State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China.
Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental hazard, Logistics College of Chinese People's Armed Police Forces, Tianjin 300309, China.
Phytomedicine. 2017 Jul 1;30:18-27. doi: 10.1016/j.phymed.2017.03.002. Epub 2017 Mar 10.
Based on the traditional application of traditional Chinese Medicines (TCMs), Ephedra Herba (EH) is used to cure cold fever by inducing sweating, whereas Ephedra Radix (ER) is used to treat hyperhidrosis. Although they come from the same plant, Ephedra sinica Stapf, but have play opposing roles in clinical applications. EH is known to contain ephedrine alkaloids, which is the driver of the physiological changes in sweating, heart rate and blood pressure. However, the active pharmacological ingredients (APIs) of ER and the mechanisms by which it restricts sweating remain unknown.
The current work aims to discover the hidroschesis APIs from ER, as well as to establish its action mechanism.
UPLC-Q/TOF-MS, PCA, and heat map were utilized for identifying the differences between EH and ER. HPLC integrated with a β-adrenoceptor (β-AR) activity luciferase reporter assay system was used to screen active inhibitors; molecular docking and a series of biological assays centered on β-AR-related signaling pathways were evaluated to understand the roles of APIs.
The opposite effect on sweating of EH and ER can be attributed to the APIs of amphetamine-type alkaloids and flavonoid derivatives. Mahuannin B is an effective anti-hydrotic agent, inhibiting the production of cAMP via suppression of adenylate cyclase (AC) activity.
The effects of EH and ER on sweat and β-AR-related signaling pathway are opposite due to different alkaloids and flavonoids of APIs in EH and ER. The present work not only sheds light on the hidroschesis action of mahuannin B, but also presents a potential target of AC in the treatment of hyperhidrosis.
基于传统中药（TCM）的应用，麻黄（EH）用于发汗解表治疗感冒发热，而麻黄根（ER）用于治疗自汗盗汗。虽然它们来自同一种植物麻黄，但在临床应用中却起着相反的作用。EH 中含有麻黄碱类生物碱，是引起发汗、心率和血压生理变化的原因。然而，ER 的活性药理成分（APIs）及其限制出汗的机制尚不清楚。
本研究旨在发现 ER 中的止汗 API，并建立其作用机制。
采用 UPLC-Q/TOF-MS、PCA 和热图比较 EH 和 ER 之间的差异。HPLC 结合β-肾上腺素能受体（β-AR）活性荧光素酶报告基因检测系统筛选活性抑制剂；分子对接和一系列以β-AR 相关信号通路为中心的生物学实验评估 API 的作用。
EH 和 ER 在发汗方面的相反作用归因于安非他命型生物碱和黄酮类衍生物的 API。马兜铃宁 B 是一种有效的止汗剂，通过抑制腺苷酸环化酶（AC）活性抑制 cAMP 的产生。
EH 和 ER 对汗液和β-AR 相关信号通路的影响因 EH 和 ER 中不同的生物碱和黄酮类 API 而相反。本研究不仅阐明了马兜铃宁 B 的止汗作用机制，还为 AC 在治疗多汗症方面提供了一个潜在的靶点。
