Ginsenoside Rgl regulates autophagy through AMPK/mTOR signaling pathway and delays brain aging in mice / 中国药理学通报

ABSTRACT

Aim To investigate the mechanism by which ginsenoside Rgl regulates autophagy anrl delays brain aging in mice through AMPK/mTOR signaling pathway.Methods C57BL/6J male mice were ran¬domly divided into four groups, namely brain aging model group ,control group, Rgl anti-aging group,auto¬phagy activator Rapamycin anti-aging group.After the modeling was completed, the test of each experimental index would be carried out on the next day.Morris wa¬ter maze experiment was used to detect the learning and memory ability of mice.Paraffin sections of the hippocampus were prepared, HE , Nissl and immunohis- tochemical staining were used to observe the morpholo¬gy of hippocampal neurons, the number of neurons and Nissl bodies was counted, and autophagy-related proteins p62 , ATG5 , ULK1 were detected.Brain tissue homogenates were prepared to detect the aetivity of brain tissue acetylcholinesterase ( AChE ).Western blot was userl to detect brain tissue autophagy-related proteins LC3II, P62, beclinl, P-AMPK/AMPK, P- mTOR/mTOR and apoptosis protein P53.Results Water maze test showed that Rgl and Hap significantly improved the learning and memory abilities of brain-ag¬ing mice.HE and Nissl staining showed that Rgl and Rap decreased necrotic cells and increased the number of Nissl bodies in the hippocampus of brain-aging mice.Immunohistochemistry staining showed that Rgl and Rap decreased the expression of neuronal autoph- agv protein P62 in hippocampus and increased the ex-pression of ATG5 and ULK1.Rgl and Rap decreased the activity of AhcE in brain-aging mice.Western blot showed that Rgl and Rap increased autophagy-related proteins LC3II, Beclinl , P-AMPK/AMPK, but de¬creased the expression of P-mTOR/mTOR, P62, P53.Conclusions Ginsenoside Rgl can effectively antago¬nize the aging effect of D-gal on mouse brain.The pos¬sible mechanism is related to the regulation of autoph- agv by Rgl through AMPK/mTOR signaling pathway.