Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key laboratory of Traditional Chinese Medicine, Shanghai 201203, China.
Biomed Pharmacother. 2019 May;113:108778. doi: 10.1016/j.biopha.2019.108778. Epub 2019 Mar 18.
Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide health problem, but no approved medical treatment exists so far. Nuclear receptors are one of the drug targets for nonalcoholic steatohepatitis (NASH). Among them, liver X receptor (LXR) has been studied in recent years in tumors, metabolic diseases and inflammatory diseases, but its physiological and pharmacological effects in the treatment of NASH are controversial. Activation of LXR has the potential to modulate cholesterol homeostasis, induce anti-inflammatory effects and increase insulin sensitivity, but liver lipid deposition and hypertriglyceridemia are also increased. Inhibition of liver LXR transcriptional activity in the context of NAFLD can effectively alleviate hepatic steatosis, inflammation, and fibrosis but elevates the risk of potential cardiovascular disease. The contradictory pharmacodynamic effects of LXR in the treatment of NASH increase the difficulty of developing targeted drugs. Moreover, natural compounds play an important part in drug development, and in recent years, some natural compounds have been reported to treat NAFLD by acting on LXR or LXR pathways with fewer adverse reactions, presenting a promising therapeutic prospect. In this review, we discuss the mechanisms of LXR in NASH and summarize the natural products reported to modulate NAFLD via LXR or the LXR pathway, offering an alternative approach for LXR-related drug development in NAFLD.
非酒精性脂肪性肝病（NAFLD）正在成为全球性的健康问题，但迄今为止尚无批准的医学治疗方法。核受体是治疗非酒精性脂肪性肝炎（NASH）的药物靶点之一。其中，肝 X 受体（LXR）近年来在肿瘤、代谢性疾病和炎症性疾病中得到了研究，但在治疗 NASH 中的生理和药理作用仍存在争议。激活 LXR 具有调节胆固醇稳态、诱导抗炎作用和增加胰岛素敏感性的潜力，但也会增加肝脏脂质沉积和高三酰甘油血症。在 NAFLD 背景下抑制肝 LXR 转录活性可有效减轻肝脂肪变性、炎症和纤维化，但会增加潜在心血管疾病的风险。LXR 在治疗 NASH 中的矛盾药效作用增加了开发靶向药物的难度。此外，天然化合物在药物开发中起着重要作用，近年来，一些天然化合物被报道通过作用于 LXR 或 LXR 通路来治疗 NAFLD，不良反应较少，呈现出有希望的治疗前景。在这篇综述中，我们讨论了 LXR 在 NASH 中的作用机制，并总结了报道的通过 LXR 或 LXR 通路调节 NAFLD 的天然产物，为 LXR 相关的 NAFLD 药物开发提供了一种替代方法。
