标题:Untargeted Metabolomics Study of the In Vitro Anti-Hepatoma Effect of Saikosaponin d in Combination with NRP-1 Knockdown
作者:Lv, Yingtong; Hou, Xiaoying; Zhang, Qianqian; Li, Ruiting; Xu, Lei; Chen, Yadong; Tian, Yuan; Sun, Rong; Zhang, Zunjian; Xu, Fengguo
作者机构:[Lv, Yingtong; Hou, Xiaoying; Zhang, Qianqian; Li, Ruiting; Xu, Lei; Tian, Yuan; Zhang, Zunjian; Xu, Fengguo] China Pharmaceut Univ, State Key Lab Nat 更多
通讯作者:Zhang, ZJ;Xu, FG;Zhang, ZJ;Xu, FG
通讯作者地址:[Zhang, ZJ; Xu, FG]China Pharmaceut Univ, State Key Lab Nat Med, Minist Educ, Key Lab Drug Qual Control & Pharmacovigilance, Nanjing 210009, Jiangsu, 更多
来源:MOLECULES
出版年:2019
卷:24
期:7
DOI:10.3390/molecules24071423
关键词:saikosaponin d; neuropilin-1; HepG2; metabolomics; metabolite; deregulation score
摘要:Saikosaponin d (SSd) is one of the main active ingredients in Radix Bupleuri. In our study, network pharmacology databases and metabolomics were used in combination to explore the new targets and reveal the in-depth mechanism of SSd. A total of 35 potential targets were chosen through database searching (HIT and TCMID), literature mining, or chemical similarity predicting (Pubchem). Out of these obtained targets, Neuropilin-1 (NRP-1) was selected for further research based on the degree of molecular docking scores and novelty. Cell viability and wound healing assays demonstrated that SSd combined with NRP-1 knockdown could significantly enhance the damage of HepG2. Metabolomics analysis was then performed to explore the underlying mechanism. The overall difference between groups was quantitatively evaluated by the metabolite deregulation score (MDS). Results showed that NRP-1 knockdown exhibited the lowest MDS, which demonstrated that the metabolic profile experienced the slightest interference. However, SSd alone, or NRP-1 knockdown in combination with SSd, were both significantly influenced. Differential metabolites mainly involved short- or long-chain carnitines and phospholipids. Further metabolic pathway analysis revealed that disturbed lipid transportation and phospholipid metabolism probably contributed to the enhanced anti-hepatoma effect by NRP-1 knockdown in combination with SSd. Taken together, in this study, we provided possible interaction mechanisms between SSd and its predicted target NRP-1.
收录类别:SCOPUS;SCIE
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064692088&doi=10.3390%2fmolecules24071423&partnerID=40&md5=6e20c6312f6459b2a0963d42e8dfd796
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