Antidiabetic effect of bitter gourd honey and its mechanism of action assessed using the streptozotocin induced type II diabetic rats

Diabetes is one of the most unmet medical requirements with no permanent treatment and necessitates a comprehensive multi-approach therapy strategy, including natural supplements. The study aims to assess the physicochemical characteristics of bitter gourd honey (BGH) and its impact on metabolic profiles, glucose transporter expression, insulin signalling, antioxidant, anti-apoptotic and anti-inflammatory activities in a streptozotocin-induced diabetic rat model. Standard procedures were used to investigate BGH's physicochemical parameters, in vitro antioxidant activity, and liquid chromatography-mass spectrometry (LC-MS) was used to identify the bioactive components. To test the in vivo effects of BGH, normal and streptozotocin (STZ)-induced diabetic rats were administered orally with BGH (1 and 2 g/kg/day) for 28 days. Body weight, food and water intake, and fasting blood glucose (FBG) levels were assessed weekly. Blood was obtained after the rats were sacrificed. The pancreas, liver, and kidney tested their serum lipid profile, insulin, and anti-oxidative enzyme activity levels (SOD, CAT, and GPx). In addition, the pancreas, liver, kidneys, and skeletal muscle samples were collected and examined histologically and molecularly. In comparison to ascorbic acid, BGH showed substantial antioxidant activity in-vitro. BGH administration to diabetic rats reduced FBG, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), alanine transferase (ALT), aspartate transferase (AST), creatinine, and urea levels significantly (p<0.05) as well as an increase in high-density lipoprotein (HDL), insulin, and anti-oxidative enzyme activity. The pancreatic, liver, and kidney histological abnormalities in diabetic rats treated with BGH were less pronounced. BGH treatment reduced oxidative stress, inflammatory (MYD88, IKKβ, NF-κB, p- NF-κB) and apoptotic indicators in diabetic rats (caspase-3). Furthermore, in BGH-treated diabetic rats, the protein distribution of glucose transporters such as GLUT-2 and GLUT-4 was enhanced in the pancreas, liver, and skeletal muscle. Due to high levels of total phenolic compounds, BGH administration to streptozotocin-induced diabetic rats has protective effects on the pancreas, liver, and kidney as demonstrated by amelioration of oxidative stress, inflammation, and apoptosis-induced damage, while retaining hepatic and renal function and increasing the expression of glucose transporters in diabetic rats. As a result, BGH may be a potential agent to be employed in treating diabetes.