Journal of Ethnopharmacology 128 (2010) 679–684 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm Antitussive and central respiratory depressant effects of Stemona tuberosa Yan-Tong Xu a , Pang-Chui Shaw b,c , Ren-Wang Jiang c,d , Po-Ming Hon c , Yiu-Man Chan a , Paul Pui-Hay But a,c,∗ a Department of Biology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China b Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China c Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China d Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou, PR China article info Article history: Received 10 November 2009 Received in revised form 8 January 2010 Accepted 11 February 2010 Available online 26 February 2010 Keywords: Stemona tuberosa Alkaloids Antitussive Central respiratory depressant abstract Aims of the study: Stemona alkaloids with distinctly different chemical skeletons are recently reported as the active components in the antitussive herb Baibu derived from the root-tubers of Stemona tuberosa. This study aims to determine if alkaloids of this herb contribute equally to the antitussive functions, act on the same sites of cough reflex, and play any role in inducing central respiratory depressant effects. Materials and methods: Antitussive potency of four major alkaloids was evaluated on guinea pigs with citric acid aerosol to induce cough. The action sites of the alkaloids on cough reflex pathway were tested with electrical stimulation of the superior laryngeal nerve in guinea pigs. The central respiratory effects of croomine were also tested on guinea pigs. Results: Croomine, neotuberostemonine and stemoninine showed similar antitussive potency, while tuberostemonine showed much weaker antitussive potency. Neotuberostemonine, tuberostemonine and stemoninine acted on the peripheral cough reflex pathway, while croomine acted on the central part. Croomine also showed obvious central respiratory depressant effects. Conclusions: The four major Stemona alkaloids in Stemona tuberosa do not contribute equally to antitussive potency in guinea pigs. Neotuberostemonine, tuberostemonine and stemoninine target on peripheral cough reflex pathway. Croomine acts on central sites in the cough reflex pathway and demonstrates central respiratory depressant effects, which can partly account for the adverse reactions reported for the herb. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The root-tubers of Stemona tuberosa Loureiro (Stemonaceae) is known as ‘Baibu’ in traditional Chinese medicine. It first appeared in the herbal ‘Additional Records of Famous Physicians’ (Mingyi Bielu), which was compiled in the 6 th century A.D. According to this herbal, Baibu is indicated for treating cough and has mild toxicity (Jiangsu New Medical College, 1977; Perry and Metager, 1980; But, 1996; Cong and Xu, 1997; Pharmacopoeia Commission of the People’s Republic of China, 2005). Recent studies have demonstrated that alkaloids are the antitussive components in this herb (Chung et al., 2003; Xu et al., 2006; Lin et al., 2006, 2008a,b; Zhou et al., 2009). Stemona alkaloids are unique in molecular architecture. They can be divided into eight groups according to their structural features (Pilli et al., 2005) or three skeleton types based on biosynthetic considerations (Greger, 2006; Schinnerl et al., 2007). ∗ Corresponding author at: Department of Biology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China. Tel.: +852 9366 0328; fax: +852 2603 5646. E-mail address: paulbut@hotmail.com (P.P.-H. But). Chung et al. (2003) first reported that neotuberostemonine and related stenine-type Stemona alkaloids from Stemona tuberosa exhibited antitussive potency comparable to codeine but not involving opioid receptors in guinea pigs. More detailed analy- ses of the total alkaloids from different populations of Stemona tuberosa revealed that there are four chemical types featured by the major components neotuberostemonine, tuberostemo- nine, croomine and stemoninine (Jiang et al., 2002, 2006a,b; Xu et al., 2006; Zhou et al., 2006)(Fig. 1). Neotuberostemonine was found present in only one of the four chemical types (Xu et al., 2006). A follow-up study was made on the intragastric applications of the crude alkaloid fractions from samples repre- senting the four chemical types of Stemona tuberosa. The results demonstrated that all four chemical types expressed different degrees of antitussive properties, and thus suggested that total Stemona alkaloid fractions containing tuberostemospironine-type and stemonamide-type alkaloids other than stenine-type alkaloids could also contribute to antitussive functions (Xu et al., 2006). This interpretation was supported by Lin et al. (2006, 2008a,b), who con- firmed that stemoninine of stemonamide-type and croomine of tuberostemospironine-type alkaloids expressed antitussive func- 0378-8741/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2010.02.018