Li Siming, Li Xiaoling, Wang HeMeng, Jia Xinhang, Mao Haoyang, Dong Fangxin, Zhao Tingting, Gao Yuan, Zhang Chen, Bai Ruisong, Liu Ruihao, Yan Lijun, Ji Yubin, Zhang Na, Wang Wenfei
School of Pharmacy, Harbin University of Commerce, Harbin, China.
College of Life Sciences, Tarim University, Alar, China.
Front Pharmacol. 2022 Jul 22;13:895724. doi: 10.3389/fphar.2022.895724. eCollection 2022.
JinQi Jiangtang tablet (JQJTT) is a Chinese patent medicine that has been shown to be beneficial for patients with diabetes both preclinically and clinically; however, the molecular mechanism underlying the effects of JQJTT remains unclear. In this study, surface plasmon resonance fishing was employed to identify JQJTT constituent molecules that can specifically bind to fibroblast growth factor receptor 1 (FGFR1), leading to the retrieval of palmatine (PAL), a key active ingredient of JQJTT. and experiments demonstrated that PAL can significantly stimulate FGFR1 phosphorylation and upregulate glucose transporter type 1 (GLUT-1) expression, thereby facilitating glucose uptake in insulin resistance (IR) HepG2 cells as well as alleviating hyperglycemia in diabetic mice. Our results revealed that PAL functions as an FGFR1 activator and that the hypoglycemic effect of JQJTT is partially dependent on the PAL-induced activation of the FGFR1 pathway. In addition, this study contributed to the understanding the pharmacodynamic basis and mechanism of action of JQJTT and provided a novel concept for future research on PAL.
津杞降糖片(JQJTT)是一种中成药,临床前和临床研究均表明其对糖尿病患者有益;然而,JQJTT作用的分子机制仍不清楚。在本研究中,采用表面等离子体共振筛选技术来鉴定JQJTT中能够特异性结合成纤维细胞生长因子受体1(FGFR1)的成分分子,从而筛选出JQJTT的关键活性成分巴马汀(PAL)。实验表明,PAL可显著刺激FGFR1磷酸化并上调1型葡萄糖转运蛋白(GLUT-1)的表达,从而促进胰岛素抵抗(IR)HepG2细胞摄取葡萄糖,并减轻糖尿病小鼠的高血糖症状。我们的研究结果表明,PAL作为FGFR1激活剂发挥作用,JQJTT的降糖作用部分依赖于PAL诱导的FGFR1通路激活。此外,本研究有助于理解JQJTT的药效学基础和作用机制,并为今后对PAL的研究提供了新的思路。