Mangiferin, a natural xanthone, accelerates gastrointestinal transit in mice involving cholinergic mechanism.
OBJECTIVE
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-hydroxytryptamine(4) (5-HT(4)) 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-HT(3)-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 α(2)-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.


CONCLUSIONS
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.
Department of Physiology and Pharmacology, Brazilian Semi-Arid Institute of Biomedicine, Faculty of Medicine, Federal University of Ceará, Fortaleza 60430-270, Brazil.
Talita
T
Cavalcante Morais
Synara
S
Cavalcante Lopes
Karine Maria Martins
KM
Bezerra Carvalho
Bruno
B
Rodrigues Arruda
Francisco Thiago
FT
Correia de Souza
Maria Teresa
MT
Salles Trevisan
Vietla Satyanarayana
VS
Rao
Flávia
F
Almeida Santos
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D013997:Time Factors; D044004:Xanthones / Q000494:pharmacology*
D005765:Gastrointestinal Agents; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D044004:Xanthones; C013592:mangiferin; D001285:Atropine