课题基金基金详情
藏药独一味环烯醚萜苷 “干黄水”功效促血管生成药效物质基础及分子机制研究
结题报告
批准号:
81973567
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
潘正
依托单位:
学科分类:
民族药学
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
潘正
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中文摘要
藏药独一味创伤修复疗效确切,但物质基础和作用机制不明确,我们研究证实独一味总环烯醚萜苷(IGLR)的体外抗炎和体内促血管生成活性;鉴于独一味“干黄水”(抗炎)治疗黄水病皮肤溃疡,与糖尿病伤口溃疡的共性特征,结合前期实验结果,提出“IGLR激活p38/MK2通路-干黄水-抗炎-促血管生成”的科学假说。为阐明IGLR具体的药效物质和分子机制,拟通过UPLC-QTOF/MS代谢组学和Capto DEAE生物纯化技术,识别、制备独一味抗炎促血管生成活性物质;通过transwell和主动脉环等实验技术,揭示活性物质通过巨噬细胞与内皮细胞的胞间信号通信,动态加速三维血管新生的机制;论证药效物质在创伤修复过程中对炎症反应、胶原沉着和血管生成的整体调控优势;采用siRNA干扰技术和化学阻断剂,正反论证药效物质激活p38/MK2信号通路抗炎促血管生成的分子机制。为临床开发治疗难愈性创伤的藏药新药提供新思路。
英文摘要
Lamiophlomis rotata (L.rotata) is a Tibetan medicinal herb used for the treatment of knife and gun acute wounds for many centuries. the “huang water disease “ are similar with non-healing nature of diabetic foot ulcers and other chronic wounds, although our previous studies showed that total iridoid glycosides of L. rotata (IGLR) are the major active components of wound healing effects, in vivo results demonstrated a significant reduction of angiogenesis, and in vitro results demonstrated IGLR with anti-inflammation active, and a combination of pathway analysis and other systems biology tools confirmed the p38/MK2 signaling pathway played a central role in tissue regeneration, angiogenesis and anti-inflammation. However, it is uncertain which of iridoid glycosides have the anti-inflammation and angiogenesis effects in wound healing, and the molecular mechanisms underlying the effects of IGLR still remains poorly understood. The aim of the present study was to investigate the anti-inflammation and angiogenesis effects of IGLR in vitro and in vivo mechanistic. With pharmacokinetics screening for multi-components absorbed in the rat plasma after oral administration, target compounds which are absorbed in blood would be screening as biomarker. A comprehensive strategy that included chemoinformatics, bioinformatics and network biology methods wound be employed to unravel novel insights into the active compounds of L.rotata oral liquid and to identify the common therapeutic targets and processes for wound healing treatment. In order to ravel which iridoid glycosides activated Mφ macrophages alternatively M2 phenotypes, FITC-conjugated anti-goat antibody, F4/80-positive TNF-α-positive cells will define as an M1 phenotype and F4/80-positive IL-13–positive cells as an M2 phenotype. The active of iridoid glycosides promoting angiogenesis will conduct with aortic ring cultures, and the migration of endothelial cells by IGLR inducing M2 phenotypes will conduct by tranwell; A full-thickness skin wound was generated on the back of the diabetic mice and treated with iridoid glycosides or vehicle topically. Furthermore, iridoid glycosides promoted infiltration of macrophages, which produced vascular endothelial growth factor in granulation tissues. In vitro, which IGLR promoted capillary morphogenesis on endothelial cells. A simple strategy of topically applied iridoid glycosides may have significant therapeutic potential for enhanced wound healing in patients with impaired microcirculation such as that in diabetes.
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DOI:10.1016/j.jep.2023.116193
发表时间:2023-02
期刊:Journal of ethnopharmacology
影响因子:5.4
作者:Lei Lei-Lei;Guoguo Wan;Xiaoyu Geng;Jianguo Sun;Y. Zhang;Jianwei Wang;Congwen Yang;Zheng Pan
通讯作者:Lei Lei-Lei;Guoguo Wan;Xiaoyu Geng;Jianguo Sun;Y. Zhang;Jianwei Wang;Congwen Yang;Zheng Pan
DOI:10.1186/s13020-023-00723-x
发表时间:2023-02-24
期刊:CHINESE MEDICINE
影响因子:4.9
作者:Wan, Guoguo;Chen, Zhiwei;Lei, Lei;Geng, Xiaoyu;Zhang, Yi;Yang, Congwen;Cao, Wenfu;Pan, Zheng
通讯作者:Pan, Zheng
DOI:10.3390/ijms24065933
发表时间:2023-03-21
期刊:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
影响因子:5.6
作者:Hu, Jinyuan;Liu, Yuanyuan;Pan, Zheng;Huang, Xuekuan;Wang, Jianwei;Cao, Wenfu;Chen, Zhiwei
通讯作者:Chen, Zhiwei
DOI:10.1016/j.jep2024.117720
发表时间:2024
期刊:Journal of Ethnopharmacology
影响因子:--
作者:Congwen Yang;Xiaoyu Geng;Guoguo Wan;Liang Song;Ying Wang;Guoying Zhou;Jianwei Wang;Zheng Pan
通讯作者:Zheng Pan
基于质谱成像技术的复方枣仁胶囊药效物质药代动力学及镇静催眠作用机制研究
  • 批准号:
    --
  • 项目类别:
    省市级项目
  • 资助金额:
    0.0万元
  • 批准年份:
    2025
  • 负责人:
    潘正
  • 依托单位:
国内基金
海外基金