Phytomedicine : international journal of phytotherapy and phytopharmacology · 2022
Biflavonoids from Ginkgo biloba leaves as a novel anti-atherosclerotic candidate: Inhibition potency and mechanistic analysis.
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Wang Li-Tao, Huang Han, Chang Yuan-Hang, Wang Yan-Qiu, Wang Jian-Dong, Cai Zi-Hui, Efferth Thomas, Fu Yu-Jie
Аннотация
BACKGROUND: Ginkgo biloba L. is one of the oldest trees on earth, and its leaves have been used since ages as herbal medicine to treat cerebrovascular disorders. It is worth noting that in addition to the widely concerned flavonoids and terpenoids, it also contains various thus far neglected biflavonoids. In fact, biflavonoids are flavonoids consisting of apigenin or its derivatives as monomeric scaffold, and are linked via C-C or C-O-C bond.
PURPOSE: Based on the structural similarity of flavonoids, we hypothesized that biflavonoids may play a potential role in the treatment of cerebrovascular diseases. Here, we describe the effectiveness and underlying mechanisms for prevention and treatment of atherosclerosis (AS) by biflavonoids.
STUDY DESIGN AND METHODS: Four main biflavonoids in Ginkgo biloba leaves were screened by oleic acid-induced lipid production in HepG2 cells. The non-covalent effects of biflavonoids on the potential targets of atherosclerosis were screened by reverse targeting and molecular dynamics simulation. The interactions between biflavonoids and potential targets were evaluated by an exogenous cell model, which verified the consistency of the simulation results.
CONCLUSION: Among all four biflavonoids, ginkgetin significantly inhibited oleic acid-induced lipid production in HepG2 cells and reduced total cholesterol and triglyceride levels. The interaction of ginkgetin with CDK2 through π-alkyl and hydrogen bonds increased the binding of molecules and proteins. Ginkgetin arrested the cells in the G1-S phase, which significantly inhibited abnormal cell growth which closely related to the occurrence and development of atherosclerosis. Biflavonoids could be a promising natural medicine for the treatment of atherosclerosis.
PURPOSE: Based on the structural similarity of flavonoids, we hypothesized that biflavonoids may play a potential role in the treatment of cerebrovascular diseases. Here, we describe the effectiveness and underlying mechanisms for prevention and treatment of atherosclerosis (AS) by biflavonoids.
STUDY DESIGN AND METHODS: Four main biflavonoids in Ginkgo biloba leaves were screened by oleic acid-induced lipid production in HepG2 cells. The non-covalent effects of biflavonoids on the potential targets of atherosclerosis were screened by reverse targeting and molecular dynamics simulation. The interactions between biflavonoids and potential targets were evaluated by an exogenous cell model, which verified the consistency of the simulation results.
CONCLUSION: Among all four biflavonoids, ginkgetin significantly inhibited oleic acid-induced lipid production in HepG2 cells and reduced total cholesterol and triglyceride levels. The interaction of ginkgetin with CDK2 through π-alkyl and hydrogen bonds increased the binding of molecules and proteins. Ginkgetin arrested the cells in the G1-S phase, which significantly inhibited abnormal cell growth which closely related to the occurrence and development of atherosclerosis. Biflavonoids could be a promising natural medicine for the treatment of atherosclerosis.