PUBLICATION
Puerarin Induces Macrophage M2 Polarization to Exert Antinonalcoholic Steatohepatitis Pharmacological Activity via the Activation of Autophagy
- Authors
- Fang, X., Lan, X., Zhu, M., He, M., Sun, M., Cao, Y., Zhu, D., Guo, D., Luo, H.
- ID
- ZDB-PUB-240322-12
- Date
- 2024
- Source
- Journal of Agricultural and Food Chemistry 72(13): 7187-7202 (Journal)
- Registered Authors
- Keywords
- NASH, PAI-1, ULK1, autophagy, polarization, puerarin
- MeSH Terms
-
- Non-alcoholic Fatty Liver Disease*/drug therapy
- Non-alcoholic Fatty Liver Disease*/genetics
- Non-alcoholic Fatty Liver Disease*/metabolism
- Isoflavones*
- Animals
- Autophagy
- Plasminogen Activator Inhibitor 1
- Macrophage Activation
- Zebrafish
- Mice
- Macrophages
- Phosphatidylinositol 3-Kinases/metabolism
- PubMed
- 38515289 Full text @ J. Agric. Food Chem.
Citation
Fang, X., Lan, X., Zhu, M., He, M., Sun, M., Cao, Y., Zhu, D., Guo, D., Luo, H. (2024) Puerarin Induces Macrophage M2 Polarization to Exert Antinonalcoholic Steatohepatitis Pharmacological Activity via the Activation of Autophagy. Journal of Agricultural and Food Chemistry. 72(13):7187-7202.
Abstract
To determine the protective mechanism of puerarin against nonalcoholic steatohepatitis (NASH), the pharmacodynamic effects of puerarin on NASH were evaluated by using zebrafish, cells, and mice. Western blotting, flow cytometry, immunofluorescence, and qRT-PCR were used to detect the effects of puerarin on RAW264.7 autophagy and polarization. Key target interactions between autophagy and polarization were detected using immunoprecipitation. Puerarin regulated the M1/M2 ratio of RAW 264.7 cells induced by LPS + INF-γ. Transcriptomics revealed that PAI-1 is a key target of puerarin in regulating macrophage polarization. PAI-1 knockout reduced the number of M1-type macrophages and increased the number of M2-type macrophages. Puerarin regulated PAI-1 and was associated with macrophage autophagy. It increased p-ULK1 expression in macrophages and activated autophagic flux, reducing the level of PAI-1 expression. Stat3/Hif-1α and PI3K/AKT signaling pathways regulated the number of macrophage polarization phenotypes, reducing liver lipid droplet formation, alleviating liver structural abnormalities, decreasing the number of cytoplasmic vacuoles, and decreasing the area of blue collagen in NASH mice. Puerarin is a promising dietary component for NASH alleviation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping