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DT-13在体内和体外均可改善肿瘤坏死因子-α诱导的内皮细胞一氧化氮生成。

DT-13 ameliorates TNF-α-induced nitric oxide production in the endothelium in vivo and in vitro.

作者信息

Fan Ruiping, Han Yuwei, Han Han, Chen Zhengdong, Yu Boyang, Kou Junping, Zhang Yuanyuan

机构信息

Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China.

Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China; Institute of Neurology, General Hospital of Shenyang Military Command, Shenyang, Liaoning, 110016, China.

出版信息

Biochem Biophys Res Commun. 2018 Jan 1;495(1):1175-1181. doi: 10.1016/j.bbrc.2017.11.009. Epub 2017 Nov 21.

Abstract

The steroidal saponin DT-13 (25(R,S)-ruscogenin-1-O-[β-d-glucopyranosyl-(1 → 2)][β-d-xylopyranosyl-(1 → 3)]-β-d-fucopyranoside), one of the major active compounds of the herb Liriope muscari (Decne.), exhibits significant anti-inflammatory, anti-tumor and cardioprotective effects. This study aimed to explore the protective effect of DT-13 on endothelium through regulating of nitric oxide production induced by Tumor necrosis factor-α (TNF-α). The results demonstrated that DT-13 inhibited inflammatory cell infiltration and thus played a protective effect on endothelial cells in vivo, as shown by hematoxylin-eosin (H&E) staining and immunohistochemical staining. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that DT-13 could suppress the TNF-α-induced upregulation of reactive oxygen species (ROS), tumor necrosis factor receptor (TNFR), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and nitric oxide in vivo dose-dependently and suppressed production of nitric oxide in vitro as shown by DAF-FMDA. Western blotting results indicated that DT-13 could down-regulate phosphorylation of endothelial nitric oxide synthase (eNOS) significantly in TNF-α-induced human umbilical vein endothelial cells (HUVECs). Taken together, we speculate that DT-13 inhibits endothelium vascular inflammation through regulating nitric oxide production and the expression of ROS, TNFR, IL-8, MCP-1, which are associated with inflammation.

摘要

甾体皂苷DT-13(25(R,S)-鲁斯可皂苷元-1-O-[β-D-吡喃葡萄糖基-(1→2)][β-D-吡喃木糖基-(1→3)]-β-D-岩藻糖吡喃糖苷)是麦冬(Decne.)的主要活性成分之一,具有显著的抗炎、抗肿瘤和心脏保护作用。本研究旨在通过调节肿瘤坏死因子-α(TNF-α)诱导的一氧化氮生成来探讨DT-13对内皮细胞的保护作用。结果表明,苏木精-伊红(H&E)染色和免疫组化染色显示,DT-13抑制炎症细胞浸润,从而在体内对内皮细胞发挥保护作用。酶联免疫吸附测定(ELISA)结果表明,DT-13能在体内剂量依赖性地抑制TNF-α诱导的活性氧(ROS)、肿瘤坏死因子受体(TNFR)、白细胞介素-8(IL-8)、单核细胞趋化蛋白-1(MCP-1)和一氧化氮上调,并如DAF-FMDA所示在体外抑制一氧化氮的生成。蛋白质印迹结果表明,DT-13能显著下调TNF-α诱导的人脐静脉内皮细胞(HUVECs)中内皮型一氧化氮合酶(eNOS)的磷酸化。综上所述,我们推测DT-13通过调节一氧化氮生成以及与炎症相关的ROS、TNFR、IL-8、MCP-1的表达来抑制内皮血管炎症。

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