Network pharmacology and experimental analysis of Paeoniae radix Rubra and moutan cortex for SLE treatment

Paeoniae Radix Rubra (Chishao, CS) and Moutan Cortex (Mudanpi, MDP) are frequently utilized in the clinical management of SLE, yet the molecular mechanisms underlying their therapeutic effects in SLE remain to be fully elucidated. This study aims to investigate the mechanism of CS-MDP in treating SLE using a network pharmacology and experimental approach. The potential active ingredients and targets of CS-MDP were obtained through screening the TCMSP database. Known targets of SLE were retrieved from disease databases, and the intersection targets of CS-MDP in treating SLE were obtained using the Venny 2.1.0 online platform. Network enrichment analysis of the intersection targets was performed using R 4.0.5 software. Molecular docking of the core ingredients and targets was carried out using AutoDock Vina 1.1.2. Finally, the mechanism of CS-MDP against SLE was verified through in vivo and in vitro experiments. CS-MDP was found to have 21 potential active ingredients and 208 targets. A total of 111 intersection targets were determined for CS-MDP in treating SLE. GO enrichment analysis identified 1987 terms, mainly enriched in cellular response to chemical stress and regulation of peptide secretion. KEGG analysis identified 185 signaling pathways, with main enrichments in Lipid and atherosclerosis, and Hepatitis B. In vitro, CS-MDP inhibited the mRNA expression of TNF-α, IL-1β, and IL-6, and downregulated the protein expression of the NF-κB signaling pathway in LPS-challenged RAW264.7 cells. In addition, CS-MDP also downregulated the protein expression of the NF-κB signaling pathway in MRL/lpr lupus mice. In conclusion, this study suggests that CS-MDP may exert therapeutic effects on SLE, potentially by modulating the NF-κB signaling pathway and consequently inhibiting the expression of pro-inflammatory cytokines.