Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells.
Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells.
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DOI：
10.3390/ijms222413354
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发表时间：
2021-12-12
影响因子：
5.6
通讯作者：
Itoh Y
中科院分区：
文献类型：
--
作者：
Kataoka S;Umemura A;Okuda K;Taketani H;Seko Y;Nishikawa T;Yamaguchi K;Moriguchi M;Kanbara Y;Arbiser JL;Shima T;Okanoue T;Itoh Y
慢性肝损伤可能导致肝纤维化，进而发展为肝硬化并最终导致肝衰竭。没有专门批准用于治疗肝纤维化的药物。天然产物和厚朴酚 (HNK) 是一种从广玉兰中提取的生物活性化合物，是治疗肝纤维化的潜在工具。尽管据报道 HNK 在大鼠纤维化模型中表现出抑制作用，但造成这种抑制的机制仍不清楚。在本研究中，我们在体内和体外评估了 HNK 对肝脏的抗纤维化作用。体内研究利用了小鼠肝纤维化模型，其中通过四氯化碳 (CCl4) 处理诱导纤维化。在体外研究中，用 HNK 处理 LX-2 人肝星状细胞 (HSC)，并分析纤维化标志物的表达、细胞活力、转化生长因子-β (TGF-β1)/SMAD 信号通路和自噬。 HNK 具有良好的耐受性，并在体内显着减弱 CCl4 诱导的肝纤维化。此外，HNK 通过下调 TGF-β1/SMAD 信号通路和自噬来减少 HSC 活化和胶原蛋白表达。这些结果表明，HNK 是通过抑制 HSC 中 TGF-β1/SMAD 信号传导和自噬来治疗肝纤维化的新的潜在候选药物。
Chronic liver injury may result in hepatic fibrosis, which can progress to cirrhosis and eventually liver failure. There are no drugs that are specifically approved for treating hepatic fibrosis. The natural product honokiol (HNK), a bioactive compound extracted from Magnolia grandiflora, represents a potential tool in the management of hepatic fibrosis. Though HNK has been reported to exhibit suppressive effects in a rat fibrosis model, the mechanisms accounting for this suppression remain unclear. In the present study, the anti-fibrotic effects of HNK on the liver were evaluated in vivo and in vitro. In vivo studies utilized a murine liver fibrosis model, in which fibrosis is induced by treatment with carbon tetrachloride (CCl4). For in vitro studies, LX-2 human hepatic stellate cells (HSCs) were treated with HNK, and expression of markers of fibrosis, cell viability, the transforming growth factor-β (TGF-β1)/SMAD signaling pathway, and autophagy were analyzed. HNK was well tolerated and significantly attenuated CCl4-induced liver fibrosis in vivo. Moreover, HNK decreased HSC activation and collagen expression by downregulating the TGF-β1/SMAD signaling pathway and autophagy. These results suggest that HNK is a new potential candidate for the treatment of hepatic fibrosis through suppressing both TGF-β1/SMAD signaling and autophagy in HSCs.
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DOI：
10.3390/v7092852
发表时间：
2015-09-10
期刊：
Viruses
影响因子：
--
作者：
Fang CY;Chen SJ;Wu HN;Ping YH;Lin CY;Shiuan D;Chen CL;Lee YR;Huang KJ
通讯作者：
Huang KJ
影响因子：
25.7
作者：
Asrani, Sumeet K.;Devarbhavi, Harshad;Kamath, Patrick S.
通讯作者：
Kamath, Patrick S.
影响因子：
6.7
作者：
Deng, Junfang;Qian, Yigang;Zheng, Shusen
通讯作者：
Zheng, Shusen
影响因子：
7.3
作者：
Chiang, Chih-Kang;Sheu, Meei-Ling;Liu, Shing-Hwa
通讯作者：
Liu, Shing-Hwa
影响因子：
3.8
作者：
Lin, Chien-Ju;Chen, Ta-Liang;Chen, Ruei-Ming
通讯作者：
Chen, Ruei-Ming