RESUMEN
This study investigated the anti-hyperglycemic action of mango seed kernel extract (MKE) and various mechanisms involved in its actions to improve pancreatic ß cells and hepatic carbohydrate metabolism in diabetic rats. An intraperitoneal injection of 60 mg/kg of streptozotocin (STZ) followed by 30 consecutive days of treatment with MKE (250, 500, and 1000 mg/kg body weight) was used to establish a study group of diabetic rats. Using liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) for identification, 26 chemical compounds were found in MKE and the high-performance liquid chromatography (HPLC) analysis of the MKE also revealed the existence of mangiferin, gallic acid, and quercetin. The results confirmed that in each diabetes-affected rat, MKE mitigated the heightened levels of fasting blood glucose, diabetic symptoms, glucose intolerance, total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C). As demonstrated by a remarkable increment in serum and pancreatic insulin, the diabetic pancreatic ß cell function was potentiated by treating with MKE. The effect of MKE on diabetic pancreatic apoptosis clearly reduced the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells, which was related to diminished levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and Bax and an increase in Bcl-xL protein expression. Furthermore, diabetes-induced liver damage was clearly ameliorated along with a notable reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and abnormal liver histology. By enhancing anti-oxidant superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, MKE alleviated diabetes-induced pancreatic and liver oxidative damage, as demonstrated by diminished levels of malondialdehyde. In minimizing the expression levels of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase-1 proteins in the diabetic liver, MKE also enhanced glycogen content and hexokinase activity. Collectively, these findings indicate that by suppressing oxidative and inflammatory processes, MKE exerts a potent anti-hyperglycemic activity in diabetic rats which serve to protect pancreatic ß cell apoptosis, enhance their function, and improve hepatic glucose metabolism.
Asunto(s)
Diabetes Mellitus Experimental , Hiperglucemia , Células Secretoras de Insulina , Mangifera , Ratas , Animales , Glucosa/metabolismo , Diabetes Mellitus Experimental/metabolismo , Espectrometría de Masas en Tándem , Glucemia/análisis , Antioxidantes/metabolismo , Hiperglucemia/metabolismo , Hígado , Apoptosis , Estrés Oxidativo , Extractos Vegetales/farmacología , Extractos Vegetales/metabolismo , Hipoglucemiantes/farmacología , Metabolismo de los Hidratos de Carbono , Colesterol/metabolismoRESUMEN
Diabetes mellitus is a metabolic disease affecting various organs, including the spleen and is characterized by chronic hyperglycemia. Oxidative and inflammatory stress are key mediators in the development of spleen damage caused by diabetes. This study aimed to examine the splenoprotective effect of hesperidin and the mechanisms underlying its capacity to reduce oxidative stress and inflammation-mediated spleen damage in diabetes. The diabetic rats used in this study were induced with a 65 mg per kg body weight of streptozotocin. This was followed by 4 weeks of continuous daily dosage of hesperidin treatment at 100 mg/kg body weight. The results showed that hesperidin improved spleen weight and histopathological alterations in the diabetic rats. The hesperidin-treated diabetic group showed a marked induction of SOD and GPx enzymes and moderated malondialdehyde level. This was in addition to an obvious decrease in the levels of TNF-α and NF-á´B in the diabetic rat spleen. Through a remarkable upregulation in Bcl-xL and downregulation in Bax and cleaved caspase-3 proteins, hesperidin supplementation rescued splenic cell apoptosis in the diabetic rats. These findings demonstrate the effectiveness of hesperidin in helping regulate Bcl-2 family proteins and inhibiting the oxidative stress and inflammatory status of hyperglycemia-mediated spleen apoptosis. PRACTICAL APPLICATIONS: Diabetes-related spleen damage increases immune dysfunction, which often results in the heightened risks of infection, morbidity and mortality in diabetic patients. In this work, hesperidin was used in the treatment of rats with diabetes-induced splenic damage. The results were highly encouraging with hesperidin consistently presenting beneficial antioxidant and anti-inflammatory qualities and splenoprotective effect. Research outcomes support the notion that hesperidin treatment could be considered a good strategy for the prevention of diabetic complications in the spleen.