Bradykinin Potentiating Factor from Egyptian Honey Bee Venom Fraction: A Potential Therapeutic Agent for Type 1 Diabetes
Authors: Habib Tito N , Raheem Soheir A El , El-Sabry Abu-Amra , AboElkhair Hossam A. 
Published: August 2023

Background: Natural products have been a valuable source of potential drug leads. In recent years, there has been growing interest in exploring the therapeutic potential of natural products in the management of diabetes and related complications. Honey bee venom (HBV) is one such natural product that has been known to exhibit various biological activities, including antihypertensive, analgesic, anti-inflammatory, and antioxidant effects. Bradykinin potentiating factor (BPF) is a fraction of HBV that has been shown to have potential therapeutic effects. Therefore, this study aimed to investigate the potential antidiabetic effect of BPF in streptozotocin (STZ)-induced diabetic rats.
Materials and Methods: An in vivo study was conducted on fifty albino male rats, which were divided into five groups: (GI) vehicle control animals, (GII) diabetic STZ-induced group, (GIII) nondiabetic BPF-treated group, (GIV) BPF-injected animals post-treated with STZ, and (GV) STZ-injected animals post-treated with BPF. The rats were fasted overnight before the experiment, and then their blood glucose levels were measured using a glucometer. The rats were then administered STZ to induce diabetes, except for the nondiabetic control group. The rats were treated with BPF at a dose of 0.1 mg/kg body weight for 15 days. After 15 days, the rats were euthanized, and their plasma glucose levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (C-RP) were evaluated and compared to STZ-treated diabetic rats and vehicle control rats. The histological and immunohistochemical analyses were carried out to predict the potential role of BPF to regulate metabolic and inflammatory variables associated with DM1. The mRNA expression of apelin and resistin genes was quantified using qRT-PCR, and the plasma protein profiles of C-RP and apelin were examined using sodium dodecyl sulphate-Polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting techniques.
Results: The data showed that STZ-induced DM1rats (GII) rats had significantly higher levels of plasma glucose, ALT, and AST than BPF-treated (GIII, GIV, GV) and nondiabetic control (GI) rats. The BPF-treated rats had significantly lower levels of plasma glucose, ALT, and AST than the STZ-treated rats. RT-qPCR revealed that the concentrations of apelin and resistin genes were significantly lower in BPF-treated (GIII, GIV, GV) and vehicle control (GI) groups than in STZ-treated (GII) rats. The concentrations of C-RP (28.3 kDa) and apelin (16 kDa) proteins were higher in STZ-treated (GII) rats than in BPF-STZ treated (GIV), STZ-BPF treated (GV), and negative control (GI) rats. BPF exhibited a significant reduction in the severity of these histological changes compared to the STZ-induced diabetic group (GII). The increase in GLUT4 expression by BPFtreatment may facilitate glucose uptake and utilization in liver tissue, leading to better glycemic control in diabetic rats.
Conclusion: This study provides evidence for the therapeutic and protective effects of BPF against STZ-induced type 1 diabetes (DM1) complications in rats. The results indicated that BPFhas antihyperglycemic and antioxidant effects, as demonstrated by improved biochemical parameters. BPF treatment was found to modulate the expression of apelin, resistin, C-RP proteins in the blood plasma, and GULT4 in the liver tissue of STZ-induced diabetic rats. The mechanisms underlying how BPF exerts its antihyperglycemic and antioxidant effects in DM1 were further examined. While BPF has been shown to have potential therapeutic effects for diabetes in preclinical studies, it is unlikely to be used as a standalone treatment. Instead, it should be used in combination with other treatments as part of a comprehensive diabetes management plan.