Antidiabetic and hepatoprotective effects of moringa oleifera leaf extras in streptozotocin-induced diabetes in rats.
Muzumbukilwa, Willy Tambwe.
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Diabetes Mellitus is one of the major causes of degenerative diseases worldwide. Long term complications of diabetes include hepatic injury characterized by cirrhosis, inflammation, apoptosis, and microvascular and macrovascular aberrations. Mechanisms by which diabetes induces liver damage include the development of lipotoxicity-induced mitochondrial dysfunction and activation of inflammatory pathways that lead to progressive liver damage. Previous studies have reported that the leading cause of death in patients with diabetes mellitus is chronic liver disease. The liver is a metabolically active organ involved in many vital life functions. It performs many activities that are critical for survival. Due to its important activities, the liver is exposed to a number of insults and is one of the body's organs most subject to injury. Despite considerable progress in modern medicine, there are very few therapeutic agents that can protect the liver from hyperglycemia-induced oxidative damage and restore normal liver functions. As a result, the search for novel therapies that would be cheaper and effective in the management of liver diseases is paramount. Moringa oleifera (MO) is a multipurpose plant traditionally used for its medicinal and nutritional properties in many countries, especially in Durban, KwaZulu-Natal/ South Africa where the material for this study has been harvested. It has been shown to possess antihyperglycemic, antioxidant and anti-inflammatory properties and could possibly prevent liver injury. This study, therefore, investigated whether MO leaf extracts could mitigate hepatotoxicity associated with diabetes mellitus. Methods Male Wistar rats (250-300 g) were divided into six groups (n=7). Group A was orally treated daily with 3.0 ml/kg body weight (BW) of distilled water; group C was similarly treated with MO (500 mg/kg/BW) daily. Groups B, D, E, and F were rendered diabetic by a single intraperitoneal injection of streptozotocin (STZ) (45 mg/kg/BW in 0.1M citrate buffer, pH4.5). Diabetes was confirmed 3 days later. Additionally, group D was treated with subcutaneous insulin (2 U/kg/BW, bid) while groups E and F were orally treated daily with MO 250 mg/kg/BW and 500 mg/kg/BW, respectively. Glucose tolerance tests (GTT) were done on day 47 of the animal treatment. After an overnight fast for 8 hours, rats in all groups were intraperitoneally dosed with a D-glucose solution (3.0 g/kg BW) in 0.9% normal saline. This solution was prepared by dissolving 45 g of D-glucose anhydrous in 60 ml distilled water (0.75 g/ml). Blood glucose concentrations were measured by tail pricking at 0, 30, 60, 90, and 120 minutes, using glucometer (OneTouch select®; Lifescan Inc., Milpitas, California, USA). On day 54 of treatment, animals were sacrificed by halothane overdose. Blood was collected by cardiac puncture in heparinized tubes then separated into plasma and stored at -80˚C for further biochemical analysis. Livers were excised, snap-frozen in liquid nitrogen and similarly stored for histological analysis. Results: Diabetic animals had significantly (p<0.05) elevated Fasting Blood Glucose (FBG) and reduced insulin levels compared to controls. Treatment with either insulin or MO significantly (p<0.05) reduced FBG compared to non-treated diabetic rats. Treatment with 500 mg/kgBW significantly reduced FBG compared to treatment with 250 mg/kgBW. Calculated Areas-Under-the Curve (AUCs) from OGTT suggested that untreated diabetic rats exhibited glucose intolerance but treatment with either insulin or MO extracts significantly (p<0.05) reversed this. Liver function tests defined by Aspartate Aminotransaminase (ASAT), Alanine Aminotransaminase (ALAT),gamma-glutamyl aminotransaminase (GGT) and albumin were significantly (p<0.05) elevated in untreated diabetic group but treatment with either insulin or MO extracts significantly (p<0.05) reversed this. Treatment with 500 mg/kgBW of MO significantly (p<0.05) reduced GGT levels compared to treatment with 250 mg/kgBW. Untreated diabetic, unlike MO-treated rats, exhibited degeneration of hepatocytes and inflammatory cells infiltration with the fragmentation of the nucleus and cell lysis, necrotic hepatocytes, hepatic vein congestion, and vesicular cytoplasm compared to normal controls. Conclusion: This study has shown that methanolic leaf extracts of MO have dose-dependent antidiabetic effects. Liver function tests (ASAT, ALAT, GGT) and albumin were significantly elevated in untreated diabetic rats than those treated with MO extracts. This may justify the hepatoprotective effects of MO extracts in streptozotocin-induced diabetic rats.