Effects of ginkgo flavone aglycone on atherosclerosis based on network pharmacology,molecular docking,and in vitro experiments  

作　　者：Miao Zhou Rui Li Qin Li Yan-Li Huang Shi-Jing Liu Ji-Yu Chen Yan He 

机构地区：[1]Animal Core Facility,Nanjing Medical University,Nanjing 211166,China [2]The Animal Experimental Center,China Pharmaceutical University,Nanjing 211166,China [3]Clinical Trials Center,The Affiliated Hospital of Guizhou Medical University,Guiyang 550000,China [4]Key Laboratory of Basic Pharmacology of Ministry of Education,Zunyi Medical University,Zunyi 563000,China [5]Office of Academic Research,The Affiliated Hospital of Guizhou Medical University,Guiyang 550000,China

出　　处：《TMR Modern Herbal Medicine》2024年第2期1-10,共10页TMR现代中药

基　　金：supported by the Science and Technology Foundation of Basic Research Program of Guizhou Province([2023]General 371,[2020]1Y381);the Administration of Traditional Chinese Medicine of Guizhou Province(QZYY-2018-130);the project of Key Laboratory of Basic Pharmacology of Ministry of Education,Zunyi Medicial University(No.qianjiaoheKYzi[2022]395);the Cultivation Plan of the NSFC(National Natural Science Foundation of China)of the affiliated hospital of Guizhou Medical University(GYFYNSFC-2021-55,GYFYNSFC-2021-56);the Cultivation Plan of the NSFC(National Natural Science Foundation of China)of Guizhou Medical University(21NSFCP13);the Science and Technology Foundation of Health Commission of Guizhou Province(gzwkj 2022-221).

摘　　要：Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for the treatment of AS remain unclear.Methods:To evaluate and identify the potential pharmacological mechanisms of GA in AS treatment,the program Cytoscape was used to generate network mappings of the GA-AS-potential target gene.GO and KEGG enrichment analyses were performed to further investigate the potential mechanism of AS and the pharmacological properties of GA.A molecular docking approach was utilized to determine the GA components that interact with Akt.In vitro experiments were carried out to identify the anti-atherosclerotic effects of GA by targeting Akt.Results:Network pharmacological research determined that the active components of GA(quercetin,kaempferol,and isorhamnetin)correlated with AS target genes such as AKT1,EGFR,SRC,ESR1,PTGS2,MMP9,KDR,GSK3B,APP,and MMP2,respectively.GO enrichment and KEGG analysis showed that PI3K-Akt signaling may play an important role in GA treatment.Molecular docking experiments indicated that quercetin,kaempferol,and isorhamnetin integrate into the binding pockets of the most potentially beneficial GA-AS target protein(Akt).Consequently,cell experiments were conducted to support the anti-atherosclerotic activity of GA on AS by inhibiting the phosphorylation of AKT1 and its downstream signaling molecules,which regulated the proliferation of HASMCs.Conclusion:Our results detailed GA's active ingredients,potential targets,and molecular basis against AS.GA may exert anti-atherosclerotic effects by suppressing Akt phosphorylation and inhibiting the proliferation of HASMCs.It also proposed a viable approach to determining the scientific foundation and therapeutic mechanism of Chinese herbal medicine extracts in disease therapy.

关 键 词：network pharmacology ginkgo flavone aglycones ATHEROSCLEROSIS molecular docking KAEMPFEROL QUERCETIN ISORHAMNETIN 

分 类 号：R285[医药卫生—中药学]