Diabetes mellitus refers to the group of diseases that lead to high blood glucose levels due to defects in either insulin secretion or insulin action. Diabetes develops due to a diminished production of insulin (in type 1) or resistance to its effects (in type 2 and gestational). Both lead to hyperglycaemia, which largely causes acute signs of diabetes: excessive urine production, resulting compensatory thirst and increased fluid intake, blurred vision, unexplained weight loss, lethargy, and changes in energy metabolism.
The in-vitro antidiabetic activity of the both ethylacetate and aqueous extracts have been evaluated by measuring its α-amylase inhibitory activity and non-enzymatic glycosylation of haemoglobin.
α-amylase is an enzyme which converts starch to oligosaccharide. Inhibition of this enzyme can retard glucose absorption, and thereby can produce hypoglycaemic action.Glycosylated haemoglobin is a blood test to determine level of glycemic control. Blood glucose binds to haemoglobin through a process called glycosylation. The higher the blood sugar the more glucose binds to haemoglobin can be determined by using non-enzymatic glycosylation of haemoglobin test.
The results of both in-vitro study with alpha amylase and non-enzymatic glycosylation of haemoglobin exhibited potential inhibitory activity for the aqueous extract of plant Moringa pterygosperma and it was compared with standard acarbose and α-tocopherol .
Streptozotocin (STZ) is 1-methyl-l-nitrosourea attached to the carbon-2 position of glucose that causes β-cell necrosis and induces experimental diabetes in many animal models. It causes DNA strand breaks that induce the activation of poly-ADP-ribose synthetase followed by lethal nicotinamide adenine dinucleotide (NAD) depletion. Nicotinamide adenine dinucleotide causes activation of the poly ADP ribose synthase to repair the damaged DNA and protecting the decrease in the level of NAD and proinsulin thereby partially reversing the inhibition of insulin secretion to prevent the aggravation of experimental diabetes. This condition shows a number of features which are similar with type 2 diabetic mellitus (T2DM). Hence, based on this point of view, the hypoglycaemic activity of aqueous extracts of MPLE carried out on STZ and nicotinamide induced type 2 diabetic rats.
In streptozotocin and nicotinamide-induced type 2 diabetic mellitus, oral administration of aqueous extract of AEMP for 28 days showed a significant reduction in body weight in diabetic rats is due to excessive break down of tissue protein. Treatment with AEMP or gibenclamide improved body weight significantly inducing prevention of muscle wasting due to hyperglycaemic condition.
The percentage difference in body weight is large in control group compared with negative control group. In treatment group also increases the body weight compared with the diabetic control group.
The hypoglyamic activity of MPLE was compared with glibenclamide,a standard second generation hypoglycemic drug. Acute administration of sulfonyl urea
increases insulin release from the pancreas, Sulfonyl ureas such as gibenclamide have used for many years to treat diabetes, to stimulate insulin secretion from ß-cells principally by inhibiting ATP-sensitive K+ (KATP) channels in the plasma membrane. Further, it is known that sulfonylureas have a direct effect on ß-cell exocytosis and that effect is mediated by a mechanism that does not involve direct activation of protein kinase-C, which place a major role in controlling the ß-cell potential. The inhibition of ATP sensitive channels leads to membrane depolarization, activating Ca channels, increased calcium influx, a rise in cytosolic (Ca2+) and there by insulin release. Oral administration of MPLE and glibenclamide to the STZ and nicotinamide-induced diabetic rats decreased the blood glucose levels.
The extent of complications of diabetes appears to correlate with elevated blood glucose concentrations and it is widely thought that excessive glucose is the major cause of tissue injury. Indeed, several mechanism exists by which glucose and other sugars can damage tissues which include the enzyme glucokinase which converts glucose to glucose-6-phosphate.
Increase in concentration of total cholesterol, triglycerides, LDL and VLDL and decreased HDL is observed in diabetes untreated rats. Hyperlipidemia is a recognized consequence of diabetes mellitus. Administration of AEMP and glibenclamide normalized serum lipids, secondary to the diabetes state. Diabetes induced hyperlipidaemia is attributable of excess mobilization of fat from the adipose tissue due to the under utilization of glucose.
Increase in ALT, AST and ALP are the predictors of diabetes and are common sign of liver disease. In streptozotocin-nicotinamide induced type 2 diabetic, rats increase in serum SGOT, SGPT and ALP level may be due to the leakage of these enzymes from liver cytosol into blood stream as a result of the hepatotoxic effect of STZ. Treatment with aqueous extract of MPLE decreased the levels of ALT, AST and ALP in diabetic animals, which indicates that the extract tends to prevent liver damage in diabetes by maintaining integrity of plasma membrane, thereby suppressing the leakage of enzymes through membrane. Insulin deprivation in diabetic state causes a profound increase in protein catabolism.
In this study, fall in plasma total protein and rise in serum urea, creatinine and blood urea levels were observed in diabetic rats. Urea and creatinine in the serum are significant markers to detect the renal dysfunction, might be due to increased protein catabolism in the body. Accumulation of urea in experimental diabetes may due to the enhanced breakdown of both liver and plasma proteins. The decrease in serum urea and creatinine levels on treatment with extract indicated that the extract has prevented the progression of renal damage in diabetic rats.
Free radical have been implicated in the causation of several disorders, which includes diabetes and the agents that scavenge free radicals may have great potential in ameliorating these disease processes. Antioxidants play a important role in protecting the human body against damage ROS. Increased oxidative stress has been postulated in the diabetic state. Oxidative stress in diabetes co exists with a reduction in the antioxidant status, which can increase the deleterious effects of free radicals.
Generation of these free radicals in diabetes mellitus reacts with lipids causing lipid peroxidation, resulting in the release of products such as malondialdehyde, hydroperoxide and hydroxyl radicals. The oxidative stress in diabetes decreases the antioxidant status. SOD, CAT, GSSH and GPx are enzymatic antioxidants and non enzymatic antioxidant like GSH is plays an important role in protecting cells from being exposed to oxidative damage by direct elimination of reactive oxygen species (ROS). CAT and SOD are considered primary enzymes since they are involoved in the direct elimination of ROS. SOD is an important defence enzyme which catalyses the dismutation of superoxide radical and CAT is a haemoprotein which catalyses the reduction of H2O and protects the tissue from hydroxyl radicals. GPX, a selenium containing enzyme present in significant concentration detoxifies H2O2 to H2O through the oxidation of reduced glutathione. The reduced activity of SOD, CAT, GPX, GSSH, GSH in the liver, kidney, pancreas during diabetes is a result of deleterious effects which results in the accumulation of superoxide anion radicals and H2O2. The activity of enzymatic and non enzymatic antioxidants are increased significantly in AEMP treated animals (P<0.01).
Marked increase in the concentration of MDA was observed in the liver, kidney, pancreas of diabetes rats. AEMP and glibenclamide tends to bring the increased concentration of lipid peroxidation products to near normal level.
In conclusion it maybe stated that, there occurs a significant (P<0.01) decrease in the hyperglycaemic state after the administration of AEMP which reduce the severity of oxidative and acuity of hyperglycaemia, a process that closely linked to glucose oxidation and formation of free radicals. Our results suggested that AEMP has more favourable reduction in lipid level in STZ and nicotinamide - induced diabetic rats, compared with glibenclamide as well as regeneration of ß-cells of pancreas. The present study suggests that Moringa pterygosperma can be successfully utilized for the management of diabetes due to their anti-hyperglycaemic action. Further studies on the nature of functional group involved and isolation of active constituents would enlighten the exact mechanism and thus help to rationalize their use in the treatment of diabetes more effectively
