Hyperoside attenuates non-alcoholic fatty liver disease through targeting Nr4A1 in macrophages

•Hyperoside attenuates HFD-induced hepatic steatosis, fibrosis and systemic IR.•Hyperoside inhibits the HFD-induced inflammatory response and regulates macrophage polarization.•Hyperoside attenuates NAFLD through the upregulation of Nr4A1 expression in macrophages. Non-alcoholic fatty liver disease...

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Bibliographic Details
Published in:International immunopharmacology 2021-05, Vol.94, p.107438-107438, Article 107438
Main Authors: Sun, Bing, Zhang, Ranteng, Liang, Zicong, Fan, Aoqiang, Kang, Dongmei
Format: Article
Language:English
Subjects:
Animals
Biological effects
Diet, High-Fat
Fatty liver
Flavonoids
Herbal medicine
High fat diet
Hyperoside
Inflammation
Inflammatory response
Insulin
Insulin resistance
Liver
Liver - drug effects
Liver - metabolism
Liver - pathology
Liver Cirrhosis - drug therapy
Liver Cirrhosis - metabolism
Liver diseases
Macrophages
Macrophages - drug effects
Male
Medicinal plants
Mice
Mice, Inbred C57BL
Mice, Knockout
NAFLD
NASH
Non-alcoholic Fatty Liver Disease - drug therapy
Non-alcoholic Fatty Liver Disease - metabolism
Nr4A1
Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics
Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism
Physiological effects
Polarization
Quercetin - analogs & derivatives
Quercetin - pharmacology
Quercetin - therapeutic use
Steatosis
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Summary:•Hyperoside attenuates HFD-induced hepatic steatosis, fibrosis and systemic IR.•Hyperoside inhibits the HFD-induced inflammatory response and regulates macrophage polarization.•Hyperoside attenuates NAFLD through the upregulation of Nr4A1 expression in macrophages. Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and a systemic pro-inflammatory response. To date, no medications for NAFLD have been approved by relevant governmental agencies. Emerging evidence indicates that innate immune mechanisms are pivotal drivers of inflammation and other pathological manifestations observed in NAFLD. Hyperoside, a flavonoid compound mainly found in medicinal plants, has many biological effects, but the role of hyperoside in the physiological process of NAFLD is poorly defined. This study demonstrated that hyperoside exerts protective effects against high-fat diet (HFD)-induced NAFLD and regulates macrophage polarization in an Nr4A1-dependent manner. After 16 weeks on a HFD, hepatic steatosis, insulin resistance, and inflammatory responses were significantly ameliorated in hyperoside-treated HFD-fed wild-type mice, and hyperoside facilitated the polarization of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 subtype. Nr4A1 was found to be upregulated in hyperoside-treated HFD-fed mice, and hyperoside did not improve HFD-induced NAFLD or regulate macrophage polarization in Nr4A1-deficient mice. In conclusion, hyperoside may have therapeutic potential in preventing the pathological progression of NAFLD.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2021.107438