The edible and medicinal part ofInula nervosaWall. (Xiaoheiyao) is confined to its root without sufficient phytochemical and biological investigation. In this study, the secondary metabolites of root, stem, leaf, and flower ofI. nervosaWall. were visualized using Global Natural Products Social Molecular Networking (GNPS), MolNetEnhancer, XCMS(xcmsonline.scripps.edu) analysis, and `ili mapping based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) data to reveal their chemical differences. Among the 11 kinds of chemical repertoires annotated by MolNetEnhancer and 16 hits against the GNPS library, 10-isobutyryloxy-8,9-epoxythymol isobutyrate (1) was revealed as the most dominant and responsible marker between the roots and the other parts. Moreover, a battery of unique MS features as well as differential markers were discovered from different parts of the plant. The chemical differences contribute to the bioactivity differences, which presented in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH)assay and H2O2-insulted HepG2 cells and were in significant correlations with the contents of1. real-time reverse transcription polymerase chain reaction (RT-PCR)results demonstrated thatI. nervosaWall. extracts upregulated the mRNA expression of nuclear factor E2-related factor 2(Nrf2), heme oxygenase 1(HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), manganese superoxide dismutase (MnSOD), and glutamate-cysteine ligase catalytic subunit (GCLC) actors involved in antioxidative response in H2O2-challenged HepG2 cells. These findings support the roots ofI. nervosaWall. as active parts ofXiaoheiyao, and also indicate the potential antioxidant activities of other parts.Keywords:Xiaoheiyao;GNPS molecular networking;MolNetEnhancer;XCMS online;Nrf2
Xiaoheiyao is the rhizome of Inula nervosa Wall., a traditional spice and medicinal herb in China. In this study, the creatinine inhibitor from Xiaoheiyao extract and also the effects and mechanism on the production of heterocyclic aromatic amines (HAAs) were investigated. Xiaoheiyao extract inhibited the total contents of seven detected HAAs in grilled beef patties, particularly aminoimidazole-azaarenes (AIAs) in a dose-dependent manner, reaching a maximum inhibition rate of 62% for total HAAs and 73% for AIAs. The most effective subfraction of Xiaoheiyao extract (IER80) contained abundant potential creatinine inhibitors, as revealed by immobilized creatinine probe, HPLC and UPLC-MS/MS analyses. Moreover, electrophilic p -coumaric acid derivatives were discovered from IER80 by feature based molecular networking. p -Coumaric acid was demonstrated to inhibit the contents of total HAAs and AIAs in grilled beef patties and model system. Quantitative analyses of the precursor and intermediates of AIAs in model system revealed that p -coumaric acid mainly affected the generation of AIAs by inhibiting creatinine.
Xiang-Rong Cheng,Piao-Han Tu,Wen-Le Dong,Bu-Tao Yu,Shu-Fang Xia,Mitchell N. Muskat,Bin Guan
Xiaoheiyao , the rhizomes of Inula nervosa Wall., is a culinary spice known to contain some electrophilic Nrf2 activators that could potentially intervene in nonalcoholic fatty liver disease (NAFLD). In this study, the electrophilic components from Xiaoheiyao were annotated by comprehensive cheminformatics analyses on UHPLC-MS/MS data after being knocked out with glutathione (GSH)-immobilized magnetic microspheres. Their intervention effects against hepatic steatosis were investigated in free fatty acid (FFA)-treated HepG2 cells. The electrophilic components in Xiaoheiyao were found to be the major bioactive components preventing hepatic steatosis in FFA-treated HepG2 cells. In particular, 10-isobutyryloxy-8,9-epoxythymol isobutyrate (XHY-1) improved hepatic lipid metabolism disorder, Krebs cycle activity, oxidative phosphorylation, and the cellular and mitochondrial redox status. Moreover, XHY-1 activates the Nrf2-ARE signaling pathway through the up-regulation of Nrf2 expression and promotion of Nrf2 nuclear translocation. Molecular docking further showed that XHY-1 could conjugate with Cys151 in the BTB domain of Keap1 through the epoxy group. In conclusion, the electrophilic components of Xiaoheiyao , especially XHY-1, attenuated hepatic steatosis in FFA-treated HepG2 cells through activation of the Nrf2-ARE signaling pathway.
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