Mahuannin B an adenylate cyclase inhibitor attenuates hyperhidrosis via suppressing β 2 -adrenoceptor/cAMP signaling pathway

• Published in: Phytomedicine (Stuttgart) 2017-07, Vol.30, p.18-27
• Main Authors: Wang, Zengyong, Cui, Yu, Ding, Guoyu, Zhou, Mengge, Ma, Xiaoyao, Hou, Yuanyuan, Jiang, Min, Liu, Dailin, Bai, Gang
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclase Inhibitors - chemistry; Adenylyl Cyclase Inhibitors - pharmacology; Adrenergic beta-2 Receptor Antagonists - chemistry; Adrenergic beta-2 Receptor Antagonists - pharmacology; Alkaloids - chemistry; Alkaloids - pharmacology; Animals; Chromatography, High Pressure Liquid; Cyclic AMP - metabolism; Drug Evaluation, Preclinical - methods; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Ephedra - chemistry; Ephedra sinica - chemistry; Ephedrine - pharmacology; Flavonoids - chemistry; Flavonoids - pharmacology; Male; Mice; Molecular Docking Simulation; Receptors, Adrenergic; Receptors, Adrenergic, beta-2 - metabolism; Signal Transduction - drug effects; Species Specificity; Sweating - drug effects
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2017.03.002

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.