Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase
10.1016/j.jpha.2023.04.016
- Author:
Congcong CHEN
1
;
Wenxia GONG
;
Junshen TIAN
;
Xiaoxia GAO
;
Xuemei QIN
;
Guanhua DU
;
Yuzhi ZHOU
Author Information
1. Modern Research Center for Traditional Chinese Medicine,The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Shanxi University,Taiyuan,030006,China;Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province,Shanxi University,Taiyuan,030006,China
- Keywords:
Radix Bupleuri;
Radix Paeoniae Alba;
Hepatotoxicity;
Gut microbiota;
Saikosaponins;
Combination mechanisms
- From:
Journal of Pharmaceutical Analysis
2023;13(6):640-659
- CountryChina
- Language:Chinese
-
Abstract:
Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after long-term use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saiko-saponin 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)pathway.Furthermore,the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to sai-kogenins in vivo.Different 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 activity.Based 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 NF-κB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosa-ponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.
