Division of Food and Nutrition, Chonnam National University, Gwangju 61186, Republic of Korea.
Department of Food and Nutrition, The University of Suwon, Hwaseong 18323, Republic of Korea.
Nutrients. 2022 Dec 18;14(24):5379. doi: 10.3390/nu14245379.
R. Br. (SP), grown from autumn to spring, is used as a medicinal herb from roots to leaves. This herb exhibits antioxidant activities and various physiological effect, including anti-asthma, immune-promoting, anti-obesity, and anti-cholesterol effects. However, the effectiveness of SP against non-alcoholic fatty liver disease (NAFLD) and the associated mechanism have not been elucidated. In this study, alleviation of NAFLD by SP was confirmed in a mouse model of hepatic steatosis induced by a high-fat diet and in HepG2 cells administered free fatty acids (FFA). In the experimental model, intrahepatic lipid accumulation was investigated using the AdipoRed assay, Oil Red O staining, biomarker analysis, and hematoxylin and eosin staining. Furthermore, glucose tolerance was examined based on the fasting glucose levels and oral glucose tolerance. The molecular mechanisms related to hepatic steatosis were determined based on marker mRNA levels. Blood FFAs were found to flow into the liver via the action of fatty acid translocase, cluster of differentiation 36, and fatty acid transporter proteins 2 and 5. R. Br. water extract (SPW) suppressed the FFAs inflow by regulating the expression of the above-mentioned proteins. Notably, modulating the expression of AMP-activated protein kinase (AMPK) and liver X receptor, which are involved in the regulation of lipid metabolism, stimulated peroxisome proliferator activated receptor α in the nucleus to induce the expression genes involved in β-oxidation and increase β-oxidation in the mitochondria. AMPK modulation also increased the expression of sterol regulatory element binding protein-1c, which activated lipid synthesis enzymes. As a consequence of these events, triglyceride synthesis was reduced and lipid accumulation in hepatocytes was alleviated. Overall, our findings suggested that SPW could ameliorate NAFLD by inhibiting hepatic steatosis through AMPK modulation.
山菅从秋季到春季生长，其根到叶皆可作为药用。该草药具有抗氧化活性和多种生理作用，包括抗哮喘、免疫促进、抗肥胖和降胆固醇作用。然而，SP 对非酒精性脂肪性肝病（NAFLD）的有效性及其相关机制尚未阐明。在本研究中，通过高脂肪饮食诱导的肝脂肪变性小鼠模型和给予游离脂肪酸（FFA）的 HepG2 细胞证实了 SP 对 NAFLD 的缓解作用。在实验模型中，使用 AdipoRed 测定法、油红 O 染色、生物标志物分析和苏木精和伊红染色研究肝内脂质积累。此外，根据空腹血糖水平和口服葡萄糖耐量试验检查葡萄糖耐量。根据标记物 mRNA 水平确定与肝脂肪变性相关的分子机制。发现血液 FFAs 通过脂肪酸易位酶、分化群 36、脂肪酸转运蛋白 2 和 5 的作用流入肝脏。R. Br. 水提取物（SPW）通过调节上述蛋白的表达抑制 FFAs 的流入。值得注意的是，调节参与脂质代谢调节的 AMP 激活蛋白激酶（AMPK）和肝 X 受体的表达，刺激核中的过氧化物酶体增殖物激活受体 α，诱导β-氧化相关基因的表达，并增加线粒体中的β-氧化。AMPK 调节还增加了固醇调节元件结合蛋白-1c 的表达，激活了脂质合成酶。因此，甘油三酯的合成减少，肝细胞内的脂质积累得到缓解。总的来说，我们的研究结果表明，SPW 可能通过调节 AMPK 来抑制肝脂肪变性从而改善 NAFLD。
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