Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway: Network pharmacology and experimental validation

小桶 安普克 PI3K/AKT/mTOR通路 蛋白激酶B 药理学 生物 信号转导 化学 激酶 蛋白激酶A 生物化学 转录组 基因表达 基因
作者
Ting Zhang,Qing Zhang,Wei Zheng,Ting Tao,Ruo-lan Li,Liyu Wang,Wei Peng,Chunjie Wu
出处
期刊:Journal of Integrative Medicine [Elsevier]
卷期号:20 (6): 543-560 被引量:9
标识
DOI:10.1016/j.joim.2022.07.004
摘要

This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli (FZ) against type 2 diabetes mellitus (T2DM) based on network pharmacology and experimental validation.Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry, and gas chromatography-mass spectrometry were used to identify the constituents of FZ. Next, the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases (including Gene Expression Omnibus database and Swiss Target Prediction online database), and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the pathway was verified by in vitro experiments, and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM.A total of 43 components were identified from FZ, and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM. The dug component-target network indicated that PPARA, PPARG, PIK3R3, JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM. Interestingly, the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in HepG2 cells. Moreover, FZ treatment was able to promote the AMPK and PI3K/Akt expressions in HepG2 cells.Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.
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