Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 7, 2012; 18(25): 3207-3214
Published online Jul 7, 2012. doi: 10.3748/wjg.v18.i25.3207
Mangiferin, a natural xanthone, accelerates gastrointestinal transit in mice involving cholinergic mechanism
Talita Cavalcante Morais, Synara Cavalcante Lopes, Karine Maria Martins Bezerra Carvalho, Bruno Rodrigues Arruda, Francisco Thiago Correia de Souza, Maria Teresa Salles Trevisan, Vietla Satyanarayana Rao, Flávia Almeida Santos
Talita Cavalcante Morais, Synara Cavalcante Lopes, Karine Maria Martins Bezerra Carvalho, Bruno Rodrigues Arruda, Francisco Thiago Correia de Souza, Maria Teresa Salles Trevisan, Vietla Satyanarayana Rao, Flávia Almeida Santos, Department of Physiology and Pharmacology, Brazilian Semi-Arid Institute of Biomedicine, Faculty of Medicine, Federal University of Ceará, Fortaleza 60430-270, Brazil
Karine Maria Martins Bezerra Carvalho, Post-Graduate Programme in Medical Sciences, Faculty of Medicine, Federal University of Ceará, Fortaleza 60430-140, Brazil
Francisco Thiago Correia de Souza, Maria Teresa Salles Trevisan, Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza 60451-970, Brazil
Author contributions: Morais TC designed the research; Morais TC, Lopes SC, Carvalho KMMB and Arruda BR contributed to the experimental part; Rao VS and Santos FA wrote the paper; de Souza FTC and Trevisan MTS isolated the compound mangiferin.
Supported by National Council of Technological and Scientific Development (CNPq); Ceará Foundation for the Support of Scientific and Technological Development of the Ceará State (FUNCAP), Brazil
Correspondence to: Vietla Satyanarayana Rao, Associate Professor of Pharmacology, Department of Physiology and Pharmacology, Brazilian Semi-Arid Institute of Biomedicine, Faculty of Medicine, Federal University of Ceará, Rua Cel. Nunes de Melo, 1127, Rodolfo Teófilo, Fortaleza 60430-270, Brazil. viet_rao@yahoo.com.br
Telephone: +55-85-33668341 Fax: +55-85-33668333
Received: November 30, 2011
Revised: April 25, 2012
Accepted: May 6, 2012
Published online: July 7, 2012
Abstract

AIM: To investigate the effects of mangiferin on gastrointestinal transit (GIT) in normal and constipated mice, together with the possible mechanism.

METHODS: Intragastrically-administered charcoal meal was used to measure GIT in overnight starved Swiss mice. In the first experiments, mangiferin (3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg, po) or tegaserod (1 mg/kg, ip) were administered 30 min before the charcoal meal to study their effects on normal transit. In the second series, mangiferin (30 mg/kg) was tested on delayed GIT induced by several different pharmacological agonists (morphine, clonidine, capsaicin) or antagonists (ondansetron, verapamil, and atropine) whereas in the third series, mangiferin (30 mg/kg, 100 mg/kg and 300 mg/kg) or tegaserod (1 mg/kg) were tested on 6 h fecal pellets outputted by freely fed mice. The ratio of wet to dry weight was calculated and used as a marker of fecal water content.

RESULTS: Mangiferin administered orally significantly (P < 0.05) accelerated GIT at 30 mg/kg and 100 mg/kg (89% and 93%, respectively), similarly to 5-hydroxytryptamine4 (5-HT4) agonist tegaserod (81%) when compared to vehicle-treated control (63%). Co-administered mangiferin (30 mg/kg) totally reversed the inhibitory effect of opioid agonist morphine, 5-HT3-receptor antagonist ondansetron and transient receptor potential vanilloid-1 receptor agonist capsaicin on GIT, but only to a partial extent with the GIT-delay induced by α2-adrenoceptor agonist clonidine, and calcium antagonist verapamil. However, co-administered atropine completely blocked the stimulant effect of mangiferin on GIT, suggesting the involvement of muscarinic acetylcholine receptor activation. Although mangiferin significantly enhanced the 6 h fecal output at higher doses (245.5 ± 10.43 mg vs 161.9 ± 10.82 mg and 227.1 ± 20.11 mg vs 161.9 ± 10.82 mg of vehicle-treated control, at 30 and 100 mg/kg, P < 0.05, respectively), the effect of tegaserod was more potent (297.4 ± 7.42 mg vs 161.9 ± 10.82 mg of vehicle-treated control, P < 0.05). Unlike tegaserod, which showed an enhanced water content in fecal pellets (59.20% ± 1.09% vs 51.44% ± 1.19% of control, P < 0.05), mangiferin evidenced no such effect, indicating that it has only a motor and not a secretomotor effect.

CONCLUSION: Our data indicate the prokinetic action of mangiferin. It can stimulate the normal GIT and also overcome the drug-induced transit delay, via a cholinergic physiological mechanism.

Keywords: Mangiferin; Glucosylxanthone; Gastrointestinal transit; Prokinetic action; Cholinergic mechanism