Paeoniae Radix Rubra and Moutan Cortex Modulate `NF-κB` Pathway, Reducing Inflammation in Lupus Models

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread inflammation and organ damage, with limited targeted therapies. Current treatments often rely on broad immunosuppressants, which carry significant side effects and don't address the underlying molecular pathology comprehensively. Traditional Chinese Medicine (TCM) offers potential alternative or complementary approaches, but their precise molecular mechanisms in complex diseases like SLE are often underexplored. This study investigates the therapeutic potential of Paeoniae Radix Rubra (CS) and Moutan Cortex (MDP), two commonly used herbs in SLE management, by elucidating their specific molecular targets and pathways.

Researchers utilized a network pharmacology approach to identify potential active ingredients and targets of CS-MDP. They screened the TCMSP database for compounds and their targets, cross-referencing with known SLE disease targets from other databases using Venny 2.1.0. Network enrichment analysis (GO, KEGG) was performed with R 4.0.5, followed by molecular docking using AutoDock Vina 1.1.2. In vitro, LPS-challenged RAW264.7 cells were treated with CS-MDP. In vivo, MRL/lpr lupus mice were also treated with CS-MDP. Primary endpoints included mRNA expression of pro-inflammatory cytokines and protein expression of the NF-κB signaling pathway.

Network pharmacology identified 21 potential active ingredients and 208 targets for CS-MDP, with 111 intersection targets relevant to SLE. GO enrichment analysis revealed 1987 terms, primarily linked to cellular response to chemical stress and regulation of peptide secretion. KEGG analysis identified 185 signaling pathways, notably Lipid and atherosclerosis and Hepatitis B. > In vitro, CS-MDP significantly 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. Furthermore, in vivo experiments demonstrated that CS-MDP also downregulated the protein expression of the NF-κB signaling pathway in MRL/lpr lupus mice. This suggests a consistent anti-inflammatory effect across both cellular and animal models, mediated through the modulation of the NF-κB pathway and subsequent reduction in pro-inflammatory cytokine expression.