Temporal changes of hepatic drug-metabolizing enzymes mediated by hepatic ischemia-reperfusion injury and the protective effect of Oridonin
Abstract Hepatic ischemia-reperfusion injury (IRI) is a common complication associated with metabolic disturbances and postoperative liver failure. Despite its prevalence, there is still a significant gap in understanding the changes in hepatic drug-metabolizing enzymes—specifically cytochrome P450s...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-06179-3 |
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| author | Tanwei Gu Fahong Dai Meiqun Cai Xi Zhang Danni Xie Huanguo Jiang Lingmin Tian Liyan Yan Wenxun Lan Haitao Lv Lan Tang Hong Li Zhaoguo Liu |
| author_facet | Tanwei Gu Fahong Dai Meiqun Cai Xi Zhang Danni Xie Huanguo Jiang Lingmin Tian Liyan Yan Wenxun Lan Haitao Lv Lan Tang Hong Li Zhaoguo Liu |
| author_sort | Tanwei Gu |
| collection | DOAJ |
| description | Abstract Hepatic ischemia-reperfusion injury (IRI) is a common complication associated with metabolic disturbances and postoperative liver failure. Despite its prevalence, there is still a significant gap in understanding the changes in hepatic drug-metabolizing enzymes—specifically cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs)—that occur due to hepatic IRI and in identifying effective treatment strategies. This study highlights the temporal changes in the expression and activity of CYPs and UGTs mediated by hepatic ischemia-reperfusion injury, demonstrating a correlation between these enzymatic changes and indicators of liver injury. Our findings demonstrate that Oridonin (ORI), a natural monomer derived from the traditional Chinese medicinal herb Rabdosia rubescens, has notable anti-inflammatory and antioxidant properties. ORI was found to counteract the adverse effects of hepatic IRI on CYPs and UGTs, thus alleviating the metabolic disturbances associated with the injury. Moreover, ORI effectively inhibits inflammatory responses, oxidative stress, and apoptosis related to hepatic IRI. It does this by suppressing the NLRP3 inflammatory pathway, activating the Nrf2 endogenous antioxidant pathway, and modulating the levels of key proteins such as Bcl-2. ORI also demonstrated efficacy in reducing inflammation in a cell hypoxia/reoxygenation (H/R) model. These results suggest that ORI holds promise as a therapeutic candidate for the treatment of hepatic IRI. |
| format | Article |
| id | doaj-art-d7dd14a648fe43bdbc26feaf2ae33fa7 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
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| spelling | doaj-art-d7dd14a648fe43bdbc26feaf2ae33fa72025-08-20T03:04:25ZengNature PortfolioScientific Reports2045-23222025-08-0115111310.1038/s41598-025-06179-3Temporal changes of hepatic drug-metabolizing enzymes mediated by hepatic ischemia-reperfusion injury and the protective effect of OridoninTanwei Gu0Fahong Dai1Meiqun Cai2Xi Zhang3Danni Xie4Huanguo Jiang5Lingmin Tian6Liyan Yan7Wenxun Lan8Haitao Lv9Lan Tang10Hong Li11Zhaoguo Liu12Department of Infectious Diseases, Shunde Hospital, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversitySchool of Chinese Medicine, State Key Laboratory of Environmental and Biological Analysis, Hong Kong Chinese Medicine Phenome Research Center, Hong Kong Baptist UniversityDepartment of Infectious Diseases, Shunde Hospital, Southern Medical UniversityDepartment of Infectious Diseases, Shunde Hospital, Southern Medical UniversityNMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical UniversityAbstract Hepatic ischemia-reperfusion injury (IRI) is a common complication associated with metabolic disturbances and postoperative liver failure. Despite its prevalence, there is still a significant gap in understanding the changes in hepatic drug-metabolizing enzymes—specifically cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs)—that occur due to hepatic IRI and in identifying effective treatment strategies. This study highlights the temporal changes in the expression and activity of CYPs and UGTs mediated by hepatic ischemia-reperfusion injury, demonstrating a correlation between these enzymatic changes and indicators of liver injury. Our findings demonstrate that Oridonin (ORI), a natural monomer derived from the traditional Chinese medicinal herb Rabdosia rubescens, has notable anti-inflammatory and antioxidant properties. ORI was found to counteract the adverse effects of hepatic IRI on CYPs and UGTs, thus alleviating the metabolic disturbances associated with the injury. Moreover, ORI effectively inhibits inflammatory responses, oxidative stress, and apoptosis related to hepatic IRI. It does this by suppressing the NLRP3 inflammatory pathway, activating the Nrf2 endogenous antioxidant pathway, and modulating the levels of key proteins such as Bcl-2. ORI also demonstrated efficacy in reducing inflammation in a cell hypoxia/reoxygenation (H/R) model. These results suggest that ORI holds promise as a therapeutic candidate for the treatment of hepatic IRI.https://doi.org/10.1038/s41598-025-06179-3OridoninHepatic ischemia-reperfusion injuryCYPs/UGTsTemporal changesOxidative stress |
| spellingShingle | Tanwei Gu Fahong Dai Meiqun Cai Xi Zhang Danni Xie Huanguo Jiang Lingmin Tian Liyan Yan Wenxun Lan Haitao Lv Lan Tang Hong Li Zhaoguo Liu Temporal changes of hepatic drug-metabolizing enzymes mediated by hepatic ischemia-reperfusion injury and the protective effect of Oridonin Scientific Reports Oridonin Hepatic ischemia-reperfusion injury CYPs/UGTs Temporal changes Oxidative stress |
| title | Temporal changes of hepatic drug-metabolizing enzymes mediated by hepatic ischemia-reperfusion injury and the protective effect of Oridonin |
| title_full | Temporal changes of hepatic drug-metabolizing enzymes mediated by hepatic ischemia-reperfusion injury and the protective effect of Oridonin |
| title_fullStr | Temporal changes of hepatic drug-metabolizing enzymes mediated by hepatic ischemia-reperfusion injury and the protective effect of Oridonin |
| title_full_unstemmed | Temporal changes of hepatic drug-metabolizing enzymes mediated by hepatic ischemia-reperfusion injury and the protective effect of Oridonin |
| title_short | Temporal changes of hepatic drug-metabolizing enzymes mediated by hepatic ischemia-reperfusion injury and the protective effect of Oridonin |
| title_sort | temporal changes of hepatic drug metabolizing enzymes mediated by hepatic ischemia reperfusion injury and the protective effect of oridonin |
| topic | Oridonin Hepatic ischemia-reperfusion injury CYPs/UGTs Temporal changes Oxidative stress |
| url | https://doi.org/10.1038/s41598-025-06179-3 |
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