Effect and mechanism of Rhei radix et Rhizoma-Bupleuri radix drug pair for alcoholic liver disease based upon network pharmacology and animal experiments
OBJECTIVE To explore the effect and mechanism of Dahuang(Rhei radix et Rhizoma,RRR)-Chaihu(Bupleuri radix,BR)drug pair for alcoholic liver disease(ALD).METHODS The targets and pathways of RRR-BR herb pair for ALD were predicted by network pharmacology.ALD model of rats was established by an intragastric injection of 56° liquor.After 7-day intervention with traditional Chinese medicine decoction,the effects of each group on ethanol concentration and serum activities of alcohol dehydrogenase(ADH)and acetaldehyde dehydrogenase(ALDH)were detected.The effects of each dosing group on hepatic pathological morphology were examined by hematoxylin-eosin(HE)and oil red O stain.The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC),very low-density lipo-protein(VLDL),reactive oxygen species(SOD)and malondialdehyde(MDA)in sera or liver homogenate of rats were detected.RESULTS A total of 36 active components and 218 targets for treating ALD were obtained by network pharmacology analysis.The core targets involved TP53,MAPK1,AKT1,TNF,CYP2E1,PPARα,ADH and ALDH.Its effect might be correlated with lipid and atherosclerosis,signaling pathways of PI3K-Akt,MAPK & TNF,ALD and other signaling pathways.As com-pared with model group,RRR-BR herb pair could significantly improve the pathological changes of rat liver,significantly reduce blood ethanol concentration(P＜0.05),enhance the serum activity of ADH/ALDH(P＜0.05),blunt the serum activity of AST/ALT(P＜0.05,P＜0.01),decrease the serum contents of TG/VLDL(P＜0.05),reduce the hepatic contents of TC,TG and VLDL(P＜0.05,P＜0.01),lower the content of MDA(P＜0.05)and boost the content of SOD(P＜0.01).CONCLUSION RRR-BR drug pair has the effect of treating ALD in rats.Its mechanism may be correlated with the regulation of PI3K-Akt,MAPK,ALD and other signaling pathways,acting on ADH,ALDH and other targets,thereby accelerating etha-nol and acetaldehyde metabolism,blunting fat accumulation and minimizing oxidative damage.
Rhei radix et RhizomaBupleuri radixnetwork pharmacologyalcoholic liver disease
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