Integrated metabolomics and network analysis reveal changes in lipid metabolisms of tripterygium glycosides tablets in rats with collagen-induced arthritis

Yanhua Gao; Qi Qian; Ge Xun; Jia Zhang; Shuo Sun; Xin Liu; Fangfang Liu; Jiachen Ge; Huaxing Zhang; Yan Fu; Suwen Su; Xu Wang; Qiao Wang

doi:10.1016/j.csbj.2023.02.050

Integrated metabolomics and network analysis reveal changes in lipid metabolisms of tripterygium glycosides tablets in rats with collagen-induced arthritis

Comput Struct Biotechnol J. 2023 Feb 28:21:1828-1842. doi: 10.1016/j.csbj.2023.02.050. eCollection 2023.

Authors

Yanhua Gao¹, Qi Qian¹, Ge Xun¹, Jia Zhang¹, Shuo Sun¹, Xin Liu¹, Fangfang Liu¹, Jiachen Ge¹, Huaxing Zhang², Yan Fu², Suwen Su³, Xu Wang¹, Qiao Wang¹

Affiliations

¹ School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, People's Republic of China.
² Core Facilities and Centers, Hebei Medical University, Shijiazhuang 050017, People's Republic of China.
³ Key Laboratory of Pharmacology and Toxicology for New Drugs, Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, People's Republic of China.

Abstract

Tripterygium glycosides tablets (TGT) are the commonly used preparation for rheumatoid arthritis (RA). However, the changes in TGT on RA are still unclear at the metabolic level. This study aimed to reveal the biological processes of TGT in collagen-induced arthritis (CIA) rats through integrated metabolomics and network analysis. First, the CIA model in rats was established, and the CIA rats were given three doses of TGT. Then, the endogenous metabolites in the serum from normal rats, CIA rats, and CIA rats treated with varying doses of TGT were detected by UHPLC-QTOF-MS/MS. Next, univariate and multivariate statistical analyses were performed to find the differential metabolites. Finally, differential metabolites, metabolic pathways, and hub genes were analyzed integrally to reveal the biological processes of TGT in CIA rats. The paw diameter, arthritis score, immunoglobulin G (IgG) concentration, CT image, and histological assay showed that TGT had evident therapeutic effects on CIA rats. Untargeted metabolomics revealed that TGT could ameliorate the down-regulation of lipid levels in CIA rats. Four key differential metabolites were found including LysoP(18:0), LysoPA(20:4), LysoPA(18:2), and PS(O-20:0/17:1). The glycerophospholipid metabolic pathway was perturbed in treating CIA with TGT. A total of 24 genes, including PLD1, LPCAT4, AGPAT1, and PLA2G4A, were found to be the hub genes of TGT in CIA rats. In conclusion, the integrated analysis provided a novel and holistic perspective on the biological processes of TGT in CIA rats, which could give helpful guidance for further TGT on RA. Future studies based on human samples are necessary.

Keywords: CDS, Calibrant Delivery System; CFA, Complete Freund’s adjuvant; CIA, collagen-induced arthritis; CUR, curtain gas; DMARDs, disease-modifying anti-rheumatic drugs; ESI, electrospray ionization; FC, fold change; GS1, nebulizer gas; GS2, heater gas; HMDB, Human Metabolome Database; IDA, Information Dependent Acquisition; IgG, immunoglobulin G; Lipid metabolisms; Metabolomics; Micro-CT, Micro-computed tomography; Network analysis; QC, quality control; RA, rheumatoid arthritis; ROC, Receiver operating characteristic; Rheumatoid arthritis; TGT, Tripterygium glycosides tablets; Tripterygium glycosides tablets; VIP, variable importance in projection.