragment (17-13) may reduce the inflammatory response by inhibiting the activation and recruitment of these inflammatory cells. For example, it may inhibit the expression of receptors on the surface of inflammatory cells, reducing the response of inflammatory cells to inflammatory signals; or by regulating the migration signals of inflammatory cells, reducing the recruitment of inflammatory cells to the damaged site [1].
In addition, this fragment may also affect the metabolic processes of inflammatory cells and inhibit the activity of inflammatory cells. For example, it may regulate the energy metabolism of inflammatory cells, reduce the production of reactive oxygen species (ROS) and pro-inflammatory cytokines by inflammatory cells, and thus reduce the inflammatory response.
Regulating the expression and release of inflammatory mediators
During the inflammatory response, a variety of inflammatory mediators are produced, such as cytokines, chemokines, and prostaglandins. These inflammatory mediators can further amplify the inflammatory response, leading to tissue damage. The TB500 fragment (17-13) may exert anti-inflammatory effects by regulating the expression and release of inflammatory mediators. For example, it may inhibit the expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6); and at the same time, promote the expression of anti-inflammatory cytokines, such as interleukin-10 (IL-10)[1].
In addition, this fragment may also affect the expression of chemokines, reducing the recruitment of inflammatory cells; or regulate the synthesis of prostaglandins, reducing the inflammatory response.
3. Mechanisms of achieving rapid repair
The mechanism of action of the TB500 fragment (17-13) in rapid repair may be closely related to its effects of promoting tissue regeneration and anti-inflammation. Specifically, it may achieve rapid repair through the following aspects:
Accelerating the synthesis and remodeling of the extracellular matrix
The extracellular matrix is an important part of tissues and is crucial for maintaining the structure and function of tissues. The TB500 fragment (17-13) may accelerate the repair of damaged tissues by promoting the synthesis of extracellular matrix components, such as collagen, elastin, and glycosaminoglycans. It may activate the signaling pathways related to the synthesis of the extracellular matrix, promoting cells to synthesize and secrete extracellular matrix components[1].
In addition, this fragment may also regulate the remodeling process of the extracellular matrix. During the tissue repair process, the extracellular matrix needs to be continuously remodeled to adapt to the growth and repair of tissues. The TB500 fragment (17-13) may control the balance between the degradation and synthesis of the extracellular matrix by regulating the activity of enzymes such as matrix metalloproteinases (MMPs), promoting the rapid repair of tissues.
Enhancing cell migration and adhesion ability
The migration and adhesion ability of cells are also very important for tissue repair. The TB500 fragment (17-13) may enhance the migration and adhesion ability of cells by regulating the expression and activity of cell surface receptors. For example, it may promote the expression of cell adhesion molecules such as integrins, increasing the adhesion between cells and the extracellular matrix; or regulate the reorganization of the cytoskeleton, promoting cell migration [1].
The migration of cells can enable the cells around the damaged tissue to quickly reach the damaged site and participate in the tissue repair process; and the adhesion of cells can ensure that the cells stably play a role at the damaged site, promoting the rapid repair of tissues.
HCD MS/MS recorded at 20eV (a) and 700MHz-NMR (b) spectra of TB-500.
Source:PubMed[1]
How does TB500 fragment (17-13) regulate the nervous system to improve athletic performance and reduce fatigue?
Direct action on neurons
The TB500 fragment (17-13) may directly act on neurons, affecting the excitability, synaptic transmission, and plasticity of neurons. For example, it may bind to receptors on the surface of neurons, activate intracellular signaling pathways, and regulate the function of neurons.
Some studies have shown that thymosin β4 can bind to a variety of receptors, including integrin receptors and growth factor receptors, which play important roles in the development and function of the nervous system[1].
Indirect regulation of the nervous system through the immune system
There is a close interaction between the immune system and the nervous system. The TB500 fragment (17-13) may indirectly affect the nervous system by regulating the function of the immune system. For example, it may affect the activity and secretion of immune cells, regulate the level of inflammatory factors, and thus affect the function of the nervous system.
Some studies have shown that inflammatory factors play an important role in nervous system diseases and fatigue. The TB500 fragment (17-13) may reduce the inflammatory response of the nervous system and improve the function of the nervous system by regulating the level of inflammatory factors[1].
Influence on the neuroendocrine system
The neuroendocrine system plays an important role in regulating the body's physiological functions and stress responses. The TB500 fragment (17-13) may regulate the activities of the nervous system by affecting the function of the neuroendocrine system. For example, it may affect the function of the hypothalamic-pituitary-adrenal axis, regulate the secretion of stress hormones such as cortisol, and thus affect the function of the nervous system.
Some studies have shown that the level of stress hormones is closely related to the feeling of fatigue and athletic performance. The TB500 fragment (17-13) may reduce the feeling of fatigue and improve athletic performance by regulating the level of stress hormones[1].
What are the effects of TB500 fragment (17-13)?
1. Tissue repair and regeneration
Wound healing of acute and chronic wounds:
For acute wounds (such as surgical incisions, burns) and chronic wounds (such as diabetic ulcers), the TB500 fragment (17-13) can reduce scar formation. Its mechanism of action may be related to promoting the orderly deposition of collagen and regulating the inflammatory response[2].
Tissue regeneration shown in animal experiments:
In animal experiments, this peptide fragment can promote the regeneration of skin, muscle, tendon, and cartilage. For example, in the skin injury model, the TB500 fragment (17-13) can stimulate the migration and proliferation of keratinocytes, accelerating wound healing (Ho E N M, 2012). For muscle and tendon injuries, it may promote tissue repair by promoting the activation and proliferation of satellite cells[3]. In the cartilage injury model, this peptide fragment may promote cartilage regeneration by regulating the metabolism and synthesis function of chondrocytes[2].
