Key Laboratory for Processing of Sugar Resources of Guangxi Higher Education Institutes, Guangxi University of Science and Technology, 268 Donghuan Road, Liuzhou, 545006, People's Republic of China.
Guangxi Key Laboratory of Green Processing of Sugar Resources, Guangxi University of Science and Technology, 268 Donghuan Road, Liuzhou, 545006, People's Republic of China.
BMC Complement Med Ther. 2023 Aug 16;23(1):288. doi: 10.1186/s12906-023-04110-9.
Non-alcoholic fatty liver disease (NAFLD) has been well defined as a common chronic liver metabolism disorder. Statins as a first-line therapeutic treatment had some side effects. Here, we found that Fumigaclavine C (FC) was collected from endophytic Aspergillus terreus via the root of Rhizophora stylosa (Rhizophoraceae), had potential anti-adipogenic and hepatoprotective effects both in vitro and in vivo without obvious adverse side effects. However, the mechanisms of the prevention and management of FC for hepatic steatosis are incompletely delineated.
The pharmacodynamic effects of FC were measured in high-fat diet (HFD)-induced obese mice. Liver index and blood biochemical were examined. Histopathological examination in the liver was performed by hematoxylin & eosin or oil red O. The levels of serum TG, TC, LDL-c, HDL-c, FFA, T-bili, ALT, AST, creatinine, and creatine kinase were estimated via diagnostic assay kits. The levels of hepatic lipid metabolism-related genes were detected via qRT-PCR. The expression levels of hepatic de novo lipogenesis were quantitated with Western blot analysis. RESULTS: FC-treatment markedly reduced hepatic lipid accumulation in HFD-induced obese mice. FC significantly attenuated the hepatic lipid metabolism and ameliorated liver injury without obvious adverse side effects. Moreover, FC also could dose-dependently modulate the expressions of lipid metabolism-related transcription genes. Mechanically, FC notably suppressed sterol response element binding protein-1c mediated de novo lipogenesis via interfering with the RhoA/ROCK signaling pathway by decreasing the levels of geranylgeranyl diphosphate and farnesyl diphosphate.
These findings suggested that FC could improve hepatic steatosis through inhibiting de novo lipogenesis via modulating the RhoA/ROCK signaling pathway.
非酒精性脂肪性肝病（NAFLD）已被明确为一种常见的慢性肝脏代谢紊乱。他汀类药物作为一线治疗药物有一些副作用。在这里，我们发现从内生曲霉属真菌通过红树科的根中分离得到的呋咱倍半萜 C（FC）具有潜在的抗脂肪生成和保肝作用，在体内外均无明显不良反应。然而，FC 预防和管理肝脂肪变性的机制尚未完全阐明。
在高脂饮食（HFD）诱导的肥胖小鼠中测定 FC 的药效学作用。检测肝指数和血液生化指标。通过苏木精和伊红或油红 O 对肝组织进行组织病理学检查。通过诊断试剂盒测定血清 TG、TC、LDL-c、HDL-c、FFA、T-bili、ALT、AST、肌酐和肌酸激酶水平。通过 qRT-PCR 检测肝脂质代谢相关基因水平。用 Western blot 分析定量检测肝从头合成的表达水平。
FC 治疗可显著减少 HFD 诱导的肥胖小鼠肝脏中的脂质堆积。FC 显著改善了肝脂质代谢和肝损伤，且无明显不良反应。此外，FC 还可以剂量依赖性地调节脂质代谢相关转录基因的表达。在机制上，FC 通过干扰 RhoA/ROCK 信号通路，显著抑制固醇反应元件结合蛋白-1c 介导的从头合成，从而降低 geranylgeranyl diphosphate 和 farnesyl diphosphate 的水平。
这些发现表明，FC 通过调节 RhoA/ROCK 信号通路抑制从头合成来改善肝脂肪变性。
