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. 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. 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) kg, 100 mg / kg and 300 mg / kg) or tegaserod (1 mg / kg) were tested on 6 h fecal pellets output by freely fed mice. The ratio of wet to dry weight was calculated and used as a marker of fecal water content.RESULTS: Mangiferin 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-HT4) agonist tegaserod (81%) when compared to vehicle- treated control 2-adrenocorticoceptor 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 suggesting that 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.