Schizandrin C regulates lipid metabolism and inflammation in liver fibrosis by NF-κB and p38/ERK MAPK signaling pathways.
Schizandrin C regulates lipid metabolism and inflammation in liver fibrosis by NF-κB and p38/ERK MAPK signaling pathways.
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DOI：
10.3389/fphar.2023.1092151
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
肝纤维化被认为是一种持续的创面愈合反应和代谢综合征，其治疗对慢性肝病具有重要意义。五味子乙素C是五味子中的一种木脂素，具有抗氧化作用和抗脂质过氧化作用，具有抗肝损伤的作用。本研究采用C57BL/6J小鼠建立CCl4肝纤维化模型，五味子甲素C具有抗肝纤维化作用，表现为血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和总胆红素活性降低，羟脯氨酸含量降低，肝组织结构恢复，胶原沉积减少。此外，五味子甲素C还可降低肝脏中α-平滑肌肌动蛋白和Ι型胶原的表达。体外实验还显示，五味子甲素C可抑制LX-2和HSC-T6细胞中肝星状细胞的激活。此外，脂类组学和实时定量聚合酶链式反应分析表明，五味子乙素C调节肝脏中的脂类和相关代谢酶。此外，五味子甲素C可下调炎症因子的表达水平，同时降低IκB-Kinase-β、核因子kappaB p65和磷酸化核因子kappaBp65的蛋白水平。最后，五味子甲素C抑制了在CCl4肝纤维化中激活的p38MAP和细胞外信号调节蛋白激酶的磷酸化。综上所述，五味子甲素可通过核因子kappa-B和p38/ERK MAPK信号通路调节脂质代谢和炎症反应，从而减轻肝纤维化。这些发现支持五味子甲素作为治疗肝纤维化的潜在药物。
Liver fibrosis is considered a sustained wound healing response and metabolic syndrome, and its therapy is of great significance for chronic liver disease. Schizandrin C, as one lignan from hepatic protectant Schisandra chinensis, can depress the oxidative effect and lipid peroxidation, and protect against liver injury. In this study, C57BL/6J mice were used to estimate a liver fibrosis model by CCl4, and Schizandrin C exerted an anti-hepatic fibrosis effect, as evidenced by decreased alanine aminotransferase, aspartate aminotransferase and total bilirubin activities in serum, lower hydroxyproline content, recuperative structure and less collagen accumulation in the liver. In addition, Schizandrin C reduced the expressions of alpha-smooth muscle actin and type Ι collagen in the liver. In vitro experiments also revealed that Schizandrin C attenuated hepatic stellate cell activation in both LX-2 and HSC-T6 cells. Furthermore, lipidomics and quantitative real-time PCR analysis revealed that Schizandrin C regulated the lipid profile and related metabolic enzymes in the liver. In addition, the mRNA levels of inflammation factors were downregulated by Schizandrin C treatment, accompanied by lower protein levels of IκB-Kinase-β, nuclear factor kappa-B p65, and phospho-nuclear factor kappa-B p65. Finally, Schizandrin C inhibited the phosphorylation of p38 MAP kinase and extracellular signal-regulated protein kinase, which were activated in the CCl4 fibrotic liver. Taken together, Schizandrin C can regulate lipid metabolism and inflammation to ameliorate liver fibrosis by nuclear factor kappa-B and p38/ERK MAPK signaling pathways. These findings supported Schizandrin C as a potential drug for liver fibrosis.
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影响因子：
81.5
作者：
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通讯作者：
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