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桦褐孔菌提取物通过 PI3K/Akt 和 AMPK/ACC 通路对小鼠糖脂代谢的调节作用。

Effect of Inonotus obliquus (Fr.) Pilat extract on the regulation of glycolipid metabolism via PI3K/Akt and AMPK/ACC pathways in mice.

机构信息

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China.

College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China.

出版信息

J Ethnopharmacol. 2021 Jun 12;273:113963. doi: 10.1016/j.jep.2021.113963. Epub 2021 Feb 26.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Inonotus obliquus (Fr.) Pilat is a mushroom belonging to the family Hymenochaetaceae. It is popularly called the Chaga mushroom in Russian folk medicine and has been used as a traditional medicine to treat diabetes mellitus in Eastern European and Asian countries. However, its effects on glycolipid metabolism disorders and underlying molecular mechanism of action remain unclear.

AIM OF THE STUDY

I. obliquus contains abundant functional components, which provide potential medicinal value. The purpose of this study was to investigate compositions of I. obliquus extract with a high-pressure water extraction method, and investigate the anti-type 2 diabetic effects of I. obliquus extract and the possible underlying mechanisms involved.

MATERIALS AND METHODS

The I. obliquus was extracted by a high-pressure water extraction method, and tested its main components by special assay kit and instrumental analysis. Type 2 diabetic C57BL/6 mice were induced by high-fat diet with low-dose STZ injection, and were daily gavaged with different doses of I. obliquus extract for 8 weeks. Glycemic, blood lipid profile, and histopathology of liver and pancreas were assessed. Underlying mechanisms related to glycemic control in liver were further performed.

RESULTS

The I. obliquus extract main compounds were β-Glucans, triterpenoids and polyphenol by determination. Oral administration of 250 mg/kg and 500 mg/kg I. obliquus extract significantly alleviated blood glucose and insulin resistance. Moreover, 250 mg/kg and 500 mg/kg of I. obliquus extract increased liver glycogen content and high-density lipoprotein cholesterol (HDL-C) levels while decreased total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels. Furthermore, the protein expression levels of phosphatidylinositol-3 kinase (PI3K), p-protein kinase B (Akt), p-adenosine monophosphate activated protein kinase (AMPK), and p-acetyl-CoA carboxylase (ACC) were upregulated, whereas sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) were downregulated after supplement with 250 mg/kg and 500 mg/kg of I. obliquus extract. Interestingly, I. obliquus extract was a dose-effect relationship within a certain range. 250 mg/kg had obvious anti-diabetes effect, and the effect of 500 mg/kg dose was the same as that of metformin.

CONCLUSION

I. obliquus extract ameliorated insulin resistance and lipid metabolism disorders in diabetic mice. The hypoglycemic and hypolipidemic properties of I. obliquus extract were supposedly exerted via the regulation of the PI3K/Akt and AMPK/ACC signaling pathways.

摘要

民族药理学相关性

桦褐孔菌(Fr.)Pilat 是一种属于 Hymenochaetaceae 科的蘑菇。在俄罗斯民间医学中,它通常被称为桦褐孔菌,已被用作治疗东欧和亚洲国家糖尿病的传统药物。然而,其对糖脂代谢紊乱的影响及其潜在的作用机制尚不清楚。

研究目的

桦褐孔菌含有丰富的功能成分,具有潜在的药用价值。本研究的目的是采用高压水提法提取桦褐孔菌提取物,并研究桦褐孔菌提取物的抗 2 型糖尿病作用及其可能涉及的潜在机制。

材料和方法

采用高压水提法提取桦褐孔菌,并用特殊试剂盒和仪器分析测试其主要成分。采用高脂饮食联合低剂量 STZ 注射诱导 2 型糖尿病 C57BL/6 小鼠,每日灌胃不同剂量的桦褐孔菌提取物 8 周。评估血糖、血脂谱以及肝和胰腺的组织病理学。进一步研究与肝脏血糖控制相关的潜在机制。

结果

通过测定,桦褐孔菌提取物的主要化合物为β-葡聚糖、三萜类化合物和多酚。250mg/kg 和 500mg/kg 的桦褐孔菌提取物可显著改善血糖和胰岛素抵抗。此外,250mg/kg 和 500mg/kg 的桦褐孔菌提取物可增加肝糖原含量和高密度脂蛋白胆固醇(HDL-C)水平,同时降低总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平。此外,补充 250mg/kg 和 500mg/kg 的桦褐孔菌提取物可上调磷酸肌醇-3 激酶(PI3K)、蛋白激酶 B(Akt)、腺苷单磷酸激活蛋白激酶(AMPK)和乙酰辅酶 A 羧化酶(ACC)的蛋白表达水平,而固醇调节元件结合蛋白-1c(SREBP-1c)和脂肪酸合酶(FAS)的蛋白表达水平则下调。有趣的是,桦褐孔菌提取物在一定范围内呈剂量效应关系。250mg/kg 剂量具有明显的抗糖尿病作用,而 500mg/kg 剂量的作用与二甲双胍相同。

结论

桦褐孔菌提取物可改善糖尿病小鼠的胰岛素抵抗和脂代谢紊乱。桦褐孔菌提取物的降血糖和降血脂作用可能是通过调节 PI3K/Akt 和 AMPK/ACC 信号通路发挥的。

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