NMR-based untargeted metabolomics approach to investigate the systemic lipid metabolism regulation of norisoboldine in collagen-induced arthritis rats

Norisoboldine (NOR), an isoquinoline alkaloid, has previously been shown to ameliorate collagen-induced arthritis (CIA) by modulating the function of multiple cells such as T lymphocytes and fibroblast-like synoviocytes. To further study its anti-arthritis mechanism, the effect of NOR on the systemic metabolism regulation was investigated using an NMR-based untargeted metabolomics approach. CIA model rats were orally administered with NOR (30 mg/kg) for 14 consecutive days. The alterations of endogenous metabolites in the urine samples were quantified by 1H NMR. While NOR significantly mitigated CIA in rats as evidenced by the reduced clinical scores and histopathological changes, the results indicated that the treatment restored the levels of 22 metabolites that were significantly changed by arthritis, and most of which were related to lipid metabolism. Further studies demonstrated that NOR up-regulated the expression of carnitine palmitoyltransferase 1 (CPT-1) and down-regulated the expression of fatty acid synthase (FASN) in the spleens and the synovial tissues of CIA rats. Together these results revealed a strong association between RA and the system in metabolic disorders. The differential metabolites and their related pathways may also serve as novel therapeutic targets for RA.