Synergistic properties of garlic and Citrullus colocynthis on reproductive injury caused by diabetes in male rats: Structural and molecular evidence

This study evaluates the synergistic effect of garlic and Citrullus colocynthis on diabetic reproductive damage by suppressing the AGEs/RAGE/Nox-4 signaling pathway. Thirty-five male Wistar rats were divided into five groups (n = 7/group): Control, Diabetic, Diabetic+G (Garlic, 1 mL/100 g b.w), Diabetic+C (C. colocynthis, 10 mg/kg b.w) and Diabetic+GC (Garlic, 1 mL/100 g b.w and C. colocynthis, 10 mg/kg b.w) groups. At the end of the experimental period (30 days), in diabetic rats, glucose increased, and body & testis weight, luteinizing hormone (LH) and testosterone levels, and sperm count decreased significantly and histopathological injuries were observed. In addition, they have increased testicular apoptosis and oxidative stress. Also, the mechanism based on advanced glycation end products (AGEs)/receptors for advanced glycation end products (RAGE)/NADPH oxidase-4 (Nox-4) was activated in diabetic rats. Separate consumption of garlic and C. colocynthis in Diabetic+G and Diabetic+C groups alleviated the negative adverse effect of diabetes to some extent, but when they were used in the combination form (Diabetic+GC) improvement was profound. Testis histopathology, increased body and testis weight, and enhanced capacity in protecting diabetic reproductive injury was seen. Decreases in testosterone and LH concentration and sperm count in diabetic rats were also reversed by combined administration of garlic and C. colocynthis. It regulated oxidative stress markers, meanwhile reducing caspase-3 immunoexpression. In addition, overexpression of RAGE, Nox-4 and nuclear transcription factor-kappa B (NF-kappa B) was inhibited by the combination of garlic and C. colocynthis. Practical Applications Diabetes mellitus is wide spread all around the world with variety of complications in body including reproductive system in which patients suffer from physical and psychological aspects. Despite many efforts in providing agents for controlling diabetes and its complications, economic conditions of some countries make it difficult for people to provide costly medicine and as a result, they have to bear the complications until they pass away. However, traditional medicine is still finding its way, especially in poor countries with emphasis on medicinal plants. There have been many studies on plants to alleviate diabetes or its side effects. But, using one plant for long term, may be not so effective. Here, we attempted to find whether two plants from two different species can show more efficacy than each one alone. We noticed garlic and Citrullus colocynthis despite having beneficial effects when used alone, they could show synergistic effects in combination.