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

Congcong Chen; Wenxia Gong; Junshen Tian; Xiaoxia Gao; Xuemei Qin; Guanhua Du; Yuzhi Zhou

doi:10.1016/j.jpha.2023.04.016

Volume 13 Issue 6

Jun. 2023

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Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(6): 640-659

Congcong Chen, Wenxia Gong, Junshen Tian, Xiaoxia Gao, Xuemei Qin, Guanhua Du, Yuzhi Zhou. Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase[J]. Journal of Pharmaceutical Analysis, 2023, 13(6): 640-659. doi: 10.1016/j.jpha.2023.04.016

Citation:

Congcong Chen, Wenxia Gong, Junshen Tian, Xiaoxia Gao, Xuemei Qin, Guanhua Du, Yuzhi Zhou. Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase[J]. Journal of Pharmaceutical Analysis, 2023, 13(6): 640-659. doi: 10.1016/j.jpha.2023.04.016

Citation:

Congcong Chen, Wenxia Gong, Junshen Tian, Xiaoxia Gao, Xuemei Qin, Guanhua Du, Yuzhi Zhou. Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase[J]. Journal of Pharmaceutical Analysis, 2023, 13(6): 640-659. doi: 10.1016/j.jpha.2023.04.016

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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

doi: 10.1016/j.jpha.2023.04.016

Congcong Chen^a,b,
Wenxia Gong^a,b,
Junshen Tian^a,b,
Xiaoxia Gao^a,b,
Xuemei Qin^a,b,
Guanhua Du^a,c,
Yuzhi Zhou^{a,b
,
,}

a. 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;
b. Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, 030006, China;
c. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China

Funds:

This study is funded by the National Nature Science Foundation of China (Grant Nos.: 82074323, and 81673572). Key Research and Development Program of Shanxi Province (Program No.: 202102130501010). The major science and technology project for “Significant New Drugs Creation” (Project No.: 2017ZX09301047). Research Project Supported by Shanxi Scholarship Council of China (Project No.: 2020019). The special fund for Science and Technology Innovation Teams of Shanxi Province (Grant No.: 202204051002011).

Received Date: Jan. 12, 2023
Accepted Date: Apr. 23, 2023
Rev Recd Date: Apr. 07, 2023
Publish Date: Apr. 26, 2023

Abstract

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 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-κB)/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 saikogenins 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 saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.
- Radix Bupleuri,
- Radix Paeoniae Alba,
- Hepatotoxicity,
- Gut microbiota,
- Saikosaponins,
- Combination mechanisms

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References(45)

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