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ZhiShiXiaoPi Tang (ZSXPT) is a Chinese traditional medicine formula that contains 10 Chinese traditional medicine substances. It has been widely used to treat patients with functional dyspepsia (FD). However, the protective effect of ZSXPT and its molecular mechanisms in FD still remain elusive. To investigate the protective effect of ZSXPT on autophagy induced by Corticosterone (Cort) in PC12 cells which have typical neuron characteristics and have been widely used as a model system for depression studies and FD rats, and explore its underlying mechanisms. In this study, high-performance liquid chromatography fingerprint analysis was performed to characterize the chemical composition of ZSXPT. Depression-induced autophagy, ROS generation, and changes in mitochondrial membrane potential (MMP) were investigated in Cort-induced PC12 cells and in FD rats to evaluate the protective effects of ZSXPT. Our results show that ZSXPT treatment protects neurons against Cort-induced damage and apoptosis by increasing cell viability and reducing the release of lactate dehydrogenase. ZSXPT decreased Cort-induced ROS generation, increased MMP, and accelerated autophagy through the blockade of the mammalian target of rapamycin (mTOR) pathway. Moreover, we observed similar findings when we studied ZSXPT in a rat model of FD. Our in vitro and in vivo results indicate that the neuroprotective effect of ZSXPT against autophagy-induced damage and apoptosis occurs mainly by blocking the mTOR pathway in Cort-induced PC12 cells and in FD rats. Taken together, these data provide reliable experimental evidence and explain the molecular mechanism by which ZSXPT ameliorates FD. Image 1 [ABSTRACT FROM AUTHOR]