Study on the promoting toxicity-reducing effect of Rhizoma Dioscoreae Bulbiferae introduced by major active ingredients from the processing of Glycyrrhizae Radix et Rhizoma juice and its mechanism
Objective:To explore the detoxification effect of the two major active ingredients,liquiritin(LQ)and glycyrrhizic acid(GA),introduced from the processing of Glycyrrhizae Radix et Rhizoma juice on the main toxic hepatotoxicity induced by diosbulbin B(DB)as the main toxic ingredient of Rhizoma Dioscoreae Bulbiferae,and its mechanism.Methods:On the basis of previous findings that the Glycyrrhizae Radix et Rhizoma juice preparation method can reduce the main toxic liver toxicity and enhance cough relieving and phlegm eliminating effects of Rhizoma Dioscoreae Bulbiferae,and the processing detoxification mechanism involves the introduction of the main active ingredients LQ and GA of Glycyrrhizae Radix et Rhizoma juice as processing excipients,as well as the inhibition of DB content,this study further verified the detoxification effect of the introduced main active components LQ and GA on the main toxic liver toxicity induced by DB through the detection and analysis of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)levels,and pathological staining of liver tissue.Further,focusing on the main mechanism of DB-induced hepatotoxicity,inflammation and oxidative damage,the attenuation mechanism was preliminarily explored.Results:Compared with the control group,the administration of DB significantly increased the serum ALT,AST,and ALP levels in mice(P＜0.01),and hepatocyte degeneration,inflammatory infiltration,and congestion in liver,and significantly up-regulated the levels of phosphorylated nuclear factor kappa-B(p-NF-κB)/cyclooxygenase-2(COX-2)proteins,and significantly down-regulated the expression levels of liver phosphorylated phosphatidylinositol 3 kinase/protein kinase B(p-PI3K/p-Akt),nuclear factor erythroid-2-related factor 2(Nrf2)protein(P＜0.01).Conversely,the intervention of the main active ingredients(LQ,GA)reversed the abnormalities of the above indicators to varying degrees(P＜0.05,P＜0.01).Notably,from the analysis of ALT and AST levels,LQ showed a higher attenuating effect than GA on the major toxic hepatotoxicity induced by DB by 3.3％and 2.8％,respectively.From the analysis of ALP level,GA was 7.1％higher than that of LQ on the attenuation of the main toxic hepatotoxicity induced by DB.From the analysis of the key molecules NF-κB and COX-2 in the inflammatory signaling pathway,the inhibitory effect of LQ on liver inflammation response induced by DB was 3.2％and 2.5％higher than that of GA,respectively.According to the analysis of Nrf2,the core molecule of anti-oxidation signaling pathway,GA was 18.2％higher than LQ in the up-regulating effect on the low liver antioxidant level induced by DB.Conclusion:Two major active ingredients introduced from the processing of Glycyrrhizae Radix et Rhizoma juice,LQ and GA,can attenuate the main toxic hepatotoxicity induced by DB,and the detoxification mechanism involved in inhibiting the NF-κB/COX-2 signal-mediated liver inflammatory response and enhancing the antioxidant defense mediated by the transcription factor Nrf2.
Introduction of active ingredients in the medicinal juice of concoction auxiliariesRhizoma Dioscoreae Bulbiferae concocted with the juice of Glycyrrhizae Radix et RhizomaInter-ingredient detoxificationLiquiritinGlycyrrhizic acidDiosbulbin B
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