Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu Province, China.
Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Sci Rep. 2017 Jun 19;7(1):3828. doi: 10.1038/s41598-017-03201-1.
As recorded in Traditional Chinese Medicine (TCM) theory, Gancao (Glycyrrhizae Radix et Rhizoma) could weaken the pharmacological effect or increase the toxicity of Yuanhua (Genkwa Flos). However, the theory has been suspected due to lack of evidence. Here, we investigate whether Gancao could weaken Yuanhua's diuretic effect, if so, which chemicals and which targets may be involved. Results showed that Yuanhua exerted diuretic effect through down-regulating renal AQP 2, without electrolyte disturbances such as K loss which has been observed as side-effect of most diuretics. Gancao had no diuretic effect, but could impair Yuanhua's diuretic effect through up-regulating renal AQP 2. Glycyrrhetinic acid (GRA) in Gancao could up-regulate AQP 2 and counteract the AQP 2 regulation effect of Yuanhuacine (YHC) and Ginkwanin (GKW) in Yuanhua. Network pharmacology method suggested that YHC, GKW and GRA could bind to MEK1/FGFR1 protein and influence ERK-MAPK pathway, which was verified by Western blotting. This study supports TCM theory and reminds that more attention should be paid to the safety and efficacy problems induced by improper combination between herbs. Moreover, we suggested that promising diuretics with less side effects can be developed from Chinese Medicines such as Yuanhua.
在中医理论中，甘草（Glycyrrhizae Radix et Rhizoma）可能会减弱芫花（Genkwa Flos）的药理作用或增加其毒性。然而，由于缺乏证据，该理论一直受到质疑。在这里，我们研究了甘草是否会减弱芫花的利尿作用，如果是这样，哪些化学成分和哪些靶点可能涉及其中。结果表明，芫花通过下调肾脏 AQP2 发挥利尿作用，不会像大多数利尿剂那样引起电解质紊乱，如 K 丢失。甘草本身没有利尿作用，但可以通过上调肾脏 AQP2 来损害芫花的利尿作用。甘草中的甘草酸（GRA）可以上调 AQP2，并抵消芫花中的芫花辛（YHC）和银杏素（GKW）对 AQP2 的调节作用。网络药理学方法表明，YHC、GKW 和 GRA 可以与 MEK1/FGFR1 蛋白结合，并影响 ERK-MAPK 通路，这一结果通过 Western blot 得到了验证。本研究支持中医理论，并提醒人们应更加关注草药不当组合引起的安全性和疗效问题。此外，我们建议可以从芫花等中药中开发出副作用更小的有前途的利尿剂。
