| Title | Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3/NF-kappa B pathway in mice |
| Authors | Wang, Qinyu Ou, Yangjie Hu, Guomin Wen, Cong Yue, Shanshan Chen, Cong Xu, Lu Xie, Jiawei Dai, Hui Xiao, Han Zhang, Youyi Qi, Rong |
| Affiliation | Peking Univ, Inst Cardiovasc Sci, Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China Peking Univ, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing, Peoples R China Peking Univ, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing, Peoples R China Peking Univ, Dept Cardiol, Hosp 3, Beijing, Peoples R China Peking Univ, Inst Vasc Med, Hosp 3, Beijing, Peoples R China Peking Univ, NHC Key Lab Cardiovasc Mol Biol & Regulatory Pept, Hosp 3, Beijing, Peoples R China Peking Univ, Beijing Key Lab Cardiovasc Receptors Res, Hosp 3, Beijing, Peoples R China Shihezi Univ, Sch Basic Med Sci, Shihezi, Peoples R China Peking Univ, Sch Basic Med Sci, Dept Immunol, Hlth Sci Ctr, Beijing, Peoples R China |
| Keywords | NF-KAPPA-B NLRP3 INFLAMMASOME ATHEROSCLEROSIS PATHOGENESIS PROGRESSION ACTIVATION MECHANISMS FIBROSIS STRESS GUIDE |
| Issue Date | Apr-2020 |
| Publisher | BRITISH JOURNAL OF PHARMACOLOGY |
| Abstract | Background and Purpose Naringenin, a flavonoid compound with strong anti-inflammatory activity, attenuated non-alcoholic fatty liver disease (NAFLD) induced by a methionine-choline deficient (MCD) diet in mice. However, the mechanisms underlying this suppression of inflammation and NAFLD remain unknown. Experimental Approach WT and NLRP3(-/-) mice were fed with MCD diet for 7 days to induce NAFLD and were given naringenin by gavage at the same time. in vitro experiments used HepG2 cells, primary hepatocytes, and Kupffer cells (KCs) stimulated by LPS or LPS plus oleic acid (OA). Key Results Treating WT mice with naringenin (100 mg center dot kg(-1)center dot day(-1)) attenuated hepatic lipid accumulation and inflammation in the livers of mice given the MCD diet. NLRP3(-/-) mice showed less hepatic lipid accumulation than WT mice, but naringenin did not ameliorate hepatic lipid accumulation further in NLRP3(-/-) mice. Treating the HepG2 cells with naringenin or NLRP3 inhibitor MCC950 reduced lipid accumulation. Naringenin inhibited activation of the NLRP3/NF-kappa B pathway stimulated by OA together with LPS. In KCs isolated from WT mice, naringenin inhibited NLRP3 expression. Naringenin also inhibited lipid deposition, NLRP3 and IL-1 beta expression in WT hepatocytes but was not effective in NLRP3(-/-) hepatocytes. After re-expressing NLRP3 in NLRP3(-/-) hepatocytes by adenovirus, the anti-lipid deposition effect of naringenin was restored. Conclusion and Implications Naringenin prevented NAFLD via down-regulating the NLRP3/NF-kappa B signalling pathway both in KCs and in hepatocytes, thus attenuating inflammation in the mice livers. |
| URI | http://hdl.handle.net/20.500.11897/585681 |
| ISSN | 0007-1188 |
| DOI | 10.1111/bph.14938 |
| Indexed | SCI(E) Scopus |
| Appears in Collections: | 基础医学院 分子心血管学教育部重点实验室 第三医院 |
