Chrysophanol-8-O-glucoside protects mice against acute liver injury by inhibiting autophagy in hepatic stellate cells and inflammatory response in liver-resident macrophages.
Chrysophanol-8-O-glucoside protects mice against acute liver injury by inhibiting autophagy in hepatic stellate cells and inflammatory response in liver-resident macrophages.
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菊醇-8-O-葡萄糖苷通过抑制肝星状细胞的自噬和肝居住巨噬细胞的炎症反应来保护小鼠免受急性肝损伤。
DOI：
10.3389/fphar.2022.951521
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发表时间：
2022
影响因子：
5.6
通讯作者：
Xie, Cai-Feng
中科院分区：
文献类型：
--
作者：
Wang, Tao;Lu, Zhuo;Qu, Xin-Hui;Xiong, Zi-Ying;Wu, Ya-Ting;Luo, Yong;Zhang, Zi-Yu;Han, Xiao-Jian;Xie, Cai-Feng
急性肝衰竭（ALF）是一种不利的疾病，其特征是肝功能迅速丧失和高死亡率。 Chrysophanol-8-O-glucoside (CPOG) 是从大黄中分离出来的蒽醌衍生物。本研究旨在评估CPOG对脂多糖（LPS）/D-GalN诱导的ALF的保护作用及其潜在机制。建立LPS/D-GalN诱导的小鼠ALF模型以及RAW 264.7和LX2细胞的LPS治疗模型。苏木精-伊红 (H&E) 染色表明，CPOG 可改善 LPS/D-GalN 诱导的肝损伤并提高死亡率。分子、qPCR 和 ELISA 结果表明，CPOG 减轻了 LPS/D-GalN 诱导的体内丙氨酸转氨酶和天冬氨酸转氨酶的释放以及 TNF-α 和 IL-1β 的分泌。 LPS/D-GalN 诱导的细胞内 ROS 产生也被肝组织中的 CPOG 减弱。此外，CPOG 减弱 RAW 264.7 细胞中 ROS 的产生并抑制 p-IκB 和 p-p65 的表达以及 LPS 刺激的 TNF-α 和 IL-1β 的表达。此外，CPOG 通过减弱 LX2 细胞中 ROS 的产生和抑制 MAPK 信号传导，减轻 LPS 诱导的 LC3B、p62、ATG5 和 Beclin1 的上调。综上所述，我们的数据表明 CPOG 通过抑制氧化应激、炎症反应和自噬来防止 LPS/D-GalN 诱导的 ALF。这些结果表明CPOG可能成为临床治疗ALF的潜在药物。
Acute liver failure (ALF) is an unfavorable condition characterized by the rapid loss of liver function and high mortality. Chrysophanol-8-O-glucoside (CPOG) is an anthraquinone derivative isolated from rhubarb. This study aims to evaluate the protective effect of CPOG on lipopolysaccharide (LPS)/D-GalN-induced ALF and its underlying mechanisms. LPS/D-GalN-induced mice ALF model and LPS treatment model in RAW 264.7 and LX2 cells were established. It was found that CPOG ameliorated LPS/D-GalN-induced liver injury and improved mortality as indicated by Hematoxylin-eosin (H&E) staining. Molecularly, qPCR and ELISA results showed that CPOG alleviated LPS/D-GalN-induced release of alanine aminotransferase and aspartate transaminase and the secretion of TNF-α and IL-1β in vivo. LPS/D-GalN-induced intracellular ROS production was also attenuated by CPOG in liver tissue. Further, CPOG attenuated ROS generation and inhibited the expression of p-IκB and p-p65 as well as the expression of TNF-α and IL-1β stimulated by LPS in RAW 264.7 cells. In addition, CPOG alleviated LPS-induced up-regulation of LC3B, p62, ATG5 and Beclin1 by attenuating ROS production and inhibiting MAPK signaling in LX2 cells. Taken together, our data indicated that the CPOG protected against LPS/D-GalN-induced ALF by inhibiting oxidative stress, inflammation response and autophagy. These findings suggest that CPOG could be potential drug for the treatment of ALF in clinic.
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影响因子：
4.1
作者：
Muniandy K;Gothai S;Badran KMH;Suresh Kumar S;Esa NM;Arulselvan P
通讯作者：
Arulselvan P
影响因子：
3.8
作者：
Heijnen, BHM;Straatsburg, IH;van Gulik, TM
通讯作者：
van Gulik, TM
槐果碱通过抑制氧化应激、炎症和细胞凋亡来减轻 LPS 引起的肝损伤并提高小鼠的存活率
影响因子：
4.6
作者：
Jiang Z;Meng Y;Bo L;Wang C;Bian J;Deng X
通讯作者：
Deng X
影响因子：
7.2
作者：
Oeckinghaus, Andrea;Ghosh, Sankar
通讯作者：
Ghosh, Sankar
影响因子：
2.7
作者：
Mondal P;Roy S;Loganathan G;Mandal B;Dharumadurai D;Akbarsha MA;Sengupta PS;Chattopadhyay S;Guin PS
通讯作者：
Guin PS