Evaluation of antioxidant potential, anti-inflammatory effect and the mechanisms of action of phenolic compounds from South African indigenous plants used in the management of diabetes-related male infertility

Abstract

Diabetes mellitus (DM) is a chronic metabolic disease characterised by hyperglycaemia. The rise in mortality associated with DM is attributed to the complications driven by prolonged hyperglycaemia which leads to excessive production of free radicals. The imbalance in the level of free radicals causes oxidative stress and inflammation. Hyperglycaemic-induced oxidative stress and inflammation have previously been shown to cause damage and a significant impact on male sub-/infertility by reducing sperm parameters such as sperm motility, sperm DNA and mitochondrial membrane integrity, and sperm capacitation. Over the years, these diabetic complications have been treated with conventional drugs, however, the adverse effects associated with their long usage have necessitated searching for safe and effective treatment that targets the pathological pathways leading to diabetic-related male infertility. Therefore, the present study identified potential medicinal plants (Androstachys johnsonii and Garcinia livingstonei) used in traditional medicine for the treatment of DM-related male infertility and investigated their effects in the amelioration of reproductive dysfunction linked to hyperglycaemia. The study is premised on the hypothesis that phenolic-rich South African medicinal plants could exhibit some antidiabetic effects, and attenuate oxidative stress and inflammation in the semen of diabetic individuals with male infertility. The medicinal plants were identified in the first phase of the study, and the plant extracts were prepared. Preliminary studies were conducted to determine the hypoglycaemic, anti-inflammatory, and antioxidant properties of the plant extract. The plant extracts were tested on sperm cells induced with hyperglycaemia in vitro. Normal sperm cells were collected from 25 male individuals. Each sample was divided into a normal group sample, hyperglycaeimia-induced sample, and a sample induced with hyperglycaemia and treated with the plant extract. Phenolic compounds that could be responsible for the biological activities were identified from the plant extracts and among which, flavonoids were majorly abundant in both plant extracts. The results demonstrated high antioxidant capacity in both plant extracts through the determination of ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and 2,2-diphenyl-1-pycrylhydrazyl (DPPH). Also, the extracts exhibited significant (P<0.05) α- glucosidase inhibitory activity higher than acarbose. Both extracts displayed anti-inflammatory effects significantly (P<0.05), depending on the concentration of the plant extract. While no cell toxicity on C3A hepatocarcinoma cells was observed with all test concentrations of G. livingstonei, the highest concentration (250 μg/mL) of the A. johnsonii extract showed cell toxicity. Hyperglycaemia induction led to a significant (P<0.05) increase in the production of ROS, which was significantly reduced after exposure to both plant extracts. Both catalase and superoxide dismutase (SOD) activities remained unchanged after hyperglycaemia induction and treatment with both plant extracts. Induction of hyperglycaemia led to the decline of sperm parameters: motility, vitality, DNA integrity, mitochondrial membrane potential, capacitation, and acrosome reaction. Treatment with G. livingstonei led to increasing in all tested sperm parameters, with the lowest concentration exhibiting maximum protective effects. The administration of the A. johnsonii extract on hyperglycaemic cells also led to an increase in all, with the highest concentration (1 μg/mL) leading to the highest protective effects. The findings of this study show that both medicinal plants have potential therapeutic effects to ameliorate oxidative stress-causing hyperglycemia in human semen. The results of this study revealed that both A. johnsonii and G. livingstonei can potentially reduce glucose levels, and exhibit protective effects on the sperm cells of males with DM. However, further studies in vitro and in vivo are necessary to understand the safe and effective optimum concentrations, and other mechanisms of action through which the plant extracts exhibit their effects in the treatment of diabetic complications.