[Serum metabolomics unveils intervention mechanism of different processed products of Strychni Semen in rat model of rheumatoid arthritis].

Serum metabolomics was employed to investigate the effects of different processed products of Strychni Semen on the metabolic level in the rat model of rheumatoid arthritis(RA) and explore the metabolic mechanisms. One hundred female SD rats were allocated into blank control, model, positive control, raw Strychni Semen, high-, medium-, and low-dose vinegared Strychni Semen, urine-soaked Strychni Semen, deep-fried Strychni Semen, and sand-scalded Strychni Semen groups(n=10). Rats were injected with complete Freund's adjuvant(CFA) for the modeling of adjuvant arthritis(AA) and then treated with the decoctions of different processed products of Strychni Semen. The arthritis index(AI) score was recorded according to the degree of foot swelling in rats, and the immune organ indexes of rats in each group were examined. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) in the serum were determined by enzyme-linked immunosorbent assay(ELISA). The differential metabolites in the serum were screened by liquid chromatography-mass spectrometry(LC-MS) coupled with multivariate statistical analysis. The Human Metabolome Database(HMDB) was used to identify the differential metabolites, and MetaboAnalyst 6.0 was employed to enrich the pathways involving the differential metabolites. Strychni Semen and its different processed products reduced the AI score, immune organ indexes, and serum levels of TNF-α, IL-1β, and IL-6 in model rats. Serum metabolomics screened out a total of 55 potential biomarkers for different processed products of Strychni Semen. Metabolic pathway enrichment analysis showed that the therapeutic effects of Strychni Semen were mainly related to 12 key metabolic pathways, including glycerophospholipid metabolism, interconversion of pentose and glucuronide, degradation of valine, leucine, and isoleucine, ascorbic acid and glycuronate metabolism, and β-alanine metabolism. In conclusion, different processed products of Strychni Semen exert therapeutic effects on RA, and their therapeutic mechanisms are related to inflammation inhibition, glycerophospholipid metabolism, interconversion of pentose and glucuronide, degradation of valine, leucine, and isoleucine, and regulation of β-alanine.