Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice
Cyclophosphamide (CTX) is a chemotherapeutic agent with cytotoxic and immunosuppressive activity. It is used to treat a wide variety of cancers and autoimmune diseases. However, side effects caused by its toxic metabolites, especially hepatotoxicity, limit its clinical application. The natural dihyd...
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Elsevier
2025-12-01
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| author | Fei Teng Haina Wang |
| author_facet | Fei Teng Haina Wang |
| author_sort | Fei Teng |
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| description | Cyclophosphamide (CTX) is a chemotherapeutic agent with cytotoxic and immunosuppressive activity. It is used to treat a wide variety of cancers and autoimmune diseases. However, side effects caused by its toxic metabolites, especially hepatotoxicity, limit its clinical application. The natural dihydroflavonol compound dihydromyricetin (DHM) has anticancer, anti-inflammatory, and antioxidant properties. This study aimed to evaluate the protective effects of DHM against CTX-induced hepatotoxicity in mice. Male ICR mice were pretreated with DHM (100, 200, and 400 mg/kg b.w.) orally before intraperitoneal injection with CTX (100 mg/kg b.w.) for 7 days. The mice were then sacrificed to analyze biochemical and histological parameters as well as metabolomics profiles. DHM ameliorated CTX-induced elevations in the liver index, alanine aminotransferase, aspartate transaminase, and malondialdehyde levels, and pathological changes and increased levels of glutathione and antioxidant enzymes, such as superoxide dismutase and catalase. Based on a KEGG pathway analysis of altered serum and liver metabolites, OXPHOS may play an important role in the observed protective effects. Further analysis revealed that DHM increased the activity of Na+-K+-ATPase in mice, which affected CTX-induced mitochondrial energy metabolism. To conclude, DHM protected against CTX-induced hepatotoxicity, possibly through reducing oxidative stress and regulating energy metabolism, providing a potential strategy for treatment and prevention. |
| format | Article |
| id | doaj-art-95b44040926c4efd9661b2ef15b2b7e2 |
| institution | DOAJ |
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| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
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| series | Pharmaceutical Science Advances |
| spelling | doaj-art-95b44040926c4efd9661b2ef15b2b7e22025-08-20T03:00:50ZengElsevierPharmaceutical Science Advances2773-21692025-12-01310006310.1016/j.pscia.2025.100063Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in miceFei Teng0Haina Wang1School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR ChinaCorresponding author.; School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR ChinaCyclophosphamide (CTX) is a chemotherapeutic agent with cytotoxic and immunosuppressive activity. It is used to treat a wide variety of cancers and autoimmune diseases. However, side effects caused by its toxic metabolites, especially hepatotoxicity, limit its clinical application. The natural dihydroflavonol compound dihydromyricetin (DHM) has anticancer, anti-inflammatory, and antioxidant properties. This study aimed to evaluate the protective effects of DHM against CTX-induced hepatotoxicity in mice. Male ICR mice were pretreated with DHM (100, 200, and 400 mg/kg b.w.) orally before intraperitoneal injection with CTX (100 mg/kg b.w.) for 7 days. The mice were then sacrificed to analyze biochemical and histological parameters as well as metabolomics profiles. DHM ameliorated CTX-induced elevations in the liver index, alanine aminotransferase, aspartate transaminase, and malondialdehyde levels, and pathological changes and increased levels of glutathione and antioxidant enzymes, such as superoxide dismutase and catalase. Based on a KEGG pathway analysis of altered serum and liver metabolites, OXPHOS may play an important role in the observed protective effects. Further analysis revealed that DHM increased the activity of Na+-K+-ATPase in mice, which affected CTX-induced mitochondrial energy metabolism. To conclude, DHM protected against CTX-induced hepatotoxicity, possibly through reducing oxidative stress and regulating energy metabolism, providing a potential strategy for treatment and prevention.http://www.sciencedirect.com/science/article/pii/S2773216925000017DihydromyricetinCyclophosphamideHepatotoxicityMetabolomics |
| spellingShingle | Fei Teng Haina Wang Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice Pharmaceutical Science Advances Dihydromyricetin Cyclophosphamide Hepatotoxicity Metabolomics |
| title | Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice |
| title_full | Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice |
| title_fullStr | Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice |
| title_full_unstemmed | Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice |
| title_short | Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice |
| title_sort | protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide induced hepatotoxicity in mice |
| topic | Dihydromyricetin Cyclophosphamide Hepatotoxicity Metabolomics |
| url | http://www.sciencedirect.com/science/article/pii/S2773216925000017 |
| work_keys_str_mv | AT feiteng protectiveeffectsandmetabolomicsanalysisofdihydromyricetinoncyclophosphamideinducedhepatotoxicityinmice AT hainawang protectiveeffectsandmetabolomicsanalysisofdihydromyricetinoncyclophosphamideinducedhepatotoxicityinmice |