Catalpol prevents denervated muscular atrophy related to the inhibition of autophagy and reduces BAX/BCL2 ratio via mTOR pathway

Abstract

Aim

To investigate the effects of catalpol on muscular atrophy induced by sciatic nerve crush injury (SNCI).

Methods

Seventy male Kunming mice were randomized into five groups (n=10): model, sham, catalpol (Cat), rapamycin (Rapa), and catalpol+rapamycin (Rapa+Cat). The ratio of gastrocnemius muscle wet weight (right/left, R/L) between the operated leg (right) and the normal leg (left) was calculated, and acetylcholinesterase (AChE) immunohistochemistry assays were performed to observe the change of motor end plate (MEP), along with the sizes of denervated and innervated muscle fibers. The expression levels of LC3II, TUNEL, BAX/BCL-2, LC3II/LC3I and P62, Beclin1, mTOR, and p-mTOR (ser2448) proteins in muscle were examined by fluorescence immunohistochemistry or Western blotting.

Results

Results show that catalpol improved the results of the grid walking tests by reducing the percentage of foot slips, which increased the gastrocnemius muscle wet weight (R/L), enhanced AChE expression at the MEP, and enlarged the section area of the muscle. The expression of LC3II and TUNEL was significantly inhibited by catalpol. The BAX/BCL-2 ratio was significantly increased in muscles of denervated and control groups. Lower LC3II/LC3I and BAX/BCL-2 ratios in denervated muscles were also detected after catalpol treatment.

Conclusion

These results indicated that apoptosis and autophagy play a role in the regulation of denervation-induced muscle atrophy after SNCI, and catalpol alleviates muscle atrophy through the regulation of muscle apoptosis and autophagy via the mTOR signaling pathway.

Keywords:

• catalpol
• sciatic nerve crush injury
• SNCI
• denervated muscle atrophy
• autophagy
• muscle apoptosis

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81073084), the Natural Science Foundation Project of CQ (cstc2018jcyjAX0158), Fundamental Research Funds to graduating students for the Central Universities (XDJK2017D154), and Southwest University Undergraduate Science and Technology Innovation Fund (Project No 20162902001 & YX2017-CXZD-02).

Author contributions

All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.