Plasma metabonomic study on Zushima Gancao Tablet in treatment of rheumatoid arthritis based on UPLC/LTQ-Orbitrap-MS / 中草药

ABSTRACT

Objective: To observe the regulating action of Zushima Gancao Tablet on abnormal metabolites by analyzing the changes of endogenous metabolites in plasma of rheumatoid arthritis (RA) rats, and to explore the mechanism of Zushima Gancao Tablet in treating RA from the perspective of metabonomics. Methods: Rats were divided into normal group (NG), model group (MG), positive medicine group (PMG), and Zushima Gancao Tablet group (ZGG). Adjuvant arthritis (AA) rats were established with freund complete adjuvant, rats in PMG and ZGG groups were ig administered with tripterygium glycosides and Zushima Gancao Tablet respectively for a month. Plasma samples were collected on days 1, 10, 20, and 28 before and after administration. UPLC/LTQ-Orbitrap-MS was applied to analyzing the metabolic profile changes of each group in different durations of the disease and mechanism of drug intervention. Results: The related pathways of AA mainly involved metabolisms of amino acids, lipids, nucleic acids, and vitamins. Zushima Gancao Tablet had great effect on AA by regulating 12 biomarkers. Conclusion: Small molecule metabolites in AA rats are deviated from the normal ones. The effects of Zushima Gancao Tablet and positive medicine (tripterygium polyglycoside) on AA are similar, but the mechanisms were different. Zushima Gancao Tablet down-regulates the level of LPC in secondary lesions while tripterygium polyglycoside tablets could effectively inhibit the metabolisms of a variety of amino acids during acute inflammation.