PMID- 30972164 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1943-8141 (Print) IS - 1943-8141 (Electronic) IS - 1943-8141 (Linking) VI - 11 IP - 3 DP - 2019 TI - Catalpol improves axonal outgrowth and reinnervation of injured sciatic nerve by activating Akt/mTOR pathway and regulating BDNF and PTEN expression. PG - 1311-1326 AB - Aim: This study aimed to investigate the effects of catalpol on sciatic nerve crush injury (SNCI) and further explore the role of Akt/mTOR pathway in its pharmacological efficacy. Methods: Mice with SNCI in the right were treated with catalpol. Rapamycin was used to block mTOR signal activation. After sciatic motor nerve function was observed, the gastrocnemius muscles, injury sciatic nerve and spinal cord L4-L6 were isolated. TUNEL staining was done to assess the neuronal apoptosis; Transmission electron microscopy (TEM) was performed to observe the microstructure of regenerated myelinated nerve fibers. The expression of proteins in Akt/mTOR pathway, those related to axon regeneration and cell apoptosis was detected by Western blotting. Brain derived neurotrophic factor (BDNF), phosphatase and tensin homolog deleted on chromosome ten (PTEN), growth associated protein-43 (GAP-43), pro- and anti-apoptosis protein including Bax and BCL-2. Results: Catalpol significantly improved the function of injured sciatic motor nerve and facilitated the sciatic motor and sensory nerve fiber growth and the reinnervation of gastrocnemius muscles. TEM showed catalpol increased the density and thickness of regenerated myelinated nerve fibers, which exhibited a regular arrangement. Catalpol significantly reduced the number of apoptotic cells and increased the Bcl-2/Bax ratio in the L4-L6 spinal cord anterior horn. Importantly, catalpol significantly increased the expression of p-Akt, p-mTOR, p-p70S6K, GAP-43 and BDNF, but decreased PTEN expression. Blockade of mTOR activation was partially abrogated by catalpol. Conclusion: Catalpol may improve SCNI by enhancing the axonal growth via activating the Akt/mTOR pathway and modulating BDNF and PTEN expression. FAU - Zhu, Huifeng AU - Zhu H AD - College of Pharmaceutical Sciences and Traditional Chinese Medicine, Southwest University Chongqing 400715, China. AD - Engineering Research Center for Chongqing Pharmaceutical Process and Quality Control Chongqing 400715, China. FAU - Wang, Yuan AU - Wang Y AD - College of Pharmaceutical Sciences and Traditional Chinese Medicine, Southwest University Chongqing 400715, China. AD - Engineering Research Center for Chongqing Pharmaceutical Process and Quality Control Chongqing 400715, China. FAU - Yang, Xian AU - Yang X AD - Department of Pharmacy, The Seventh People's Hospital of Chengdu Chengdu 610041, China. FAU - Wan, Guoran AU - Wan G AD - Class 7 Grade 1, Chongqing Three Gorges Medical College Chongqing 400016, China. FAU - Qiu, Yan AU - Qiu Y AD - College of Pharmaceutical Sciences and Traditional Chinese Medicine, Southwest University Chongqing 400715, China. AD - Engineering Research Center for Chongqing Pharmaceutical Process and Quality Control Chongqing 400715, China. FAU - Ye, Xiyue AU - Ye X AD - College of Pharmaceutical Sciences and Traditional Chinese Medicine, Southwest University Chongqing 400715, China. AD - Engineering Research Center for Chongqing Pharmaceutical Process and Quality Control Chongqing 400715, China. FAU - Gao, Yuqing AU - Gao Y AD - College of Pharmaceutical Sciences and Traditional Chinese Medicine, Southwest University Chongqing 400715, China. AD - Engineering Research Center for Chongqing Pharmaceutical Process and Quality Control Chongqing 400715, China. FAU - Wan, Dong AU - Wan D AD - Department of Emergency and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China. LA - eng PT - Journal Article DEP - 20190315 PL - United States TA - Am J Transl Res JT - American journal of translational research JID - 101493030 PMC - PMC6456559 OTO - NOTNLM OT - Akt/mTOR pathway OT - Catalpol OT - axon regeneration OT - sciatic nerve crush injury COIS- None. EDAT- 2019/04/12 06:00 MHDA- 2019/04/12 06:01 PMCR- 2019/03/15 CRDT- 2019/04/12 06:00 PHST- 2018/09/19 00:00 [received] PHST- 2019/01/09 00:00 [accepted] PHST- 2019/04/12 06:00 [entrez] PHST- 2019/04/12 06:00 [pubmed] PHST- 2019/04/12 06:01 [medline] PHST- 2019/03/15 00:00 [pmc-release] PST - epublish SO - Am J Transl Res. 2019 Mar 15;11(3):1311-1326. eCollection 2019.