Effects of momordica charantia fruit juice on experimental diabetes and its complications
Momordica charantia fruit is traditionally used as a vegetable in the Indian subcontinent and is claimed to have hypoglycaemic effects in human and experimental diabetes. The oral administration of M. charantia fruit juice was investigated for its effects in streptozotocin (STZ)-induced diabetes in rats. The results of this study have revealed that the fruit juice administration reduced the blood glucose levels, improved glucose tolerance and increased blood insulin levels and body weights in STZ-induced diabetes in rats. However, the treatment of fruit juice did not completely normalize these parameters as the values were still significantly different from those of age-matched controls. The systolic blood pressure was significantly increased in diabetic animals when compared to untreated diabetic rats. The treatment of Lvi. charantia to diabetic animals completely prevented such an increase as the values were not significantly different from that of age-matched controls. The administration of M charantia to STZ-induced diabetic rats also reduced the absorption of glucose by the brush border of small intestine. A similar reduction in glucose uptake by muscle cells in vitro was also observed. In an immunohistochemical study of the pancreas on number and distribution of endocrine cells, a significant increase in the number of insulin positive cells was observed in Lvi charantia treated-diabetic animals as compared with untreated diabetic rats. However, their number was still significantly less than that obtained for control animals. The effect of M charantia treatment on myelinated fibre abnormalities in the tibial nerve of STZ- induced diabetic and control rats was also investigated. The mean cross-sectional myelinated fibres area (p C 0.03), axonal area (p C 0.02) and myelin area (p < 0.04) including the mean maximum myelinated fibres area (p C 0.03) were significantly reduced in untreated diabetic animals when compared with age-matched controls. In the M. charatia treated diabetic animals, myelinated fibre area and myelin area were significantly greater than untreated diabetics (p C 0.05) and not significantly different from age-matched controls. The mean value for the maximum fibre area was also significantly greater than that of untreated diabetics (p< 0.05) and was not significantly different from that of age-matched controls. In summary, the administration of M. charantia normalised the structural abnormalities of peripheral nerves in experimental diabetes. The changes in STZ-induced diabetes related to oxidative stress and expression of P450 and GST isoenzymes was studied. The results indicated an increase in CYP4Adependent laurie acid hydroxylation in liver, kidney and the brain of STZ-diabetic rats. An increase in CYP2B-dependent aniline hydroxylation and CYP lA-dependent ethoxycoumarin-O-deethylase activities was also observed. A significant increase in aminopyrene-N-demethylase activity was observed only in rat kidney while there was a decrease in the liver and brain of diabetic rats. A significant increase in NADPHdependent lipid peroxidation (LPO) in kidney of diabetic rats was also observed. On the other hand, a decrease in hepatic LPO was seen during chronic diabetes. During diabetes an increased expression of CYP1AI, CYP2E1 and CYP4A2 proteins was also seen by western blot analysis. Mi charantia fruit juice feeding modulated the protein expression and catalytic activities in a tissue and isoenzyme specific manners. A marked decrease in hepatic glutathione (GSH)) content and glutathione Stransferase (GST) activity and an increase in brain OSH and GST activity was observed in diabetic rats. On the other hand, renal GST was markedly reduced while GSH content was moderately higher than that of control rats. Western blot and immunohistochemical analysis using specific antibodies have confirmed the tissue specific alterations in the expression of OST isoenzymes. M. charantia juice feeding, in general, reversed the effect of long tenn STZ-diabetes on the modulation of both P450-dependent monooxygenase activities and GSH-dependent oxidative stress related LPO and GST activities. These effects were found to be tissue specific and related to the modulation of various specific isoenzymes during diabetes. These results have suggested that the modulation of xenobiotic metabolism and oxidative stress in various tissues may be related to altered metabolism of endogenous substrates and hormonal status during diabetes. These findings reported in this thesis may have implications in elucidating the therapeutic use of M charantia in the management of diabetes mellitus.
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