NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2023, Vol. 35 ›› Issue (5): 867-878. doi: 10.16333/j.1001-6880.2023.5.015

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Study on regulation of honokiol on HIF-1α-VEGF pathway in PC12 cells based on network pharmacology and experimental verification

FAN Xiao-xu1,TANG Qin1,YU Xue2,LI Li-na2,WANG Shu-yan2,CHANG Hong-sheng1*   

  1. 1School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;2School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China
  • Online:2023-05-26 Published:2023-05-26

Abstract:

To study the regulation of honokiol on the HIF-1α-VEGF pathway in PC12 cells based on network pharmacology and experimental verification.To search 127 drug targets through the TCMSP database and the Swiss Target Prediction database,then using the DisGeNET database to collect 287 disease targets.Constructed PPI network map by String online database.At the same time GO and KEGG enrichment analyses were carried out by using the DAVID database.Go enrichment analysis obtained 173 entries.The KEGG pathway screened the top 20 signaling pathways,including the HIF-1 pathway,VEGF pathway,PI3K-Akt pathway,and others.The molecular docking results showed that honokiol bound well to HIF-1α degrading enzymes PHDs,VHL.The CCK-8 method found that honokiol could effectively increase the survival rate of PC12 cells.Under normal conditions,HIF-1α,VEGF,PSD 95,and SYN 1 protein expression were elevated after honokiol administration(P<0.05,P<0.01).Under hypoxic conditions,HIF-1α and VEGF protein expression were significantly lower (P<0.05,P<0.01),and PSD 95 and SYN 1 protein expression were significantly higher after honokiol administration (P<0.01,P<0.001).In conclusion,honokiol has opposite regulatory effects on the HIF-1α-VEGF pathway,providing reliable theoretical and experimental support for the study of the anti-ischemia,antidepressant,and antitumor mechanisms of honokiol.

Key words: network pharmacology, honokiol, HIF-1α-VEGF pathway, regulation

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