Planta Med 2009; 75(13): 1393-1399
DOI: 10.1055/s-0029-1185743
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

β2-Adrenoceptor-Mediated Tracheal Relaxation Induced by Higenamine from Nandina domestica Thunberg

Muneo Tsukiyama1 , 2 [*] , Takuro Ueki1 , 3 [*] , Yoichi Yasuda2 , Hiroko Kikuchi2 , Tatsuhiro Akaishi1 , Hidenobu Okumura2 , Kazuho Abe1
  • 1Laboratory of Pharmacology, Faculty of Pharmacy and Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan
  • 2NOEVIR Co., Ltd., Kobe, Japan
  • 3TOKIWA Pharmaceutical Co., Ltd., Osaka, Japan
Further Information

Publication History

received Nov. 27, 2008 revised April 6, 2009

accepted April 14, 2009

Publication Date:
25 May 2009 (online)

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Abstract

The fruit of Nandina domestica Thunberg (ND, Berberidaceae) has been used to improve cough and breathing difficulties in Japan for many years, but very little is known about the constituent of ND responsible for this effect. We have recently reported that the crude extract from ND (NDE) inhibits histamine- and serotonin-induced contraction of isolated guinea pig trachea, and the inhibitory activity was not explained by nantenine, a well-known alkaloid isolated from ND. To explore other constituent(s) of NDE with tracheal smooth muscle relaxant activity, we fractionated NDE and assessed the pharmacological effects of the fractions using isolated guinea pig tracheal ring preparations. NDE was introduced into a polyaromatic absorbent resin column and stepwise eluted to yield five fractions, among which only the 40 % methanol fraction was active in relaxing tracheal smooth muscle precontracted with histamine. Further separation of the 40 % methanol fraction with high-performance liquid chromatography yielded multiple subfractions, one of which was remarkably active in relaxing histamine-precontracted trachea. Chemical analysis with a time-of-flight mass spectrometer and nuclear magnetic resonance spectrometer identified the constituent of the most active subfraction as higenamine, a benzyltetrahydroisoquinoline alkaloid. The potency and efficacy of the active constituent from NDE in relaxing trachea were almost equivalent to synthetic higenamine. In addition, the effect of the active constituent from NDE was competitively inhibited by the selective β2-adrenoceptor antagonist ICI 118,551. These results indicate that the major constituent responsible for the effect of NDE is higenamine, which probably causes the tracheal relaxation through stimulation of β2 adrenoceptors.