Erodium stephanianum-Derived Polyphenols Prevented the Progression of Collagen-Induced Arthritis in Mice and Its Associated Metabolic Alterations.

Background

This study aimed to investigate the effects of E. stephanianum-derived polyphenols on preventing the progression of collagen-induced arthritis (CIA) in mice and its associated metabolic alterations.

Methods

The E. stephanianum plant was extracted, fractionated, and screened in vitro for anti-inflammatory, antibacterial, and antioxidant potential. Fraction 5 (identified as ellagic acid by nuclear magnetic resonance) exhibited the most potent activity and was selected for in vivo study. In the in vivo study, male DBA/1JGpt mice were randomized into five groups: control (CON), CIA (Model), low-dose extract (ES-L), high-dose extract (ES-H), and ellagic acid group. ES-L, ES-H, and ellagic acid were administered by daily oral gavage at 375, 750, and 250 mg/kg body weight, respectively, for 8 weeks. Arthritis severity was evaluated based on paw thickness, clinical score, ankle joint histopathology, and serum proinflammatory cytokine levels. To reveal the associated metabolic alterations, serum metabolites were characterized by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

Results

Both the whole extract and ellagic acid revealed pronounced anti-inflammatory, antibacterial, and antioxidant properties. In vivo treatment with ES-L, ES-H, or ellagic acid similarly and significantly ameliorated CIA severity, showing smaller paw swelling, reduced clinical arthritis scores, milder joint histopathological injury, and lower serum tumor necrosis factor-α and interleukin-6 concentrations than the model group. Untargeted metabolomics identified 20 differential metabolites, mainly including triacylglycerols (containing n-3 fatty acids), pro-inflammatory phospholipids, and spermic acid 1. Moreover, the treatments significantly altered amino acid and purine metabolism.

Conclusions

E. stephanianum derived polyphenols, like ellagic acid, significantly prevented the progress of CIA in mice. These effects were associated with the alteration of metabolic profiles.