基于靶点“钩钓”策略的首荟通便胶囊肠道直接作用靶点鉴定Identification of intestine direct targets of Shouhui Tongbian Capsules using "target fishing" strategy
郭强;姚璐;刘忠;姚景春;屠鹏飞;曾克武;
GUO Qiang;YAO Lu;LIU Zhong;YAO Jing-chun;TU Peng-fei;ZENG Ke-wu;State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University;State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co.,Ltd.;
摘要(Abstract):
基于靶点"钩钓"策略鉴定首荟通便胶囊发挥润肠通便作用的直接药理靶点,探索靶点相关药理学信号通路,揭示润肠通便机制。首先制备键合首荟通便胶囊药材总提取物的磁性固相微球,然后从大鼠肠道总蛋白裂解液中捕获直接作用靶点蛋白,并通过高分辨质谱进行鉴定,最后利用Cytoscape软件进行通路富集分析。共计发现138个首荟通便胶囊的潜在作用靶点蛋白。通过Cytoscape软件进行通路富集分析发现这些靶蛋白主要与三羧酸循环,嘧啶代谢,硫代谢,脂肪酸降解,丙氨酸、天冬氨酸和谷氨酸代谢,精氨酸和脯氨酸代谢,缬氨酸、亮氨酸和异亮氨酸降解,β-丙氨酸代谢这8条信号通路相关。以上结果表明,首荟通便胶囊主要通过作用于三羧酸循环等多个通路的138个靶点蛋白,进而发挥促进肠道动力学、抗炎、改善肠道细胞屏障功能、改善肠道水分泌、改善肠道菌群等多种作用,最终发挥润肠通便的临床疗效。
"Target fishing" strategy was used to investigate the direct targets and mechanism of Shouhui Tongbian Capsules on relaxing bowel. Magnetic beads cross-linked with the chemical constituents from Shouhui Tongbian Capsules were prepared. The potential target proteins were captured from the total protein lysates of rat intestine using the beads. The captured proteins were further identified by LC-MS/MS, and the associated pathways were analyzed by Cytoscape. Results showed that 138 potential target proteins were identified, which were involved in eight signaling pathways, including tricarboxylic acid cycle, pyrimidine metabolism, sulfur metabolism, fatty acid degradation, alanine/aspartate/glutamate metabolism, arginine/proline metabolism, valine/leucine/isoleucine degradation, and β-alanine metabolism. Taken together, Shouhui Tongbian Capsules may exert relaxing bowel effect by acting on multiple signaling pathways to promote intestinal gurgling, inhibit inflammation, as well as improve intestinal barrier function, intestinal water secretion, and intestinal flora.
关键词(KeyWords):
便秘;首荟通便胶囊;润肠通便;靶点鉴定;三羧酸循环
constipation;Shouhui Tongbian Capsules;relaxing bowel;target identification;tricarboxylic acid cycle
基金项目(Foundation): 国家自然科学基金项目(81973505,81773932)
作者(Author):
郭强;姚璐;刘忠;姚景春;屠鹏飞;曾克武;
GUO Qiang;YAO Lu;LIU Zhong;YAO Jing-chun;TU Peng-fei;ZENG Ke-wu;State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University;State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co.,Ltd.;
Email:
DOI: 10.19540/j.cnki.cjcmm.20201125.403
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- 便秘
- 首荟通便胶囊
- 润肠通便
- 靶点鉴定
- 三羧酸循环
constipation - Shouhui Tongbian Capsules
- relaxing bowel
- target identification
- tricarboxylic acid cycle
- 郭强
- 姚璐
- 刘忠
- 姚景春
- 屠鹏飞
- 曾克武
GUO Qiang- YAO Lu
- LIU Zhong
- YAO Jing-chun
- TU Peng-fei
- ZENG Ke-wu
- State Key Laboratory of Natural and Biomimetic Drugs
- School of Pharmaceutical Sciences
- Peking University
- State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine
- Lunan Pharmaceutical Group Co.
- Ltd.
- 郭强
- 姚璐
- 刘忠
- 姚景春
- 屠鹏飞
- 曾克武
GUO Qiang- YAO Lu
- LIU Zhong
- YAO Jing-chun
- TU Peng-fei
- ZENG Ke-wu
- State Key Laboratory of Natural and Biomimetic Drugs
- School of Pharmaceutical Sciences
- Peking University
- State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine
- Lunan Pharmaceutical Group Co.
- Ltd.