经甘草药汁炮制引入的主要活性成分助力黄药子的减毒作用及其机制研究  

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

作　　者：宋玲玲 王君明[1,2,3] 段雅倩 纪丽婕 何庆文 张天柱 王彦嵋 巫晓慧 SONG Lingling;WANG Junming;DUAN Yaqian;JI Lijie;HE Qingwen;ZHANG Tianzhu;WANG Yanmei;WU Xiaohui(College of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China;Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment&Chinese Medicine Development of Henan Province,Henan University of Chinese Medicine,Zhengzhou 450046,China;Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学药学院,郑州450046 [2]河南中医药大学呼吸疾病中医药防治省部共建协同创新中心,郑州450046 [3]豫药全产业链研发河南省协同创新中心,郑州450046

出　　处：《中华中医药杂志》2024年第5期2369-2376,共8页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：河南省重点研发与推广专项(省科技攻关)(No.182102310255)。

摘　　要：目的:探究经甘草药汁炮制引入的主要活性成分甘草苷(LQ)、甘草酸(GA)对黄药子毒性成分黄独素B(DB)诱导主要毒性肝毒性的减毒作用,并初探其机制。方法:在前期发现甘草药汁制法能够对黄药子主要毒性肝毒和止咳祛痰主要功效起到减毒增效作用且炮制减毒机制涉及引入炮制辅料药甘草汁的主要活性成分LQ和GA以及对DB含量的抑制的基础上,本研究进一步通过对DB与LQ和GA联用前后小鼠肝损伤敏感指标血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)以及肝组织病理的检测分析综合验证引入的主要活性成分LQ和GA对DB诱导的主要毒性肝毒的减毒作用。此外,围绕DB肝毒的主要机制炎症和氧化损伤,初探其减毒机制。结果:与正常组比较,DB给药致使小鼠血清ALT、AST、ALP水平均显著升高(P<0.01),肝细胞变性,并伴有炎性浸润及血管瘀血,磷酸化核转录因子κB(p-NF-κB)/环氧合酶2(COX-2)蛋白表达水平显著上调,肝磷酸化磷酯酰肌醇3激酶(p-PI3K)/蛋白激酶B(p-Akt)/核因子E2相关因子2(Nrf2)蛋白表达水平显著下调(P<0.01);而经LQ、GA干预均在不同程度上逆转了上述指标的异常(P<0.05,P<0.01)。值得注意的是,对ALT、AST水平的逆转程度分析,LQ比GA对DB诱导的肝毒性的减毒作用分别高3.3%和2.8%;对ALP水平分析,GA比LQ对DB诱导的肝毒性的减毒作用高7.1%;对炎症信号通路关键分子NF-κB、COX-2分析,LQ比GA对DB诱导肝脏炎症反应的抑制作用分别高3.2%和2.5%;对抗氧化信号通路核心分子Nrf2分析,GA比LQ对DB诱导肝脏抗氧化水平低下的上调作用高18.2%。结论:LQ和GA均能够对DB诱导的肝毒性起到减毒作用;减毒机制涉及抑制NF-κB/COX-2信号介导的肝脏炎症反应并增强转录因子Nrf2介导的抗氧化防御。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

关 键 词：药汁活性成分引入 甘草炮制黄药子 成分减毒 甘草苷 甘草酸 黄独素B 

分 类 号：R285.5[医药卫生—中药学]