Study On The Mechanism Of Mountain-cultivated Ginseng And Cultivated Ginseng In The Treatment Of Cardiovascular Diseases

Objective: Ginseng as a kind of precious Chinese herbal medicine,has been widely studied on its pharmacological effects and clinical efficacy in recent years.Pharmacological studies have shown that Ginseng on cardiovascular system,digestive system,immune system and central nervous system has certain pharmacological action,clinical mainly used in treatment of cardiovascular disease(CVD),diabetes,neurasthenia and other symptoms.Ginseng can be divided into Mountain-cultivated Ginseng,Transplant Wild Ginseng and Cultivated Ginseng.In this paper,Mountain-cultivated Ginseng and Cultivated Ginseng in Huanren area of Liaoning Province were studied,the secondary metabolites were analyzed by UPLC-Q-TOF-MS,the network pharmacology technique was used to study the targets and pathways of CVD treatment by the different metabolites,zebrafish model animals were used to verify the selected targets and pathways,and to study the differences of the mechanism between Mountain-cultivated Ginseng and Cultivated Ginseng in treating CVD.Method:(1)We analyzed and screened the differences of secondary metabolites between the 20-year-old Mountain-cultivated Ginseng and the 4-year-old Cultivated Ginseng based on UPLC-Q-TOF-MS.(2)We constructed the “differentially components-targets” network of 11 differential metabolites based on network pharmacology,and analyze to study the differences of targets and pathways in CVD of Mountain-cultivated Ginseng and Cultivated Ginseng.(3)The vascular injury model of zebrafish was established to study the effects of Mountain-cultivated Ginseng and Cultivated Ginseng on angiogenesis and protection of injured vessels.The expression levels of related proteins were analyzed by RT-q PCR and Western Blot.The effects of Ginsenoside Re and Ginsenoside C on angiogenesis and protection of injured blood vessels were also studied.Result:(1)A total of 11 differential metabolites were screened out according to the VIP value of Mountain-cultivated Ginseng and Cultivated Ginseng,respectively:1-Palmitoyl Lysophosphatidic Acid,Ginsenoside Rg3,Ginsenoside Re,Ginsenoside B2,Ginsenoside F5,Ginsenoside C,Citric acid,N2-Acetyl-L-ornithine,Notoginsenoside Fa,L-Phenylalanine,Ginsenoside M7 cd.(2)Network pharmacology results screened 11 different compositions for 234 targets and CVD related targets for 4382,“differentially components-targets" network and protein interaction(PPI)network were constructed,a total of 44 key targets for treatment of CVD mainly occurred in PI3K-Akt signaling pathways,TNF signaling pathways,the NF-kappa B signaling pathways,T cell receptor signal transduction pathway.(3)Mountain-cultivated Ginseng and Cultivated Ginseng can promote the angiogenesis of subintestinal vein and protect the injured internode vessels in zebrafish.Both of them up-regulated the expression of VEGFR2 and HIF-1α,and inhibited the expression of IL-6 and TNF-α.The effect of Mountain-cultivated Ginseng had a significant difference with Cultivated Ginseng.Ginsenoside Re and Ginsenoside C also had the effect of promoting subintestinal vein angiogenesis and protecting injured internode vessels in zebrafish.Conclusion: This study firstly screened the targets and pathways of Mountain-cultivated Ginseng and Cultivated Ginseng in the treatment of CVD based on UPLC-Q-TOF-MS and network pharmacology.Molecular docking technology was used to verify the docking of key targets and differential components,and zebrafish model was used to study the promoting angiogenesis and protecting damaged blood vessels of two kinds of Ginsengs.In this study,the secondary metabolites of Mountain-cultivated Ginseng and Cultivated Ginseng were studied to analyze the differences of their mechanism on CVD,so as to provide some theoretical basis for clinical application of Ginseng in the treatment of CVD.