Zhang Chenning, Liu Chuanxin, Wu Hao, Wang Jiaqi, Sun Yu, Liu Runhua, Li Tianyi, Yu Xue, Geng Di, Sun Yi-Kun
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Front Pharmacol. 2021 Apr 30;12:654807. doi: 10.3389/fphar.2021.654807. eCollection 2021.
Shuangxia decoction is an effective traditional Chinese medicine formula for treating insomnia. Up to now, there has not been any report about the effective substances. An omics data processing method based on mass spectrometry technology is used to explore the chemical composition changes of Shuangxia decoction, the components absorbed into the blood and brain, and to explore the anti-insomnia mechanism based on molecular docking technology. Forty-nine chemical components in Shuangxia decoction have been identified, and 51 new components generated by co-decoction have been discovered. It was found that 7,404 compounds of Shuangxia decoction were absorbed into the blood. Forty kinds of known compounds were quickly identified, and 15 new compounds generated by co-decoction were also found to be absorbed into the blood. By using UPLC-MS/MS method, it was confirmed that 10 compounds were absorbed into the blood and 9 compounds were absorbed into the brain. Furthermore, it is found that rosmarinic acid is mainly distributed in the hypothalamus and striatum, and caffeic acid is mainly distributed in the hypothalamus, striatum, and hippocampus. Molecular docking results showed rosmarinic acid, danshensu, and HMLA with GABA receptor have excellent binding characteristics, even surpassing the proligand. Danshensu and HMLA with dopamine D receptor also showed good binding energy. Our findings will help to further confirm the mechanism of Shuangxia decoction for relieving insomnia, and we also establish a novel data processing method for supplementing the mechanism of the efficacy of other traditional Chinese medicine formula.
双夏汤是一种治疗失眠的有效中药方剂。迄今为止，尚未有关于其有效成分的报道。采用基于质谱技术的组学数据处理方法，探究双夏汤的化学成分变化、吸收入血和脑内的成分，并基于分子对接技术探究其抗失眠机制。已鉴定出双夏汤中的49种化学成分，发现共煎产生51种新成分。发现双夏汤有7404种化合物吸收入血。快速鉴定出40种已知化合物，还发现共煎产生的15种新化合物也吸收入血。采用超高效液相色谱-串联质谱法（UPLC-MS/MS）证实有10种化合物吸收入血，9种化合物吸入脑内。此外，发现迷迭香酸主要分布于下丘脑和纹状体，咖啡酸主要分布于下丘脑、纹状体和海马体。分子对接结果表明，迷迭香酸、丹参素和HMLA与GABA受体具有良好的结合特性，甚至超过先导配体。丹参素和HMLA与多巴胺D受体也显示出良好的结合能。我们的研究结果将有助于进一步证实双夏汤缓解失眠的机制，同时也建立了一种新的数据处理方法，以补充其他中药方剂疗效机制的研究。
