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Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase

引用

Journal of Pharmaceutical Analysis 2023年第6期13卷 640-659页

作者： Congcong Chen Wenxia Gong junshen tian Xiaoxia Gao Xuemei Qin Guanhua Du Yuzhi Zhou Modern Research Center for Traditional Chinese Medicine The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of EducationShanxi UniversityTaiyuan030006China Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province Shanxi UniversityTaiyuan030006China Institute of Materia Medica Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm *** many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb ***,whether RPA can alleviate RB-induced hepatotoxicity remain *** this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused ***,RPA effectively reversed RB-induced ***,the mechanism of RB-induced hepatotoxicity was *** results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)***,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were *** results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in *** from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding *** on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 *** conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

关键词： Radix Bupleuri Radix Paeoniae Alba Hepatotoxicity Gut microbiota Saikosaponins Combination mechanisms

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