Zhang Xiao-Wen, Zheng Shu-Ze, Li Xin, Sun Cheng-Hong, Zeng Ke-Wu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Beijing 100191, China.
State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co., Ltd. Linyi 276006, China.
Zhongguo Zhong Yao Za Zhi. 2021 Feb;46(3):526-531. doi: 10.19540/j.cnki.cjcmm.20201209.401.
Mechanism study was performed to explore how Shouhui Tongbian Capsules promotes energy metabolism of gastrointestinal stromal cells. In this study, gastrointestinal stromal cells line GIST-882 was used as the model to explore energy metabolism regulation effects of Shouhui Tongbian Capsules extract(10, 20, 50 and 100 μg·mL~(-1)) by measuring the cell proliferation, ATP level, mitochondrial membrane potential, and mitochondrial isocitrate dehydrogenase activity. Meanwhile, Western blot was used to detect the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Our results showed that Shouhui Tongbian Capsules promoted cell proliferation and increased ATP level of gastrointestinal stromal cells. In addition, Shouhui Tongbian Capsules obviously improved mitochondrial structural integrity, and increased mitochondrial membrane potential in GIST-882 cells. Mechanism study revealed that Shouhui Tongbian Capsules increased mitochondrial isocitrate dehydrogenase activity and up-regulated the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Collectively, our study indicated that Shouhui Tongbian Capsules promoted the energy metabolism for gastrointestinal stromal cells proliferation by activating mitochondrial isocitrate dehydrogenase to induce ATP production, as well as activating SCF/c-Kit and CDK2/cyclin A signaling pathways.
进行机制研究以探索寿辉通便胶囊如何促进胃肠道间质细胞的能量代谢。在本研究中，以胃肠道间质细胞系GIST - 882为模型，通过测量细胞增殖、ATP水平、线粒体膜电位和线粒体异柠檬酸脱氢酶活性，探讨寿辉通便胶囊提取物（10、20、50和100μg·mL⁻¹）对能量代谢的调节作用。同时，采用蛋白质免疫印迹法检测SCF/c - Kit和CDK2/cyclin A信号通路的蛋白表达。结果显示，寿辉通便胶囊可促进胃肠道间质细胞增殖并提高其ATP水平。此外，寿辉通便胶囊明显改善了线粒体结构完整性，并增加了GIST - 882细胞的线粒体膜电位。机制研究表明，寿辉通便胶囊增加了线粒体异柠檬酸脱氢酶活性，并上调了SCF/c - Kit和CDK2/cyclin A信号通路的蛋白表达。总体而言，本研究表明寿辉通便胶囊通过激活线粒体异柠檬酸脱氢酶以诱导ATP产生，以及激活SCF/c - Kit和CDK2/cyclin A信号通路，促进胃肠道间质细胞增殖的能量代谢。
