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

α,β-amyrin, a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in rats

AIM: To study the benef icial effects of triterpene α,β-amyrin and the underlying mechanisms in an experimental pancreatitis model. METHODS: Acute pancreatitis was induced in five groups of rats (n = 8) by L-arginine (2 × 2.5 g/kg, intraperitoneal, 1 h apart) and 1 h later, they received a single oral dose of α,β-amyrin (10, 30 and 100 mg/kg),methylprednisolone (30 mg/kg) and vehicle (3% Tween 80). A saline (0.9% NaCl) treated group served as a normal control. Efficacy was assessed at 24 h by determination of serum levels of amylase, lipase and proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-6], pancreatic myeloperoxidase (MPO) activity, lipid peroxidation [thiobarbituric acid reactive substances (TBARS)], nitrate/nitrite levels, and the wet weight/body weight ratio. Tissue histology and the immunoreactivity for TNF-α and inducible nitric oxide synthetase (iNOS) were performed. RESULTS: α,β-amyrin and methylprednisolone treatments significantly (P < 0.05) attenuated the L-arginine-induced increases in pancreatic wet weight/body weight ratio, and decreased the serum levels of amylase and lipase, and TNF-α and IL-6, as compared to the vehicle control. Also, pancreatic levels of MPO activity, TBARS, and nitrate/nitrite were signifi cantly lower. Histological f indings and TNF-α and iNOS immunostaining further confirmed the amelioration of pancreatic injury by α,β-amyrin. CONCLUSION: α,β-amyrin has the potential to combat acute pancreatitis by acting as an anti-in? ammatory and antioxidant agent.