Targeting Autophagy with Geniposide Ameliorates Atherosclerosis in ApoE−∕− Mice.

Yang, Xiaodan; Shi, Jiaxi; He, Weifeng; Li, Junlong; Li, Rui; Pi, Jianbin; Luo, Yuan; Gu, Mingyang; Wang, Xiaolong; Wu, Wei; Qing, Lijin

Atherosclerosis (AS) is a major cause of mortality worldwide. Geniposide (GP) has lipolytic and anti-inflammatory effects and is widely administered for the treatment of cardiovascular disease. There is considerable evidence for the importance of autophagy in the cardiovascular system, and GP can promote autophagy and improve AS. However, the underlying mechanism is still unclear; network pharmacology and molecular docking suggest that GP may play anti-atherosclerotic roles by regulating the PI3K/Akt/mTOR pathway, which is a typical autophagy signal transduction approach. We further hypothesized that GP ameliorates AS by regulating autophagy through the PI3K/Akt/mTOR pathway. Oil Red O, Sirius Red, and Masson's trichrome staining revealed that GP can inhibit atherosclerotic lipid accumulation and stabilize plaques. Macrophages absorb lipids, form foam cells, and destabilize plaques. Immunohistochemical staining revealed that GP reduces the expression of F4/80, a major macrophage marker. We used western blotting (WB) and immunofluorescence (IF) to measure the protein levels of PI3K/Akt/mTOR, sequestosome-1, Beclin1, and long-chain base 3 (LC3). The experimental results revealed that GP can increase the expression of LC3, increase the expression of Beclin1, and decrease P62. Additionally, it inhibits the phosphorylation of PI3K/Akt/mTOR. In conclusion, GP can effectively treat AS by enhancing autophagy through the PI3K/Akt/mTOR pathway.

ATHEROSCLEROSIS prevention; CHINESE medicine; PROTEINS; HDL cholesterol; COMPUTER-assisted molecular modeling; BIOLOGICAL models; AUTOPHAGY; PROTEIN kinases; RESEARCH funding; CARRIER proteins; PHOSPHORYLATION; DATA analysis; HYPERLIPIDEMIA; HERBAL medicine; LIPIDS; ENZYME-linked immunosorbent assay; PHARMACEUTICAL chemistry; ELECTRON microscopy; CELLULAR signal transduction; FLUORESCENT antibody technique; DESCRIPTIVE statistics; LDL cholesterol; ATHEROSCLEROSIS; EXPERIMENTAL design; MICE; IMMUNOHISTOCHEMISTRY; GENE expression; GLYCOSIDES; ANIMAL experimentation; WESTERN immunoblotting; CHOLESTEROL; ANALYSIS of variance; STATISTICS; PHOSPHOTRANSFERASES; TRANSFERASES; STAINS & staining (Microscopy); TRIGLYCERIDES; DATA analysis software; COMPARATIVE studies; CARDIOVASCULAR agents; BIOMARKERS; SIGNAL peptides; PHARMACODYNAMICS

American Journal of Chinese Medicine, 2024, Vol 52, Issue 8, p2469

0192-415X

Academic Journal

10.1142/S0192415X24500940