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Purpose <p>This study investigated the therapeutic potential of combining aerobic exercise and celastrol treatment in promoting tendon healing and functional recovery following Achilles tendon injuries in rats.</p> Method <p>Rats with suture-repaired tendons were divided into sham surgery, aerobic exercise, celastrol treatment, and exercise/celastrol, and untreated groups. The Achilles Functional Index (AFI) scores were recorded over 4 weeks to assess motor function. Enzyme-Linked Immunosorbent Assay (ELISA) analysis was performed to measure anti-inflammatory cytokine (IL-4, IL-10, TGF-β) levels. Flow cytometry was used to evaluate the balance of M1 and M2 macrophages. Tensile tests were conducted to assess mechanical strength, and histological analyses using H&amp;E staining were performed to evaluate tendon healing.</p> Results <p>The aerobic exercise, celastrol treatment, and exercise/celastrol combination groups showed significant improvements in AFI scores compared to the untreated group. ELISA analysis revealed higher levels of anti-inflammatory cytokines in the treated groups, with the exercise/celastrol combination group showing the most significant increase. Flow cytometry analysis demonstrated a shift toward a pro-healing phenotype in the exercise/celastrol group. Tensile tests indicated improved mechanical strength in the exercise/celastrol group. Histological studies showed enhanced tendon healing and collagen fiber alignment in the exercise/celastrol group.</p> Conclusion <p>The combination of aerobic exercise and celastrol therapy effectively promoted tendon healing and functional recovery in rats with Achilles tendon injuries. The synergistic effects of the treatments were evident in improved motor function, modulation of inflammatory response, macrophage polarization, mechanical strength, and histological outcomes. This study highlights the potential of combining aerobic exercise and celastrol as a promising therapeutic strategy for enhancing tendon repair.</p> Lay Summary <p>This study investigated the effectiveness of combining aerobic exercise and celastrol treatment in healing Achilles tendon injuries in rats. Rats with repaired tendons were divided into four groups: exercise, celastrol, combined, and untreated. The combined treatment group showed the most significant improvements in motor function, reduced inflammation, and enhanced tendon healing compared to the other groups. These findings suggest that combining aerobic exercise and celastrol therapy may be a promising approach for accelerating tendon repair and recovery.</p>

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The Effect of Celastrol with Four Weeks of Aerobic Exercise on Tendon Regeneration in the Male Wistar Rats

  • 期刊论文

  • 发表日期：

    2026年2月26日

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  • Arash Bagherzadeh,
  • Yaser Kazemzadeh,
  • Arash Abdolmaleki,
  • Zohreh Afsharmand

摘要

Purpose

This study investigated the therapeutic potential of combining aerobic exercise and celastrol treatment in promoting tendon healing and functional recovery following Achilles tendon injuries in rats.

Method

Rats with suture-repaired tendons were divided into sham surgery, aerobic exercise, celastrol treatment, and exercise/celastrol, and untreated groups. The Achilles Functional Index (AFI) scores were recorded over 4 weeks to assess motor function. Enzyme-Linked Immunosorbent Assay (ELISA) analysis was performed to measure anti-inflammatory cytokine (IL-4, IL-10, TGF-β) levels. Flow cytometry was used to evaluate the balance of M1 and M2 macrophages. Tensile tests were conducted to assess mechanical strength, and histological analyses using H&E staining were performed to evaluate tendon healing.

Results

The aerobic exercise, celastrol treatment, and exercise/celastrol combination groups showed significant improvements in AFI scores compared to the untreated group. ELISA analysis revealed higher levels of anti-inflammatory cytokines in the treated groups, with the exercise/celastrol combination group showing the most significant increase. Flow cytometry analysis demonstrated a shift toward a pro-healing phenotype in the exercise/celastrol group. Tensile tests indicated improved mechanical strength in the exercise/celastrol group. Histological studies showed enhanced tendon healing and collagen fiber alignment in the exercise/celastrol group.

Conclusion

The combination of aerobic exercise and celastrol therapy effectively promoted tendon healing and functional recovery in rats with Achilles tendon injuries. The synergistic effects of the treatments were evident in improved motor function, modulation of inflammatory response, macrophage polarization, mechanical strength, and histological outcomes. This study highlights the potential of combining aerobic exercise and celastrol as a promising therapeutic strategy for enhancing tendon repair.

Lay Summary

This study investigated the effectiveness of combining aerobic exercise and celastrol treatment in healing Achilles tendon injuries in rats. Rats with repaired tendons were divided into four groups: exercise, celastrol, combined, and untreated. The combined treatment group showed the most significant improvements in motor function, reduced inflammation, and enhanced tendon healing compared to the other groups. These findings suggest that combining aerobic exercise and celastrol therapy may be a promising approach for accelerating tendon repair and recovery.