Effect and mechanism of YAO medicine compound containing Cissus pteroclada on rheumatoid arthritis in rats and its Q-marker prediction / 中草药

ABSTRACT

Objective: To evaluate the anti-rheumatism effect, and predict the mechanism and Q-marker of YAO medicine compound containing Cissus pteroclada (Sifangteng in Chinese, SFT) in the treatment of rheumatoid arthritis (RA) in rats. Methods: SD rats were randomly divided into control group, model group, tripterygium glycosides group and SFT high/low dose (28.7, 7.2 g/kg) groups with eight rats in each group. Except the control group, the RA models in rats induced by Collange II collagen were established. The SFT group and the tripterygium glycosides group were given corresponding drugs by intragastric administration during the modeling period, while the other two groups were given the same volume of saline once daily for 28 d. The degree of foot swelling was measured and scored during the experiment. The levels of TNF-α and IL-1β in serum were measured by ELISA at the end of the experiment. SFT chemical components and predicting targets were searched and screened through TCMSP and Drugbank databases. The target of RA disease was searched by TTD database. The protein interaction network was constructed and visualized by String database and Cytoscape software, cluster analysis was analyzed by MCODE. GO and KEGG enrichment analysis was carried out using String database. Finally, combined with the validity and measurability of chemical components, the Q-marker of SFT was predicted. Results: Compared with the model group, the foot swelling of rats in SFT high and low dose groups and positive group was significantly reduced (P < 0.01), and the serum levels of IL-1β and TNF-α were significantly decreased (P < 0.01). There were 89 disease targets of RA. The pathogenesis of RA was related to abnormal cytokine-receptor pathway and RA pathway. A total of 31 components in SFT were screened and its 119 target proteins were predicted, 12 of them belong to disease targets were involved in 1 112 biological processes, such as regulation of stimulation response, regulation of cell proliferation, regulation of cell metabolism, regulation of intracellular signal transduction, and regulation of 113 signaling pathways, such as RA pathway and TNF pathway, which ultimately play a role in the treatment of RA. At the same time, 11 components were predicted to be Q-markers of SFT, including apigenin, resveratrol, bergenin, nitidine, osthol, linalool, ammidin, ethoxychelerythrine, coptisine, hesperidin, and sesamin. Conclusion: SFT can significantly reduce acute inflammation in RA rats. SFT may act on PTGS2-based targets through resveratrol and other components, and participate in regulation of RA pathway, TNF pathway and other inflammatory and immune pathways. Apigenin, resveratrol and bergenin, nitidine, osthol, linalool, ammidin, ethoxychelerythrine, coptisine, hesperidin, sesamin can be used as Q-markers for SFT quality control.