基于AMPKα/SREBP-1/ACCα信号通路调节糖脂代谢的山楂果叶配伍机制

Compatibility mechanism of hawthorn fruit and leaf regulating glycolipid metabolism based on AMPKα/SREBP-1/ACCα pathway

糖脂代谢病是由遗传、环境和精神状况引起的一种复杂性疾病,其特点是糖、脂代谢紊乱,中医学称之为“消渴症”,随着生活水平和社会压力的提高该疾病呈现多龄化趋势。中药的多组分协同增效使其在长期治疗消渴症方面具有明显优势。山楂果、叶富含有机酸和黄酮类成分,在降糖降脂方面具有显著效果。测定了山楂果、叶提取物中主要成分的含量,建立了T2DM大鼠模型,研究了山楂果叶提取物干预AMPKα/SREBP-1/ACCα信号通路进而调节糖脂代谢的作用和机制,结合网络药理学方法分析山楂果、叶治疗T2DM的有效成分、作用靶点和作用机制。结果表明,山楂果、叶配伍给药能更显著降低T2DM大鼠空腹血糖血脂水平,提高糖耐量水平,促进胰岛素分泌,降低脂肪堆积,缩小脂肪细胞,同时调节肝肾功能,增加肝脏AMPKα及其磷酸化水平,降低SREBP-1、ACCα的蛋白表达。网络药理学共筛选到14个山楂果、叶的有效成分,与疾病交集靶点共150个,参与调控PI3K-Akt信号通路、MAPK信号通路、胰岛素抵抗等与糖脂代谢相关的多个信号通路。研究表明,山楂的果、叶配伍能够通过干预AMPKα/SREBP-1/ACCα通路,协同调节糖脂代谢,并且对于PI3k-Akt信号通路、MAPK信号通路、胰岛素抵抗等也有调节作用,具有良好的临床应用前景。

Glucolipid metabolic disease is a complex disease characterized by disorder of glucose and lipid metabolism and caused by genetic, environmental and mental conditions. It is called "Xiaoke disease" in traditional Chinese medicine. With the improvement of living standards and social pressure, it shows a multi-aging trend. The multi-component synergy of traditional Chinese medicine has obvious advantages in the long-term treatment of diabetes. Hawthorn fruit and leaves are rich in organic acids and flavonoids, which have significant effect on lowering blood sugar and blood lipids. In this study, the contents of the main components in hawthorn fruit and leaf extracts were determined, and the T2DM rat model was established to study the effect and mechanism of hawthorn fruit and leaf extracts on AMPKα/SREBP-1/ACCα signaling pathway and regulation of glucose and lipid metabolism. Combined with the method of network pharmacology, the effective components, action targets and action mechanism of hawthorn fruit and leaf in the treatment of T2DM were analyzed. The results showed that the combined administration of hawthorn fruit and leaf could significantly reduce the fasting blood glucose and lipid level, improve the glucose tolerance level, promote insulin secretion, reduce fat accumulation, shrink adipocytes, regulate liver and kidney function and increase AMPKα phosphorylation, reduce protein expression of SREBP-1 and ACCα. A total of 14 active components of hawthorn fruit leaves were screened by network pharmacology, with a total of 150 disease intersection targets, which are involved in the regulation of PI3K/Akt signaling pathway, MAPK signaling pathway, insulin resistance and other signaling pathways related to glucose and lipid metabolism. This study shows that the compatibility of fruit and leaf of hawthorn can regulate glucose and lipid metabolism through AMPKα-SREBP-1-ACCα pathway, which has a good prospect of clinical application.