Mangiferin,a natural xanthone,accelerates gastrointestinal transit in mice involving cholinergic mechanism

AIM： To investigate the effects of mangiferin on gas- trointestinal transit （GIT） in normal and constipated mice, together with the possible mechanism.METHODS： Intragastrically-administered charcoal mealwas 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 char- coal 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 pharma- cological 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-hydroxytrypta- mine4 （5-H%） agonist tegaserod （81%） when compared to vehicle-treated control （63%）. Co-administered man- giferin （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 ~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 pel- lets （59.20%±1.09% vs 51.44%±1.19% of control, P 〈 0.05）, mangiferin evidenced no such effect, indi-cating 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 choliner- gic physiological mechanism.

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 mealwas 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 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,indi-cating 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.