Chemical constituents and hepatoprotective properties of Rhododendron simsii Planch extract in Con A-induced autoimmune hepatitis

Rhododendron simsii Planch, a folk medicine recorded in the ‘Dictionary of Chinese Materia Medica’, has been used by many ethnic regions of China to treat various inflammatory and immune-related diseases such as skin disorders and rheumatoid arthritis. However, its protective effect against autoimmune hepatitis and the underlying mechanisms remain unclear. The present study aimed to aimed to investigate the protective effects on autoimmune hepatitis through an integrated approach established by combining chemical composition identification, network pharmacology and in vivo experimental validation. Animal experiments showed that R. simsii Planch extract ameliorated ConA-induced liver injury, as evidenced by a reduction in ALT and AST levels and varying degrees of improvement in liver histopathology, with the R-EE (R. simsii Planch EtOAc extract) treated group showing the most obvious therapeutic effect. Then, chemical investigations into R-EE yielded 15 flavonoid and phenolic acid derivatives namely quercetin 3-O-α-L-rhamnoside (1), tamarixetin 3-rhamnoside (2), isoquercitrin (3), hyperoside (4), myricetin-3-O-α-L-rhamnopyranoside (5), afzelin (6), quercetin-3-O-α-L-arabinofuranoside (7), quercetin-3-O-α-D-arabinopyranoside (8), (+)-catechin (9), kaempferol (10), dihydromyricetin (11), quercetin (12), vanillic acid (13), gallic acid (14) and farrerol (15). Further network pharmacological analysis indicated that the potential mechanism against ConA-induced liver injury is probably related to the regulation of the NF-κB signaling pathway. Experiments confirmed that R-EE could reduce liver damage and downregulate CD4+ and inflammatory cytokine levels and the expressions of NLPR3, COX-2 and p-IκBα, and exhibited considerable hepatoprotective effects in ConA-induced AIH mice, which may be related to its flavonoids, and the underlying mechanism may involve the regulation of the NF-κB signaling pathway. The present results indicated that R. simsii Planch extract has more therapeutic potential in the treatment of autoimmune hepatitis, and provide the experimental basis for traditional application of R simsii Planch in the treatment of inflammatory diseases, and is a potential treatment agent for AIH that deserves further study.