期刊
JOURNAL OF NATURAL MEDICINES
卷 75, 期 3, 页码 540-552出版社
SPRINGER JAPAN KK
DOI: 10.1007/s11418-021-01491-4
关键词
Dehydroabietic acid; Nonalcoholic fatty liver disease; Ferroptosis; ROS; Nrf2-ARE
资金
- Postdoctoral Foundation of China [2018M642761]
- Special Research Project of Henan Province on Traditional Chinese Medicine [2018ZYD12]
- Key Scientific Research Project Plan of Henan Higher Education Institutions [19A360021]
- Program for Innovative Research Team (in Science and Technology) in University of Henan Province [21IRTSTHN026]
- Leading Talents Program of Zhongyuan Science and Technology Innovation [204200510022]
The study found that dehydroabietic acid (DA) can improve nonalcoholic fatty liver disease (NAFLD), reduce the accumulation of lipid peroxides, inhibit hepatic ferroptosis, and reduce the accumulation of reactive oxygen species by activating the Nrf2 antioxidant response pathway.
The accumulation of iron-dependent lipid peroxides is one of the important causes of NAFLD. The purpose of this study is to explore the effect of dehydroabietic acid (DA) on ferroptosis in nonalcoholic fatty liver disease (NAFLD) mice and its possible mechanisms. DA improved NAFLD and reduced triglycerides (TG), total cholesterol (TC), and lipid peroxidation level and inhibited ferroptosis in the liver of HFD-induced mice. DA binds with Keap1 to form 3 stable hydrogen bonds at VAL512 and LEU557 and increased nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elemen (ARE) luciferase activity. DA promoted the expression downstream of Nrf2 such as heme oxygenase-1 (HO-1), glutathione (GSH) and its peroxidase 4 (GPX4), so as to eliminate the accumulation of reactive oxygen species (ROS) and reduce lipid peroxides malondialdehyde (MDA) in the liver. DA inhibited ferroptosis and increased the expression of key genes such as ferroptosis suppressor protein 1 (FSP1) in vitro and vivo. In all, DA may bind with Keap1, activate Nrf2-ARE, induce its target gene expression, inhibit ROS accumulation and lipid peroxidation, and reduce HFD-induced NAFLD. [GRAPHICS] .
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