Study on the Effect of Puerarin-Gadolinium on Rheumatoid Arthritis Rats based on Nontargeted Metabolomics Technology

Area of Science:

• Metabolomics
• Pharmacology
• Rheumatology

Background:

• Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint damage.
• Identifying novel therapeutic targets and understanding disease mechanisms are crucial for RA treatment.
• Metabonomics offers a powerful approach to uncover biomarkers and metabolic alterations in RA.

Purpose of the Study:

• To investigate the therapeutic effects of puerarin-gadolinium on a rat collagen-induced arthritis (CIA) model.
• To identify potential biomarkers and metabolic pathways associated with RA using joint tissue metabolomics.
• To elucidate the mechanism of action of puerarin-gadolinium in treating RA.

Main Methods:

• Establishment of a stable rat collagen-induced arthritis (CIA) model.
• Treatment with puerarin, puerarin-gadolinium, gadolinium chloride, methotrexate, or saline.
• Analysis of joint tissue metabolomics using Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS).
• Evaluation of therapeutic efficacy through morphological, histopathological, and biochemical indicators.

Main Results:

• Puerarin-gadolinium demonstrated significant therapeutic efficacy in the rat RA model, outperforming puerarin, gadolinium chloride, and methotrexate.
• Metabolomic analysis revealed significant alterations in metabolite profiles in the RA model, with 238 differentially expressed metabolites compared to controls.
• Treatment with puerarin-gadolinium resulted in 165 downregulated differentially expressed metabolites, suggesting a normalization of metabolic pathways.
• Enriched pathways included linoleic acid metabolism, α-linolenic acid metabolism, arachidonic acid metabolism, and choline metabolism, indicating a role in lipid metabolism and ferroptosis.

Conclusions:

• Puerarin-gadolinium exhibits significant therapeutic potential for rheumatoid arthritis.
• The mechanism of action may involve the inhibition of ferroptosis and the regulation of lipid metabolism pathways.
• Metabolomics is a valuable tool for understanding RA pathogenesis and evaluating novel therapeutic interventions.