Li Zhi-Jian, Abulizi Abudumijiti, Zhao Guo-Lin, Wang Tao, Zhou Fan, Jiang Zhen-Zhou, Aibai Silafu, Zhang Lu-Yong
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Department of Toxicology Laboratory Xinjiang Institute of Traditional Uyghur Medicine, Xinjiang Laboratory of Uyghur Medical Prescription, Urumqi, Xinjiang, 830049, China.
Phytother Res. 2017 Aug;31(8):1265-1272. doi: 10.1002/ptr.5851. Epub 2017 Jun 22.
Psoralea corylifolia L. (Fructus Psoraleae) is widely used in Asia, but there are concerns about hepatotoxicity caused by constituents such as psoralens and bakukiol. Bakuchiol (BAK) has antiinflammatory, antipyretic, antibacterial antiviral, anticancer, and estrogenic activity but appears to be hepatotoxic in in vitro tests. This study investigated the hepatotoxicity in vivo in rats. Using intragastrically administered bakuchiol at doses of 52.5 and 262.5 mg/kg for 6 weeks. Bodyweight, relative liver weight, biochemical indicators, histopathology, mRNA expression of CYP7A1, HMG-CoA reductase, BSEP, PPARα, SREBP-2, and MRP3 were measured. Many abnormalities were observed in the bakuchiol-treated groups including suppression of weight gain and food intake, change of some parameters in serum biochemistry, and increased weight of liver. The mRNA expression of CYP7A1, HMG-CoA reductase, PPARα, and SREBP-2 decreased in bakuchiol-treated group, the expression of BSEP increased in bakuchiol-treated low dosage, and the expression of BSEP decreased in bakuchiol-treated high dosage. In conclusion, we provide evidence for the first time that bakuchiol can induce cholestatic hepatotoxicity, suggesting potential hepatotoxicity. The mechanism may be related to effects on liver lipid metabolism, but further investigation is necessary. Copyright © 2017 John Wiley & Sons, Ltd.
补骨脂在亚洲被广泛使用，但人们担心补骨脂素和紫铆醇等成分会导致肝毒性。紫铆醇（BAK）具有抗炎、解热、抗菌、抗病毒、抗癌和雌激素活性，但在体外试验中似乎具有肝毒性。本研究调查了其在大鼠体内的肝毒性。以52.5和262.5毫克/千克的剂量通过胃内给药紫铆醇，持续6周。测量体重、相对肝脏重量、生化指标、组织病理学、CYP7A1、HMG-CoA还原酶、BSEP、PPARα、SREBP-2和MRP3的mRNA表达。在紫铆醇治疗组中观察到许多异常情况，包括体重增加和食物摄入量的抑制、血清生化中一些参数的变化以及肝脏重量增加。紫铆醇治疗组中CYP7A1、HMG-CoA还原酶、PPARα和SREBP-2的mRNA表达降低，紫铆醇低剂量治疗组中BSEP的表达增加，紫铆醇高剂量治疗组中BSEP的表达降低。总之，我们首次提供证据表明紫铆醇可诱导胆汁淤积性肝毒性，提示潜在的肝毒性。其机制可能与对肝脏脂质代谢的影响有关，但需要进一步研究。版权所有©2017约翰威立父子有限公司。
