The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China; Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; The First People's Hospital of Kashgar Prefecture, Kashgar, Xinjiang Uygur Autonomous Region, China; The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
J Ethnopharmacol. 2021 Oct 28;279:114340. doi: 10.1016/j.jep.2021.114340. Epub 2021 Jun 22.
BACKGROUND: Cassia mimosoides Linn (CMD) is a traditional Chinese herb that clears liver heat and dampness. It has been widely administered in clinical practice to treat jaundice associated with damp-heat pathogen and obesity. Emodin (EMO) is a major bioactive constituent of CMD that has apparent therapeutic efficacy against obesity and fatty liver. Here, we investigated the protective effects and underlying mechanisms of EMO against high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: We aimed to investigate whether EMO activates farnesoid X receptor (FXR) signaling to alleviate HFD-induced NAFLD. MATERIALS AND METHODS: In vivo assays included serum biochemical indices tests, histopathology, western blotting, and qRT-PCR to evaluate the effects of EMO on glucose and lipid metabolism disorders in wild type (WT) and FXR knockout mice maintained on an HFD. In vitro experiments included intracellular triglyceride (TG) level measurement and Oil Red O staining to assess the capacity of EMO to remove lipids induced by oleic acid and palmitic acid in WT and FXR knockout mouse primary hepatocytes (MPHs). We also detected mRNA expression of FXR signaling genes in MPHs. RESULTS: After HFD administration, body weight and serum lipid and inflammation levels were dramatically increased in the WT mice. The animals also presented with impaired glucose tolerance, insulin resistance, and antioxidant capacity, liver tissue attenuation, and pathological injury. EMO remarkably reversed the foregoing changes in HFD-induced mice. EMO improved HFD-induced lipid accumulation, insulin resistance, inflammation, and oxidative stress in a dose-dependent manner in WT mice by inhibiting FXR expression. EMO also significantly repressed TG hyperaccumulation by upregulating FXR expression in MPHs. However, it did not improve lipid accumulation, insulin sensitivity, or glucose tolerance in HFD-fed FXR knockout mice. CONCLUSIONS: The present study demonstrated that EMO alleviates HFD-induced NAFLD by activating FXR signaling which improves lipid accumulation, insulin resistance, inflammation, and oxidative stress.
背景：山芝麻（CMD）是一种传统的中药，具有清肝利湿的功效。它在临床上被广泛用于治疗湿热病邪引起的黄疸和肥胖症。大黄素（EMO）是 CMD 的主要生物活性成分，对肥胖症和脂肪肝具有明显的治疗作用。在这里，我们研究了 EMO 对高脂肪饮食（HFD）诱导的非酒精性脂肪性肝病（NAFLD）的保护作用及其潜在机制。
目的：本研究旨在探讨 EMO 是否通过激活法尼醇 X 受体（FXR）信号通路来减轻 HFD 诱导的 NAFLD。
材料和方法：体内实验包括血清生化指标检测、组织病理学、Western blot 和 qRT-PCR，以评估 EMO 对 HFD 喂养的野生型（WT）和 FXR 敲除小鼠葡萄糖和脂质代谢紊乱的影响。体外实验包括细胞内三酰甘油（TG）水平测定和油红 O 染色，以评估 EMO 去除油酸和软脂酸诱导的 WT 和 FXR 敲除小鼠原代肝细胞（MPHs）中脂质的能力。我们还检测了 MPHs 中 FXR 信号基因的 mRNA 表达。
结果：在 HFD 喂养后，WT 小鼠的体重和血清脂质及炎症水平显著升高。这些动物还出现葡萄糖耐量受损、胰岛素抵抗和抗氧化能力下降、肝组织衰减和病理损伤。EMO 显著逆转了 HFD 诱导的这些变化。EMO 通过抑制 FXR 表达，以剂量依赖性方式改善 HFD 诱导的小鼠的脂质积累、胰岛素抵抗、炎症和氧化应激。EMO 还通过上调 FXR 表达，显著抑制 MPHs 中的 TG 过度积累。然而，它并没有改善 HFD 喂养的 FXR 敲除小鼠的脂质积累、胰岛素敏感性或葡萄糖耐量。
结论：本研究表明，EMO 通过激活 FXR 信号减轻 HFD 诱导的 NAFLD，从而改善脂质积累、胰岛素抵抗、炎症和氧化应激。
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