Thymosin Beta-4

Also known as: Tβ4(1–4) / Ac-SDKP; Tβ4(1–15); Tβ4(40–43) / AGES

Overview

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.

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

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.

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

Endothelial Function Preservation

Ac-SDKP enhances endothelial nitric oxide synthase (eNOS) expression, supporting nitric oxide (NO) production, which improves microvascular perfusion and capillary density.

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.

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.

Activates PI3K/Akt and ERK1/2 pathways, promoting stem cell proliferation and supporting regeneration in injured tissue environments.

Fragment 40--43 (AGES)

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

Promotion of Cardiomyocyte Survival

Enhances PI3K/Akt signaling in myocytes. Upregulates Bcl-2, downregulates Bax, mitigating apoptosis during ischemia/reperfusion injury.

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.

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

AGES fragment improves cardiac remodeling and EPDC activation in myocardial infarction models

Rhaleb NE et al. Am J Physiol Heart Circ Physiol. 2001

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

Bock-Marquette I et al. Nature. 2004

Smart N et al. Nature. 2007

Saxena A et al. Ann N Y Acad Sci. 2010