Ampelopsin attenuates brain aging of D-gal-induced rats through miR-34a-mediated SIRT1/mTOR signal pathway

Abstract

// Xianjuan Kou 1,* , Xingran Liu 2,* , Xianbing Chen 3 , Jie Li 2 , Xiaoqi Yang 2 , Jingjing Fan 1 , Yi Yang 1 and Ning Chen 1 1 Hubei Key Laboratory of Sport Training and Monitoring, College of Health Science, Wuhan Sports University, Wuhan, China 2 Graduate School, Wuhan Sports University, Wuhan, China 3 College of Medicine, Hubei University for Nationalities, Enshi, China * These authors have contributed equally to this work Correspondence to: Ning Chen, email: // Keywords : ampelopsin, aging, autophagy, miR-34a, SIRT1-mTOR signal pathway, Gerotarget Received : July 15, 2016 Accepted : October 17, 2016 Published : October 21, 2016 Abstract The underlying molecular mechanisms for aging-related neurodegenerative diseases such as Alzheimer’s disease (AD) are not fully understood. Currently, growing evidences have revealed that microRNAs (miRNAs) are involved in aging and aging-related diseases. The up-regulation of miR-34a has been reported to be associated with aging-related diseases, and thus it should be a promising therapeutic target. Ampelopsin, also called dihydromyricetin (DHM), a natural flavonoid from Chinese herb Ampelopsis grossedentata , has been reported to possess multiple pharmacological functions including anti-inflammatory, anti-oxidative and anti-cancer functions. Meanwhile, it has also gained tremendous attention against neurodegenerative diseases as an anti-aging compound. In the present study, the model rats with D-gal-induced brain aging revealed an obvious expression of miR-34a; in contrast, it could be significantly suppressed upon DHM treatment. In addition, target genes associated with miR-34a in the presence of DHM treatment were also explored. DHM supplementation inhibited D-gal-induced apoptosis and rescued impaired autophagy of neurons in hippocampus tissue. Moreover, DHM activated autophagy through up-regulated SIRT1 and down-regulated mTOR signal pathways due to the down-regulated miR-34a. In conclusion, DHM can execute the prevention and treatment of D-gal-induced brain aging by miR-34a-mediated SIRT1-mTOR signal pathway.