Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis.
Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis.
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芍药苷通过上调 SOCS3 抑制 ASK1-TF 轴以减轻放射性肠炎。
DOI：
10.3389/fphar.2022.743708
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发表时间：
2022
影响因子：
5.6
通讯作者：
Yang M
中科院分区：
文献类型：
--
作者：
Sheng L;Hu F;Yu H;Tao X;Jia R;Gu Y;Chen L;Kong H;Miao C;Fei W;Yang Y;Jia J;Zhu X;He X;Hu L;Ma J;Liu WT;Yang M
放射性肠炎是放射治疗的主要不良反应之一，目前对其病因知之甚少，治疗选择有限。肠道炎症和缺血是放射性肠炎的核心机制。细胞因子信号转导抑制因子3(SOCS3)是一种内源性“炎症刹车”。我们推测，芍药苷，一种蒎烷类单萜苦苷，可以增加SOCS3的表达，以减少炎症和缺血，并改善小鼠的肠炎。用激光多普勒血流仪检测肠血流的变化。以RAW264.7和人脐静脉内皮细胞为实验材料，研究了芍药苷的作用机制。据观察，辐射导致小鼠高死亡率、肠道炎症反应和低血流量。在接受放射治疗的小鼠中，芍药苷能有效缓解肠道萎缩，预防血栓形成，改善放射性肠炎，降低死亡率。此外，在体内外实验中，芍药苷可促进生长停滞特异基因6(Gas6)的释放和Ax1受体的磷酸化，从而诱导SOCS3的表达，抑制p-凋亡信号调节蛋白1和组织因子的表达。基于我们的发现，我们认为芍药苷可能通过激活Gas6/Ax1/SOCS3轴，从而减少肠道炎症和缺血，从而有效地减轻放射性肠炎。
Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous “inflammation brake.” We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Laser Doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor in vivo and in vitro. Based on our findings, we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis via the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia.
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