课题基金基金详情
柴胡和白芍醋炙配伍调控IDO1/GCN2信号通路重构免疫微环境增强抗肝纤维化的物质基础及分子机制研究
结题报告
批准号:
81973481
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
曹岗
依托单位:
学科分类:
中药炮制
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
曹岗
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中文摘要
醋炙入肝是中药炮制经典理论之一,但目前常以单味药研究为主,鲜有将其配伍组方开展研究,导致中药炮制归经研究与中医临床用药相脱节,不能全面揭示炮制归经的科学内涵。“柴胡–白芍”是中医临床疏肝理脾常用药对,其肝保护疗效确切。我们前期研究发现柴胡和白芍醋炙后化学物质发生了量变和质变,疏肝理脾作用增强,但柴胡和白芍醋炙配伍增效的物质基础和机制尚未明确。本项目以“柴胡–白芍”药对为代表,采用“靶向垂钓活性成分/代谢产物-HSCCC×HPLC高效分离制备”模式,通过基因重组、细胞免疫生物学和药物代谢等手段探讨柴胡和白芍醋炙配伍增强调控IDO1/GCN2通路干预肝纤维化免疫微环境机制,并利用肝脏细胞靶向垂钓其增效活性组分,明确柴胡和白芍醋炙配伍抗肝纤维化增效的物质基础。本研究可为中药炮制归经配伍理论及抗肝纤维化药物设计提供新思路并推动中医药创新理论的发展。
英文摘要
Stir baking with vinegar as liver medication is a classic theory of Chinese medicine. However,most studies have focused on single-substance drugs and few have focused on combination formulas. Thus, research on the meridian-tropism theory of traditional Chinese medicine is separated from the clinical applications of traditional Chinese medicine, and the results cannot reveal the entire scientific connotation of the meridian tropism of processed Chinese medicine. Radix bupleuri–Radix paeoniae alba is a common drug pair for soothing the liver and regulating the spleen with known hepatoprotective effects. Our previous studies have shown that the chemical substances in Radix bupleuri and Radix paeoniae alba quantitatively and qualitatively change after stir baking with vinegar. With the enhanced effect of soothing the liver and regulating the spleen, this formula intervenes with tryptophan metabolism in the microenvironment and controls the Kupffer cells (KCs) regulation effect by downregulating IDO1 and upregulating GCN2, thereby exerting an antihepatic-fibrosis effect. However, the material basis and mechanism of stir baking with vinegar for improved activity have not yet been clarified. In this study, using Radix bupleuri–Radix paeoniae alba as a representative, a target-fishing active ingredient/metabolite-HSCCC×HPLC separation and preparation mode. Stir baking with vinegar as liver medication is a classic theory of Chinese medicine. However, most studies have focused on single-substance drugs and few have focused on combination formulas. Thus, research on the meridian-tropism theory of traditional Chinese medicine is separated from the clinical applications of traditional Chinese medicine, and the results cannot reveal the entire scientific connotation of the meridian tropism of processed Chinese medicine. Radix bupleuri–Radix paeoniae alba is a common drug pair for soothing the liver and regulating the spleen with known hepatoprotective effects. Our previous studies have shown that the chemical substances in Radix bupleuri and Radix paeoniae alba quantitatively and qualitatively change after stir baking with vinegar. With the enhanced effect of soothing the liver and regulating the spleen, this formula intervenes with tryptophan metabolism in the microenvironment and controls the KCs regulation effect by downregulating IDO1 and upregulating GCN2, thereby exerting an antihepatic-fibrosis effect. However, the material basis and mechanism of stir baking with vinegar for improved activity have not yet been clarified. In this study, using Radix bupleuri–Radix paeoniae alba as a representative, a target-fishing active ingredient/metabolite-HSCCC×HPLC separation and preparation mode is used to discuss the mechanism of Radix bupleuri-Radix paeoniae alba to enhance the regulation of the IDO1/GCN2 pathway and intervene with the immune microenvironment of hepatic fibrosis through gene recombination, cellular immunobiology, and drug metabolism. Based on the target fishing of active ingredients of liver cells, the material basis of stir baking with vinegar for enhancing antihepatic fibrosis is clarified. This work provides a new idea for research on the compatibility meridian tropism of traditional Chinese medicine and the design of antihepatic fibrosis drugs, thereby strongly promoting the development of the innovative theory of traditional Chinese Medicine.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1016/j.bioactmat.2022.11.001
发表时间:2023-05
期刊:BIOACTIVE MATERIALS
影响因子:18.9
作者:Shao, Meiyu;Wang, Yifan;Dong, Hongyan;Wang, Lu;Zhang, Xiaoqing;Han, Xin;Sang, Xianan;Bao, Yini;Peng, Mengyun;Cao, Gang
通讯作者:Cao, Gang
DOI:10.1016/j.pharmthera.2020.107791
发表时间:2021
期刊:Pharmacology & Therapeutics
影响因子:--
作者:Xin Han;YanLing Wu;Qiao Yang;Gang Cao
通讯作者:Gang Cao
DOI:10.1038/s42003-023-04473-2
发表时间:2023-02-16
期刊:Communications biology
影响因子:5.9
作者:
通讯作者:
DOI:10.1111/bph.15952
发表时间:2022
期刊:British Journal of Pharmacology
影响因子:--
作者:Min Hao;Xin Han;Zhouhui Yao;Han Zhang;Mengting Zhao;Mengyun Peng;Kuilong Wang;Qiyuan Shan;Xianan Sang;Xin Wu;Lu Wang;Qiang Lv;Qiao Yang;Yini Bao;Haodan Kuang;Hongyan Zhang;Gang Cao
通讯作者:Gang Cao
麸炒白芍通过IL-33/IL-13/IL-1R2信号轴调控支链氨基酸代谢抑制T细胞代谢编程改善过敏性哮喘的机制研究
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    51万元
  • 批准年份:
    2022
  • 负责人:
    曹岗
  • 依托单位:
盐炙车前子调节肠源性色氨酸代谢物/AHR/氧化应激途径发挥肾保护增效机制研究
  • 批准号:
    LZ22H280001
  • 项目类别:
    省市级项目
  • 资助金额:
    0.0万元
  • 批准年份:
    2021
  • 负责人:
    曹岗
  • 依托单位:
基于LGR4靶点和在线定向捕获的“山茱萸-白芍”酒炙配伍治疗类风湿关节炎物质基础和作用机制研究
  • 批准号:
    81773900
  • 项目类别:
    面上项目
  • 资助金额:
    57.0万元
  • 批准年份:
    2017
  • 负责人:
    曹岗
  • 依托单位:
基于“针捕集-肠道微生态学-代谢标志物”探讨白术芍药散治疗溃疡性结肠炎炮制增效机理
  • 批准号:
    81573602
  • 项目类别:
    面上项目
  • 资助金额:
    52.0万元
  • 批准年份:
    2015
  • 负责人:
    曹岗
  • 依托单位:
基于微透析及多光谱成像技术的白芍和白术饮片配伍治疗肝郁脾虚证机理研究
  • 批准号:
    81202918
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    24.0万元
  • 批准年份:
    2012
  • 负责人:
    曹岗
  • 依托单位:
国内基金
海外基金