Shanghai Key Laboratory of Compound Chinese Medicines and The Ministry of Education Key Laboratory of Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
Mol Med Rep. 2018 Jan;17(1):1863-1872. doi: 10.3892/mmr.2017.8051. Epub 2017 Nov 14.
Cholestasis is defined as a functional impairment of bile secretion which results in the accumulation of bile acids (BAs) and other toxic molecules in the blood and liver, however, there are very few effective therapies for cholestasis. The farnesoid X receptor (FXR), as a nuclear receptor for BAs, is important in the regulation of BA levels in enterohepatic circulation. It has previously been demonstrated that activation of the FXR pathway may be a useful strategy with which to treat cholestasis. Resveratrol, one of the important ingredients from grape skins and Chinese medicine Polygonum cuspidatum, resulted in FXR‑activated effects in vitro and exhibited a protective effect against α‑naphthylisothiocyanate (ANIT)‑induced cholestasis through FXR regulation in vivo. The underlying mechanisms of resveratrol against ANIT‑induced cholestasis may be due to the regulation of BA homeostasis, improvement of liver injury and attenuation of the inflammatory response, which were regulated in a FXR‑dependent manner and in turn contributed to overall cholestasis alleviation. Overall, resveratrol as a FXR agonist may act as a potential compound for the treatment of drug‑induced cholestasis.
胆汁淤积症被定义为胆汁分泌功能障碍，导致胆汁酸（BAs）和其他有毒分子在血液和肝脏中积聚，但目前针对胆汁淤积症的有效治疗方法非常有限。法尼醇 X 受体（FXR）作为 BAs 的核受体，在调节肠肝循环中的 BA 水平方面非常重要。先前已经证明，激活 FXR 途径可能是治疗胆汁淤积症的一种有用策略。白藜芦醇是葡萄皮和中药虎杖中的重要成分之一，它在体外表现出 FXR 激活作用，并通过体内 FXR 调节表现出对α-萘异硫氰酸酯（ANIT）诱导的胆汁淤积的保护作用。白藜芦醇对抗 ANIT 诱导的胆汁淤积的潜在机制可能是通过调节 BA 动态平衡、改善肝损伤和减轻炎症反应来实现的，这些作用都是通过 FXR 依赖性调节的，从而有助于整体缓解胆汁淤积症。总的来说，作为 FXR 激动剂的白藜芦醇可能是治疗药物诱导的胆汁淤积症的一种潜在化合物。
