Metabolic activation and cytotoxicity of bavachin mediated by CYP3A in mice
文献类型：期刊论文
| 作者 | Ye, Tingmin4; Tang, Chunping2,3; Yang, Dandan4; Zhang, Qing4; Liao, Yufen4; Dai, Jie4; Tang, Hong4; Ke, Changqiang2,3; Peng, Ying1; Ye, Yang2,3 |
| 刊名 | CHEMICO-BIOLOGICAL INTERACTIONS
 |
| 出版日期 | 2025-10-08 |
| 卷号 | 419页码:10 |
| 关键词 | Bavachin metabolic activation Quinone Cytotoxicity Glutathione Psoraleae fructus |
| ISSN号 | 0009-2797 |
| DOI | 10.1016/j.cbi.2025.111630 |
| 通讯作者 | Peng, Ying(yingpeng1999@163.com) ; Ye, Yang(yye@simm.ac.cn) ; Li, Weiwei(weiweili0615@163.com) ; Zheng, Jiang(zhengjiang@syphu.edu.cn) |
| 英文摘要 | Bavachin (BVC), a flavonoid, is found in Psoraleae fructus (PF) which has been reported to induce various adverse effects, particularly hepatotoxicity, such as increases of serum alanine transaminase (ALT) and aspartate transaminase (AST) in mice given BVC. However, the mechanisms underlying its hepatotoxicity remain unclear. During the incubation of mouse microsomes with BVC in the presence of glutathione (GSH) or N-acetylcysteine (NAC), one oxidative metabolite (M1), one GSH conjugate (M2), and one NAC conjugate (M3) were observed. M1 was successfully synthesized by selective oxidation of BVC. Similar microsomal incubations of synthetic M1 offered M2 and M3. Following oral administration of BVC, the presence of biliary M2 and urinary M3 was observed in mice given BVC. CYP3A identified as the major enzyme was involved in the metabolic activation of BVC. The metabolic activation of BVC involved hydroxylation of BVC and sequential oxidation of the hydroxylation product to the corresponding o-quinone derivative. BVC treatment resulted in significant cytotoxicity in cultured mouse primary hepatocytes, and pretreatment with 1-aminobenzotriazole and ketoconazole decreased the susceptibility of hepatocytes to the cytotoxicity of BVC. Oral administration of PF extract resulted in a quick decline in hepatic GSH, along with the detection of GSH conjugate M2, in mice. BVC, a principal component of PF, was also found to deplete hepatic GSH in mice over a brief period. This evidence suggests that metabolic activation of BVC leads to depletion of GSH in vivo and that BVC contributes to the depletion of hepatic GSH caused by PF extract. |
| WOS关键词 | FRUCTUS-PSORALEAE ; COMPONENTS |
| 资助项目 | Guizhou Provincial Scientific and Technological Program[[2024] 015] ; Guizhou Science and Tech-nology Department[CXTD [2023] 019] ; Guizhou Science and Technology Department[ZK [2023] 319] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:001532812800003 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318852]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Peng, Ying; Ye, Yang; Li, Weiwei; Zheng, Jiang |
| 作者单位 | 1.Shenyang Pharmaceut Univ, Wuya Coll Innovat, POB 21,103 Wenhua Rd, Shenyang 110016, Liaoning, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Chem Dept, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Guizhou Med Univ, Engn Res Ctr Dev & Applicat Ethn Med & TCM, Guizhou Prov Engn Res Ctr Dev & Applicat Ethn Med, State Key Lab Discovery & Utilizat Funct Component, Guiyang 550004, Guizhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ye, Tingmin,Tang, Chunping,Yang, Dandan,et al. Metabolic activation and cytotoxicity of bavachin mediated by CYP3A in mice[J]. CHEMICO-BIOLOGICAL INTERACTIONS,2025,419:10. |
| APA | Ye, Tingmin.,Tang, Chunping.,Yang, Dandan.,Zhang, Qing.,Liao, Yufen.,...&Zheng, Jiang.(2025).Metabolic activation and cytotoxicity of bavachin mediated by CYP3A in mice.CHEMICO-BIOLOGICAL INTERACTIONS,419,10. |
| MLA | Ye, Tingmin,et al."Metabolic activation and cytotoxicity of bavachin mediated by CYP3A in mice".CHEMICO-BIOLOGICAL INTERACTIONS 419(2025):10. |
入库方式： OAI收割
来源：上海药物研究所
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