Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RAR alpha-PPAR gamma-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice
文献类型：期刊论文
| 作者 | Zhao, Zhuohui2,3; Deng, Zhen-Tao1,2; Huang, Suling3 ; Ning, Mengmeng3; Feng, Ying3; Shen, Yu3; Zhao, Qin-Shi1,2; Leng, Ying2,3
|
| 刊名 | NUTRIENTS
 |
| 出版日期 | 2022-06-01 |
| 卷号 | 14期号:12页码:20 |
| 关键词 | Alisol B non-alcoholic steatohepatitis RAR alpha CD36 |
| DOI | 10.3390/nu14122411 |
| 通讯作者 | Zhao, Qin-Shi(qinshizhao@mail.kib.ac.cn) ; Leng, Ying(yleng@simm.ac.cn) |
| 英文摘要 | Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease worldwide, with no effective therapies available. Discovering lead compounds from herb medicine might be a valuable strategy for the treatment of NASH. Here, we discovered Alisol B, a natural compound isolated from Alisma orientalis (Sam.), that attenuated hepatic steatosis, inflammation, and fibrosis in high-fat diet plus carbon tetrachloride (DIO+CCl4)-induced and choline-deficient and amino acid-defined (CDA)-diet-induced NASH mice. RNA-seq showed Alisol B significantly suppressed CD36 expression and regulated retinol metabolism in NASH mice. In mouse primary hepatocytes, Alisol B decreased palmitate-induced lipid accumulation and lipotoxicity, which were dependent on CD36 suppression. Further study revealed that Alisol B enhanced the gene expression of RAR alpha with no direct RAR alpha agonistic activity. The upregulation of RAR alpha by Alisol B reduced HNF4 alpha and PPAR gamma expression and further decreased CD36 expression. This effect was fully abrogated after RAR alpha knockdown, suggesting Alisol B suppressed CD36 via regulating RAR alpha-HNF4 alpha-PPAR gamma cascade. Moreover, the hepatic gene expression of RAR alpha was obviously decreased in murine NASH models, whereas Alisol B significantly increased RAR alpha expression and decreased CD36 expression, along with the downregulation of HNF4 alpha and PPAR gamma. Therefore, this study showed the unrecognized therapeutic effects of Alisol B against NASH with a novel mechanism by regulating RAR alpha-PPAR gamma-CD36 cascade and highlighted Alisol B as a promising lead compound for the treatment of NASH. |
| WOS关键词 | FATTY LIVER ; HEPATIC STEATOSIS ; RECEPTOR ; ORIENTALE ; LIPOPROTEINS ; 23-ACETATE ; AGONIST ; CD36 |
| 资助项目 | State Key laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM2103ZZ-04] ; State Key Laboratory of Phytochemistry and Plant Resources in West China[P2022-KF06] |
| WOS研究方向 | Nutrition & Dietetics |
| 语种 | 英语 |
| WOS记录号 | WOS:000818185300001 |
| 出版者 | MDPI |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/301756]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhao, Qin-Shi; Leng, Ying |
| 作者单位 | 1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Zhuohui,Deng, Zhen-Tao,Huang, Suling,et al. Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RAR alpha-PPAR gamma-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice[J]. NUTRIENTS,2022,14(12):20. |
| APA | Zhao, Zhuohui.,Deng, Zhen-Tao.,Huang, Suling.,Ning, Mengmeng.,Feng, Ying.,...&Leng, Ying.(2022).Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RAR alpha-PPAR gamma-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice.NUTRIENTS,14(12),20. |
| MLA | Zhao, Zhuohui,et al."Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RAR alpha-PPAR gamma-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice".NUTRIENTS 14.12(2022):20. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。