Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase
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 re...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-06-01
|
| Series: | Journal of Pharmaceutical Analysis |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177923000837 |
| _version_ | 1797790077141647360 |
|---|---|
| author | Congcong Chen Wenxia Gong Junshen Tian Xiaoxia Gao Xuemei Qin Guanhua Du Yuzhi Zhou |
| author_facet | Congcong Chen Wenxia Gong Junshen Tian Xiaoxia Gao Xuemei Qin Guanhua Du Yuzhi Zhou |
| author_sort | Congcong Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T01:59:37Z |
| format | Article |
| id | doaj.art-b03dc8a8bfd24f1baf084f485fa1becc |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-03-13T01:59:37Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-b03dc8a8bfd24f1baf084f485fa1becc2023-07-02T04:16:33ZengElsevierJournal of Pharmaceutical Analysis2095-17792023-06-01136640659Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetaseCongcong Chen0Wenxia Gong1Junshen Tian2Xiaoxia Gao3Xuemei Qin4Guanhua Du5Yuzhi Zhou6Modern 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, ChinaModern 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, ChinaModern 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, ChinaModern 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, ChinaModern 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, ChinaModern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, 030006, China; Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, ChinaModern 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; Corresponding author. 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.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.http://www.sciencedirect.com/science/article/pii/S2095177923000837Radix BupleuriRadix Paeoniae AlbaHepatotoxicityGut microbiotaSaikosaponinsCombination mechanisms |
| spellingShingle | 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 Journal of Pharmaceutical Analysis Radix Bupleuri Radix Paeoniae Alba Hepatotoxicity Gut microbiota Saikosaponins Combination mechanisms |
| title | Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase |
| title_full | Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase |
| title_fullStr | Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase |
| title_full_unstemmed | Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase |
| title_short | Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase |
| title_sort | radix paeoniae alba attenuates radix bupleuri induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase |
| topic | Radix Bupleuri Radix Paeoniae Alba Hepatotoxicity Gut microbiota Saikosaponins Combination mechanisms |
| url | http://www.sciencedirect.com/science/article/pii/S2095177923000837 |
| work_keys_str_mv | AT congcongchen radixpaeoniaealbaattenuatesradixbupleuriinducedhepatotoxicitybymodulatinggutmicrobiotatoalleviatetheinhibitionofsaikosaponinsonglutathionesynthetase AT wenxiagong radixpaeoniaealbaattenuatesradixbupleuriinducedhepatotoxicitybymodulatinggutmicrobiotatoalleviatetheinhibitionofsaikosaponinsonglutathionesynthetase AT junshentian radixpaeoniaealbaattenuatesradixbupleuriinducedhepatotoxicitybymodulatinggutmicrobiotatoalleviatetheinhibitionofsaikosaponinsonglutathionesynthetase AT xiaoxiagao radixpaeoniaealbaattenuatesradixbupleuriinducedhepatotoxicitybymodulatinggutmicrobiotatoalleviatetheinhibitionofsaikosaponinsonglutathionesynthetase AT xuemeiqin radixpaeoniaealbaattenuatesradixbupleuriinducedhepatotoxicitybymodulatinggutmicrobiotatoalleviatetheinhibitionofsaikosaponinsonglutathionesynthetase AT guanhuadu radixpaeoniaealbaattenuatesradixbupleuriinducedhepatotoxicitybymodulatinggutmicrobiotatoalleviatetheinhibitionofsaikosaponinsonglutathionesynthetase AT yuzhizhou radixpaeoniaealbaattenuatesradixbupleuriinducedhepatotoxicitybymodulatinggutmicrobiotatoalleviatetheinhibitionofsaikosaponinsonglutathionesynthetase |