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竹节参苷 I 通过激活 eNOS-VEGF 信号通路促进血管生成。

Tubeimoside I promotes angiogenesis via activation of eNOS-VEGF signaling pathway.

机构信息

Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Institute of Life Sciences, Chongqing Medical University, Chongqing, 400010, China.

Institute of Life Sciences, Chongqing Medical University, Chongqing, 400010, China.

出版信息

J Ethnopharmacol. 2021 Mar 1;267:113642. doi: 10.1016/j.jep.2020.113642. Epub 2020 Nov 29.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Tubeimoside I (TBM) is a triterpenoid saponin purified from tubeimu (tuber of Bolbostemma paniculatum (Maxim.) Franquet). In traditional Chinese medicine, tubeimu had been used to treat acute mastitis, snake bites, detoxication, inflammatory diseases, and tumors for over 1000 years.

AIM OF THE STUDY

This study aimed to investigate whether TBM could promote angiogenesis and how to promote angiogenesis.

MATERIALS AND METHODS

In vivo, the pro-angiogenic effects of TBM were examined using the hindlimb ischemia model. After the ischemia operation, 1 mg/kg/day TBM was given via intraperitoneal injection for 28 days and the recovery of blood flow was monitored by Doppler scanner every 7 days. The capillary density in gastrocnemius muscle was detected by immunofluorescence. Expression of related proteins were determined by western blotting. In vitro, the pro-angiogenic effects of TBM on HUVECs were examined by Cell Counting Kit-8, scratch assay, endothelial cell tube formation assay and western blotting.

RESULTS

TBM improved recovery from hindlimb ischemia in C57BL/6 mice. TBM promoted endothelial cell viability, migration and tube formation in HUVECs. TBM could activate eNOS-VEGF signaling pathway by enhancing expression of eNOS. And TBM's pro-angiogenesis effects could be abolished by L-NAME (an inhibitor of eNOS).

CONCLUSIONS

TBM promoted angiogenesis via the activation of eNOS-VEGF signaling pathway and TBM could be a novel agent for therapeutic angiogenesis in ischemic diseases.

摘要

民族药理学相关性

通关藤苷 I(TBM)是从通关藤(管花马兜铃的根茎)中分离得到的一种三萜皂苷。在中国传统医学中,通关藤已被用于治疗急性乳腺炎、蛇咬伤、解毒、炎症性疾病和肿瘤超过 1000 年。

研究目的

本研究旨在探讨 TBM 是否具有促进血管生成的作用以及如何促进血管生成。

材料与方法

在体内,通过后肢缺血模型研究 TBM 的促血管生成作用。在缺血手术后,通过腹腔注射给予 1mg/kg/天 TBM,共 28 天,并每隔 7 天通过多普勒扫描仪监测血流恢复情况。通过免疫荧光检测腓肠肌中的毛细血管密度。通过 Western blot 检测相关蛋白的表达。在体外,通过细胞计数试剂盒-8 检测、划痕实验、内皮细胞管形成实验和 Western blot 检测 TBM 对 HUVECs 的促血管生成作用。

结果

TBM 改善了 C57BL/6 小鼠后肢缺血的恢复情况。TBM 促进了 HUVECs 中内皮细胞的活力、迁移和管形成。TBM 通过增强 eNOS 的表达激活了 eNOS-VEGF 信号通路。并且 TBM 的促血管生成作用可以被 L-NAME(eNOS 抑制剂)所阻断。

结论

TBM 通过激活 eNOS-VEGF 信号通路促进血管生成,TBM 可能是缺血性疾病治疗性血管生成的一种新型药物。

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