NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2022, Vol. 34 ›› Issue (12): 2119-2129.doi: 10.16333/j.1001-6880.2022.12.016

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Study on the mechanism of Huangqisan in treating Alzheimer′s disease based on network pharmacology and experimental verification

ZHANG Yun-hui 1,2,YANG Meng-lin 1,2*,ZHOU Xiao-qing 2,WU Da-hua2,3,LIU Xia1,LI Xiang1   

  1. 1Chongqing Three Gorges Medical College,Chongqing 404120,China;2Hunan University of Chinese Medicine,Changsha 410208,China;3Affiliated Hospital of Hunan Provincial Academy of Traditional Chinese Medicine,Changsha 410006,China
  • Online:2022-12-28 Published:2022-12-29

Abstract:

To study the mechanism of Huangqisan in treating Alzheimer′s disease(AD) by network pharmacology.To search the active ingredients and corresponding targets of Huangqisan through the TCMSP databases,Then obtained the targets of AD through the DisGeNET and GeneCards database.Constructed protein interaction network map by String online database.At the same time GO and KEGG enrichment analysis of key targets were carried out by using R language.Induction of PC12 cell injury by adopted Aβ25-35 as AD cell model.Detection of cell viability by MTT assay.Observation of cell morphology and synaptic growth by microscope.Observation of Autophagosomes in PC12 cells by transmission electron microscopy.Detection of reactive oxygen species (ROS) content by using Kits.Finally,ELISA and Western blot were used to verify the main biological processes and signaling pathways predicted by network pharmacology.A total of 44 active ingredients of Huangqisan were screened,134 corresponding targets,102 targets related to Alzheimer′s disease.The top 20 KEGG related signaling pathways and GO analysis of the top 20 biological processes.Cell experiments proved that Huangqisan effectively increased the survival rate and synaptic length of PC12 cells,effectively promoted Aβ25-35 induced PC12 cells autophagosome wrapped damaged mitochondria,reduced the content of inflammatory factors IL-1β,IL-18,TNF-α,reduced ROS level,increased LC3 II/I ratio,up-regulated PINK1,parkin,BDNF protein expression,down-regulated p62,NLRP3 protein expression.Huangqisan had a therapeutic effect on AD by activated PINK1/parkin pathway to promoted mitophagy and reduced ROS levels,thereby inhibited the activation of NLRP3 inflammasome and improved synaptic plasticity.

Key words: Huangqisan, network pharmacology, Alzheimer′s disease, mitophagy

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