Filtering of Active Components of Fuzi Lizhong Decoction on Gastric Ulcer by UHPLC/Q-Exactive MS Uniting Network Pharmacology

Abstract

To filter the active components of Fuzi Lizhong decoction (FLD) treating gastric ulcer (GU), compound information of herbs making up FLD was collected. Components in FLD extract were identified using ultrahigh performance liquid chromatography coupled with quadrupole-exactive orbitrap mass spectrometry (UHPLC/Q-Exactive MS). After that, network pharmacology and molecular docking were applied for predicting active components. Next, GES-1 cell survival rate experiments were conducted to verify the active components. At last, real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was applied to confirm active components. Results showed that a total of 58 components in FLD were qualified and 55 of them functioned on 310 GU-relevant targets, involved in 154 signaling pathways. Through molecular docking of the top 30 components with the top 30 targets and referring to the reference, 9 components and their targets were predicted to be active components. Among them, atractylenolide II, tyrosine, and atractylenolide III were verified to inhibit GES-1 cell apoptosis, confirmed to reverse the gene expression of GU-relevant targets involving PPARG, EGFR, MAPK1, and ESR1 in GES-1 cells. So, atractylenolide II, tyrosine, and atractylenolide III were considered as active components of FLD treating GU. In conclusion, active components of FLD treating GU were filtered by applying UHPLC/Q-Exactive MS, uniting network pharmacology with the assistance of molecular docking and RT-qPCR. FLD might exert anti-GU effect through atractylenolide II, tyrosine, and atractylenolide III functioning as the relevant targets.