Exploration of the oxidative-inflammatory potential targets of Coicis Semen in osteoarthritis: Data mining and systematic pharmacology

Abstract

Objective: On the basis of data mining, systematic pharmacology, molecular docking, and experiment validation, the oxidative-inflammatory molecular targets of Coicis Semen in the therapy of osteoarthritis (OA) were explored. Methods: The association rule analysis was effectively applied to highlight the correlation between Coicis Semen and oxidative inflammation indices. The random walk model was subsequently used to evaluate the clinical efficacy of Coicis Semen. Network pharmacology was used to predict network targets. The binding affinity of the active ingredient in Coicis Semen to the key target of OA was also successfully predicted. Results: Coicis Semen showed a significant reduction in oxidative-inflammatory indicators of OA. A total of 108 promising targets were predicted for the 24 bioactive compounds in Coicis Semen. Eight target genes were considered core target genes. The enrichment analysis predicts that Coicis Semen may activate the interleukin (IL)-17, mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-kappa B) signaling pathways. Molecular docking demonstrated that stigmasterol, 2-monoolein, sitosterol, and sitosterol alpha1 had free binding energies to oxidative and inflammatory targets (MAPK1, Estrogen Receptor 1 [ESR1], and Peroxisome Proliferator-Activated Receptor Alpha [PPARA]). Both clinical trials and in vitro cell experiments revealed that Coicis Semen could increase ESR1 and PPAR-α levels while decreasing MAPK1 levels. Conclusions: Coicis Semen has a remarkable anti-OA effect. Precisely, the major components of Coicis Semen, including stigmasterol, sitosterol alpha1, sitosterol, and 2-monoolein, specifically inhibit MAPK1, ESR1, and PPARA to reduce the inflammatory response and oxidative damage in OA.