2. Anti-inflammatory properties
In chronic inflammatory diseases (such as rheumatoid arthritis, Crohn's disease), the inflammatory response persists, leading to tissue damage and organ dysfunction. As an adjuvant treatment, the TB500 fragment (17-13) can relieve disease symptoms and delay disease progression by inhibiting the inflammatory response[4].
3. Rehabilitation of musculoskeletal injuries
The TB500 fragment (17-13) accelerates the repair of muscle strains, tendonitis, and ligament injuries, shortening the rehabilitation period of athletes. In sports medicine, musculoskeletal injuries are common problems. This peptide fragment can promote the repair of damaged tissues[3].
4. Cardiac repair
After myocardial infarction, the TB500 fragment (17-13) can promote angiogenesis and the survival of cardiomyocytes, improving cardiac function. Myocardial infarction is a disease caused by the blockage of the coronary artery, leading to myocardial ischemia and hypoxia. Angiogenesis can provide oxygen and nutrients to the damaged myocardium, promoting the survival and repair of cardiomyocytes[5].
In animal models, the TB500 fragment (17-13) significantly reduces the infarct size and enhances myocardial repair. Its mechanism of action may be related to promoting the expression and release of growth factors such as vascular endothelial growth factor (VEGF).
5. Neuroprotection and brain health
The TB500 fragment (17-13) inhibits neuronal apoptosis and promotes the proliferation of neural stem cells. Neuronal apoptosis is one of the important pathological mechanisms of neurodegenerative diseases and brain injuries. This peptide fragment may inhibit neuronal apoptosis by regulating intracellular signaling pathways. At the same time, promoting the proliferation of neural stem cells can provide a new source of cells for the damaged nerve tissue, promoting nerve repair.
In stroke, traumatic brain injury (TBI), and neurodegenerative diseases (such as Alzheimer's disease), the nerve tissue is damaged to varying degrees. The TB500 fragment (17-13) may contribute to the recovery of patients through its neuroprotective and nerve repair-promoting effects[4].
6. Treatment of eye diseases
0.1% Tβ4 eye drops completely healed the wounds and relieved the symptoms in 6 patients with neurotrophic keratitis. Neurotrophic keratitis is a corneal disease caused by corneal nerve dysfunction. The TB500 fragment (17-13) may promote the healing of corneal wounds by promoting the proliferation and migration of corneal epithelial cells and regulating the inflammatory response[6].
7. Hair regeneration
The TB500 fragment (17-13) activates hair follicle stem cells and prolongs the anagen phase of hair growth. Hair follicle stem cells are the key cells for hair regeneration. They can differentiate into various cell types of the hair follicle, promoting the growth and development of hair. This peptide fragment may promote hair regeneration by regulating the proliferation and differentiation of hair follicle stem cells (Pan D Y, 2021).
Animal experiments
Mice:
The hair growth rate is accelerated. In the mouse model, the TB500 fragment (17-13) may promote the growth and development of hair by activating hair follicle stem cells[4].
Goats:
Increase the number of secondary hair follicles and promote the production of down hair. In the goat model, this peptide fragment may promote the growth of down hair by regulating the growth cycle of hair follicles and the growth rate of hair[4].
In conclusion, the TB500 fragment (17-13) can promote tissue repair, anti-inflammation, and cell regeneration, accelerate wound healing, and improve musculoskeletal function. It is of great significance for regenerative medicine, bringing new hope for the treatment of diseases such as burns and muscle injuries and the research and development of anti-inflammatory drugs, with broad application prospects.
About The Author
The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.
Scientific Journal Author
Choi B is a distinguished researcher and academic with significant affiliations to prestigious institutions like Yonsei University and Seoul National University (SNU). His work across these institutions has been instrumental in advancing various fields of study and research.
His research interests and expertise span across a wide array of subject categories. These include Microbiology, Biotechnology & Applied Microbiology, Immunology, Pharmacology & Pharmacy, and Science & Technology - Other Topics. His extensive research in these areas highlights his extensive knowledge and contributions to the scientific community. Choi B is listed in the reference of citation [2].
▎Relevant Citations
[1] Esposito S, Deventer K, Goeman J, et al. Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential[J]. Drug Testing and Analysis, 2012,4(9):733-738.DOI:10.1002/dta.1402.
[2] Choi B, Lee C, Yu J. Distinctive role of inflammation in tissue repair and regeneration[J]. Archives of Pharmacal Research, 2023,46(2):78-89.DOI:10.1007/s12272-023-01428-3.
[3] Llgen H L O, Llgen R M L O. Health and Medicine in the future: change through sports medicine. Sports Medicine in change, 2018[C]. https://www.semanticscholar.org/paper/Health-and-Medicineinthefuture%3AchangethroughL%C3%B6llgenL%C3%B6llgen/a5d6430c8b5442f02bc3238fa48ec0e657489942
[4] Pan D Y, Xu L Y, Li E M. Post-translational modification of TB4 and its functional regulation[J]. Chemistry of Life, 2021,41(04):734-740.DOI:10.13488/j.smhx.20200532.
[5] Eming S A. Evolution of immune pathways in regeneration and repair: Recent concepts and translational perspectives[J]. Seminars in Immunology, 2014,26(4):275-276.DOI:10.1016/j.smim.2014.09.001.
[6] Ho E N M, Kwok W H, Lau M Y, et al. Doping control analysis of TB-500, a synthetic version of an active region of thymosin β4, in equine urine and plasma by liquid chromatography-mass spectrometry[J]. Journal of Chromatography A, 2012,1265:57-69.DOI:10.1016/j.chroma.2012.09.043.
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