Drug Design, Development and Therapy (Dec 2018)
Catalpol prevents denervated muscular atrophy related to the inhibition of autophagy and reduces BAX/BCL2 ratio via mTOR pathway
Abstract
Yuan Wang,1,* Yali Shao,1 Yuqing Gao,1 Guoran Wan,2 Dong Wan,3,* Huifeng Zhu,1 Yan Qiu,1 Xiyue Ye1 1Department of Chinese Medicine, College of Pharmaceutical Sciences and Traditional Chinese Medicine, Southwest University, Chongqing Engineering Research Center for Pharmacological Evaluation, Chongqing 400715, China; 2Department of Clinic Medicine, Chongqing Three Gorges Medical College, Chongqing 404120, China; 3Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China *These authors contributed equally to this work 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
