Metabolomics Combined with Network Pharmacology to Explore the Active Components and Mechanism of Tetrastigma planicaule (Hook.) Gagnep. in the Treatment of Rheumatoid Arthritis

Abstract

Context. Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. It is characterized by persistent joint damage. Traditional Chinese medicine (TCM) has demonstrated notable efficacy in managing RA. Prior investigations have indicated that the ethyl acetate extract of Tetrastigma planicaule (Hook.) Gagnep. (TP) possesses substantial anti-inflammatory properties, suggesting the potential for screening TCM drugs with antirheumatoid arthritis attributes. However, the precise mechanism underlying its pharmacological effects and material basis remains unclear, impeding the advancement of TCM innovation. Objective. This study is to elucidate the active components and mechanism of TP in the treatment of RA. Materials and Methods. A rat model of collagen-induced arthritis (CIA) was established for conducting pharmacological experiments to assess the effectiveness of ethyl acetate extract from TP in treating RA. In addition, nuclear magnetic resonance (NMR) metabolomics technology was employed to identify potential endogenous biomarkers for further metabolic pathway analysis. The active compounds and key targets were investigated using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) technology in combination with network pharmacology. Moreover, common gene targets discovered by metabolomics and network pharmacology were validated by molecular docking with the relevant active components. Result. 12 endogenous biomarkers were screened by 1H-NMR metabolomics technology. The metabolite pathways are primarily implicated in lipid metabolism and amino acid metabolism. 49 compounds were identified in TP, of which 10 were considered active ingredients through network pharmacological analysis. In a comprehensive analysis, it was found that TP exhibited a strong association with the PLA2G4A and lipid metabolite pathways in RA. Molecular docking studies further demonstrated a high affinity between the active compounds of TP and PLA2G4A. Discussion and Conclusions. TP may play a therapeutic role in RA by regulating PLA2G4A and participating in back-regulating the glycerophospholipid metabolic pathway. The study elucidated the multicomponent, multitarget, and multipathway mechanism of TP in the treatment of RA, laying the groundwork for a deeper understanding of its therapeutic mechanisms.