[Effect of Bupleuri Radix-Paeoniae Radix Albae combination on HMGB1/RAGE/NF-κB signaling pathway in rats with...

To explore the effect of the combination of Bupleuri Radix and Paeoniae Radix Alba on the high mobility group box-1 protein(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-κB(NF-κB) signaling pathway in rats with cholestatic hepatitis induced by rifampicin(RFP). Forty-two male SD rats were randomly divided into the normal group, the Bupleuri Radix-Paeoniae Radix Alba group(C-B group), the RFP group, the ursodeoxycholic acid(UDCA)+RFP group(UDCA+RFP group), the Bupleuri Radix+RFP group(C+RFP group), the Paeoniae Radix Alba+RFP group(B+RFP group), and the Bupleuri Radix-Paeoniae Radix Alba+RFP group(C-B+RFP group). RFP was administered by gavage to establish a cholestatic hepatitis model, and the corresponding drugs were administered simultaneously in the treatment groups for 14 days. The physiological state and body weight of the rats were observed and recorded daily. After the experiment, hematoxylin-eosin(HE) staining was used to observe the pathological morphology of the liver; the terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL) method was used to observe the apoptosis of liver cells; the activities or contents of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), total bilirubin(TBIL), direct bilirubin(DBIL), and total bile acids(TBA) in serum were detected. The mRNA and protein expression levels of HMGB1, RAGE, NF-κB p65, interleukin(IL)-1β, tumor necrosis factor(TNF)-α, IL-6, glucose-regulated protein 78(GRP78), and CCAAT/enhancer-binding protein homologous protein(CHOP) were detected by quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot. The results show that compared with the normal group, RFP group exhibited decreased body weight, listlessness, disordered hepatic cord structures, present inflammatory cells, and increased numbers of apoptotic cells. The serum activities or contents of ALT, AST, ALP, TBIL, DBIL, and TBA were significantly increased. The mRNA and protein expression levels of HMGB1/RAGE/NF-κB signaling pathway factors, IL-1β, TNF-α, IL-6, GRP78, and CHOP were also significantly increased, indicating the successful establishment of the cholestatic hepatitis model. Compared with the RFP group, the UDCA+RFP, C+RFP, B+RFP, and C-B+RFP groups showed increased body weight, improved abnormal pathological conditions in liver tissue, and decreased activities or contents of serum ALT, AST, ALP, TBIL, DBIL, and TBA. The mRNA and protein expression levels of HMGB1/RAGE/NF-κB signaling pathway factors, IL-1β, TNF-α, IL-6, GRP78, and CHOP in liver tissue were also decreased. Compared with the C-B+RFP group, the ALT activity and the protein expression levels of HMGB1, RAGE, IL-6, and GRP78 were significantly higher in the C+RFP and the B+RFP groups. In conclusion, the combination of Bupleuri Radix and Paeoniae Radix Alba alleviates endoplasmic reticulum stress through the HMGB1/RAGE/NF-κB signaling pathway and reduces inflammatory responses, thereby exerting hepatoprotective effects.