Anti-inflammatory mechanism of the optimized active ingredients of Sargentodoxa cuneata and Patrinia villosa

Abstract

Pelvic inflammatory disease (PID) is a common gynecological infection. The combined use of Sargentodoxa cuneata (da xue teng) and Patrinia villosa (bai jiang cao) has been shown to inhibit PID progression. The active components of S. cuneata (emodin, Emo) and P. villosa (acacetin, Aca; oleanolic acid, OA; sinoacutine, Sin) have been identified but the mode of action of this combination of compounds against PID has not been clarified. Therefore, this study aims to investigate the mechanism of these active components against PID through network pharmacological, molecular docking and experimental validation. The results showed the optimal combination of components was 40 µM Emo + 40 µM OA, 40 µM Emo + 40 µM Aca, and 40 µM Emo + 150 µM Sin by cell proliferation and NO release. The potential key targets of this combination in the treatment of PID include SRC, GRB2, PIK3R1, PIK3CA, PTPN11, and SOS1, which act on signaling pathways such as EGFR, PI3K/Akt, TNF, and IL-17. Emo, Aca, OA, and their optimal combination inhibited the expression of IL-6, TNF-α, MCP-1, IL-12p70, IFN-γ, and the M1 phenotype markers CD11c and CD16/32, and promoted the expression of the M2 phenotype markers CD206 and arginase 1 (Arg1). Western blotting confirmed that Emo, Aca, OA, and their optimal combination significantly inhibited the expression of glucose metabolism-related proteins PKM2, PD, HK I, and HK II. This study proved the advantage of combination use of active components from S. cuneata and P. villosa, and clarified that they exert the anti-inflammatory effect by regulation of M1/M2 phenotype transition and regulation of glucose metabolism. The results provide a theoretical basis for the clinical treatment of PID.