PMID- 36120313 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220920 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - Investigation of the pharmacological effect and mechanism of mountain-cultivated ginseng and garden ginseng in cardiovascular diseases based on network pharmacology and zebrafish experiments. PG - 920979 LID - 10.3389/fphar.2022.920979 [doi] LID - 920979 AB - Ginseng (Panax ginseng C.A. Mey) is a kind of perennial herb of the Panax genus in the Araliaceae family. The secondary metabolites of mountain-cultivated ginseng (MCG) and garden ginseng (GG) vary greatly due to their different growth environments. To date, the differences in their pharmacological effects on cardiovascular diseases (CVDs) and their clinical applications remain unclear. To distinguish between the components of MCG and GG, ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was performed. Next, the relationship between the expression of metabolites and the categories of the sample were analyzed using supervised partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis. A network-based pharmacology approach was developed and applied to determine the underlying mechanism of different metabolites in CVD. In the present study, the role of MCG and GG in angiogenesis and their protective effects on damaged blood vessels in a vascular injury model of zebrafish were investigated. Using UPLC-Q-TOF/MS, 11 different metabolites between MCG and GG were identified. In addition, 149 common target genes associated with the metabolites and CVD were obtained; these targets were related to tumor protein P53, proto-oncogene tyrosine-protein kinase Src, human ubiquitin-52 amino acid fusion protein, ubiquitin-40S ribosomal protein S27a, polyubiquitin B, signal transducer and activator of transcription 3, isocitrate dehydrogenase 1, vascular endothelial growth factor A, glycose synthase kinase-3B, and coagulation factor II and were associated with the regulation of the phosphoinositide 3-kinase-Akt signaling pathway, the tumor necrosis factor signaling pathway, and the hypoxia-inducible factor-1 (HIF-1) signaling pathway, which play important roles in the curative effect in CVD treatment. Both types of ginseng can promote the growth of the subintestinal vessel plexus and protect injured intersegmental vessels through the HIF-1alpha/vascular endothelial growth factor signaling pathway in a dose-dependent manner. In addition, MCG has a stronger impact than GG. This is the first time metabolomics and network pharmacology methods were combined to study the difference between MCG and GG on CVDs, which provides a significant theoretical basis for the clinical treatment of CVD with two kinds of ginseng. CI - Copyright (c) 2022 Yu, Zhang, Liu, Chen, Wang, Zhu and Gao. FAU - Yu, Ting AU - Yu T AD - Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Zhang, Yan-Xin AU - Zhang YX AD - SPH XingLing Sci&Tech. Pharmaceutical Co., Ltd., Shanghai, China. FAU - Liu, Xin-Juan AU - Liu XJ AD - Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Chen, Dan-Qing AU - Chen DQ AD - Shanghai SPH Shenxiang Health Medicine Co., Ltd., Shanghai, China. FAU - Wang, Dan-Dan AU - Wang DD AD - SPH XingLing Sci&Tech. Pharmaceutical Co., Ltd., Shanghai, China. FAU - Zhu, Guo-Qin AU - Zhu GQ AD - Shanghai University of Traditional Chinese Medicine, Shanghai, China. AD - SPH XingLing Sci&Tech. Pharmaceutical Co., Ltd., Shanghai, China. FAU - Gao, Qi AU - Gao Q AD - Shanghai University of Traditional Chinese Medicine, Shanghai, China. AD - SPH XingLing Sci&Tech. Pharmaceutical Co., Ltd., Shanghai, China. LA - eng PT - Journal Article DEP - 20220901 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC9474728 OTO - NOTNLM OT - CVD OT - GG OT - MCG OT - UPLC-Q-TOF/MS OT - network pharmacology OT - zebrafish COIS- Y-XZ, D-DW, G-QZ, and QG were employed by the company SPH XingLing Sci&Tech. Pharmaceutical Co., Ltd., and D-QC was employed by the company Shanghai SPH Shenxiang Health Medicine Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/09/20 06:00 MHDA- 2022/09/20 06:01 PMCR- 2022/09/01 CRDT- 2022/09/19 04:39 PHST- 2022/04/15 00:00 [received] PHST- 2022/07/19 00:00 [accepted] PHST- 2022/09/19 04:39 [entrez] PHST- 2022/09/20 06:00 [pubmed] PHST- 2022/09/20 06:01 [medline] PHST- 2022/09/01 00:00 [pmc-release] AID - 920979 [pii] AID - 10.3389/fphar.2022.920979 [doi] PST - epublish SO - Front Pharmacol. 2022 Sep 1;13:920979. doi: 10.3389/fphar.2022.920979. eCollection 2022.