Tβ4 is a 43-amino acid peptide involved in actin regulation, wound healing, and tissue repair. Its active fragments (1–4, 1–15, 40–43) target fibrosis, oxidative stress, and organ-specific regeneration, especially in cardiac and fibrotic diseases.
Thymosin Beta-4
Also known as: Tβ4(1–4) / Ac-SDKP; Tβ4(1–15); Tβ4(40–43) / AGES
Overview
Benefits
- Reduces fibrosis and inflammation
- Protects cardiac tissue
- Prevents oxidative damage
- Improves vascular and mitochondrial function
- Promotes tissue regeneration
Consider This Peptide If You Want To
- Reduce fibrosis, inflammation, or oxidative damage
- Recover from organ or tissue injury
Dosage & Administration
Dosage Guidelines
Recommended Dosage
• Amount:300 mcg
• Frequency:daily
• Duration:2 weeks
• Rest Period:6 weeks
• Time of Day:morning
• Ingestion:subcutaneous
Do not co-administer with full-length Tβ4; use specific fragments based on therapeutic target
Administration Routes:OralSubcutaneous
Research Findings on Dosage:
Oral Administration (Fragments 1--4 & 1--15):
• Commonly Reported Dosage: 500 mcg per capsule, taken twice daily
• Duration: 4-12 weeks, depending on individual goals
Subcutaneous Injection (Fragments 1--15 & 40--43):
• Commonly Reported Dosage: 300 mcg to 1 g daily or 2.5 mg every other day (1--15); 100--500 mcg per injection (40--43)
• Duration: 2--4 week cycles for 40--43; up to 3 months for 1--15 followed by a 6-week break
Administration Notes:
• Do not co-administer with full-length Tβ4 simultaneously due to receptor competition
• Commonly stacked with BPC-157, Epitalon, or mitochondrial peptides for synergistic tissue repair
• Demonstrates oral bioavailability in animal models (Ac-SDKP)
Mechanism of Action
Mechanism of Action
How this peptide works in the body
Fragment 1--4 (Ac-SDKP)
Suppression of TGF-β1 Signaling and Fibrosis
Ac-SDKP binds to and inhibits the TGF-β1 receptor complex, reducing downstream phosphorylation of SMAD2 and SMAD3. This decreases transcription of pro-fibrotic genes (e.g., COL1A1, fibronectin, α-SMA), limiting myofibroblast activation and extracellular matrix deposition.
NF-κB Inhibition and Cytokine Suppression
By preventing IκB degradation, Ac-SDKP reduces NF-κB nuclear translocation. This downregulates expression of inflammatory cytokines like TNF-α, IL-1β, and IL-6, lowering inflammation in fibrotic tissues.
Immune Cell Modulation
The peptide decreases monocyte/macrophage infiltration via downregulation of MCP-1 and adhesion molecules (VCAM-1, ICAM-1), reducing immune-mediated tissue injury.
Endothelial Function Preservation
Ac-SDKP enhances endothelial nitric oxide synthase (eNOS) expression, supporting nitric oxide (NO) production, which improves microvascular perfusion and capillary density.
Fragment 1--15
Inhibition of Intrinsic Apoptosis Pathways
Tβ4(1--15) modulates mitochondrial integrity by increasing Bcl-2 expression and reducing Bax, preventing mitochondrial outer membrane permeabilization and cytochrome c release. This reduces caspase-9 and caspase-3 activation.
Antioxidant Defense Enhancement
Stimulates expression of antioxidant enzymes: superoxide dismutase (SOD), catalase, and glutathione peroxidase. Also boosts intracellular GSH:GSSG ratio to neutralize ROS.
Cytoskeletal and Membrane Stabilization
Preserves actin dynamics, stabilizes focal adhesions, and reduces lipid peroxidation during oxidative stress, supporting tissue integrity during repair.
Cell Survival and Regenerative Signaling
Activates PI3K/Akt and ERK1/2 pathways, promoting stem cell proliferation and supporting regeneration in injured tissue environments.
Fragment 40--43 (AGES)
Anti-Fibrotic Remodeling in Myocardium
Attenuates TGF-β1-mediated fibroblast-to-myofibroblast transition. Reduces collagen I synthesis and α-SMA expression, limiting scar formation after ischemic injury.
Matrix Metalloproteinase Modulation
Inhibits MMP-2/9 overactivity and maintains TIMP-1 equilibrium, reducing pathological ECM remodeling and preserving cardiac structure.
Promotion of Cardiomyocyte Survival
Enhances PI3K/Akt signaling in myocytes. Upregulates Bcl-2, downregulates Bax, mitigating apoptosis during ischemia/reperfusion injury.
Reduction of Pro-Inflammatory Cytokines
Suppresses TNF-α and IL-6 production in infarct border zones. Supports anti-inflammatory cytokine balance and post-MI tissue healing.
Activation of Epicardial-Derived Progenitor Cells
Stimulates integrin-linked kinase (ILK) and focal adhesion kinase (FAK), recruiting EPDCs for neovascularization and cardiac regeneration.
Consider Stacking With
- BPC-157
- Epitalon
- Thymosin Alpha-1
- MOTS-c
- SS-31
- FOXO4-DRI
Side Effects & Cautions
Common Side Effects
- Mild redness or irritation
Cautions
- Avoid in active cancer
- Avoid co-use with full-length Tβ4
- Caution in mast cell disorders
Rare Side Effects
- Allergic reactions (rare)
Research & References
Research Highlights
Ac-SDKP demonstrated significant reduction in organ fibrosis in multiple preclinical models
Tβ4(1--15) shown to protect cardiac fibroblasts under oxidative stress and promote antioxidant gene expression
AGES fragment improves cardiac remodeling and EPDC activation in myocardial infarction models
References
Rhaleb NE et al. Am J Physiol Heart Circ Physiol. 2001
Kumar S, Gupta S. PLOS ONE. 2011
Yang F et al. Hypertension. 2004
Pokharel S et al. Cardiovasc Res. 2003
Bock-Marquette I et al. Nature. 2004
Smart N et al. Nature. 2007
Saxena A et al. Ann N Y Acad Sci. 2010