Hesperetin derivative-14 alleviates inflammation by activating PPAR-γ in mice with CCl4-induced acute liver injury and LPS-treated RAW264.7 cells
Hesperetin derivative-14 alleviates inflammation by activating PPAR-γ in mice with CCl4-induced acute liver injury and LPS-treated RAW264.7 cells
复制标题
橙皮素衍生物 14 通过激活 CCl4 诱导的急性肝损伤小鼠和 LPS 处理的 RAW264.7 细胞中的 PPAR-γ 减轻炎症
DOI：
10.1016/j.toxlet.2017.04.008
复制
发表时间：
2017-05-15
影响因子：
3.5
通讯作者：
Li, Jun
中科院分区：
文献类型：
--
作者：
Chen, Xin;Ding, Hai-Wen;Li, Jun
橙皮素是一种天然存在于柑桔果皮中的黄酮苷类化合物。（芸香科）。研究表明橙皮素具有抗炎、抗肿瘤、抗氧化和神经保护等多种药理作用。橙皮素衍生物-14（HD-14）是橙皮素的衍生物，其水溶性和生物利用度得到改善。在这项研究中，我们表明，HD-14（2 μ M）显着减轻炎症的LPS处理的RAW 264.7细胞，此外，HD-14（100 mg/kg）表现出保肝作用和抗炎作用的C57 BL/6 J小鼠与四氯化碳诱导的急性肝损伤。此外，证明HD-14在体内和体外显著上调PPAR-gamma的表达。有趣的是，PPAR-gamma的过表达对TNF-α、IL-6和IL-1 β的表达具有抗炎作用，而用小干扰RNA敲低PPAR-gamma在LPS处理的RAW 264.7细胞中具有促炎作用。因此，我们的研究结果表明，HD-14至少部分通过激活PPAR-gamma表达来减轻炎症。进一步的研究发现HD-14通过上调PPAR-gamma显著抑制p-JAK 1和p-STAT 1的表达。总之，这些结果表明，HD-14作为PPAR-gamma的激活剂，JAK 1/STAT 1信号通路可能参与炎症的进展。总的来说，HD-14可用作治疗急性肝损伤的潜在抗炎单体化合物。
Hesperetin is a flavanone glycoside compound naturally occurring in the fruit peel of Citrusaurantium L. (Rutaceae). Previous studies revealed that hesperetin possesses various pharmacological effects, including anti-inflammation, anti-tumor, anti-oxidant and neuroprotective properties. Hesperetin derivative-14 (HD-14) is a derivative of hesperetin improved in water solubility and bioavailability. In this study, we indicated that HD-14 (2 mu M) significantly attenuated inflammation in LPS-treated RAW264.7 cells, besides, HD-14 (100 mg/kg) exhibited hepato-protective effects and anti-inflammatory effects on C57BL/6J mice with CCl4-induced acute liver injury. In addition, it was demonstrated that HD-14 dramatically up-regulated the expression of PPAR-gamma in vivo and in vitro. Interestingly, over-expression of PPAR-gamma had anti-inflammatory effects on the expressions of TNF-alpha, IL-6, and IL-1 beta, whereas, knockdown of PPAR-gamma with small interfering RNA had pro-inflammatory effects in LPS-treated RAW264.7 cells. Thus, our findings demonstrated that HD-14 alleviated inflammation by activating PPAR-gamma expression at least in part. Further studies founded that HD-14 remarkably inhibited the expression of p-JAK1 and p-STAT1 through up-regulating PPAR-gamma. Together, these results suggested that HD-14 served as an activator of PPAR-gamma and the JAK1/STAT1 signaling pathway may be involved in the progress of inflammation. Collectively, HD-14 may be utilized as a potential anti-inflammation monomeric compound in the treatment of acute liver injury.