Antidiabetic effects of Psidium x durbanensis Baijnath & Ramcharun ined. (Myrtaceae) leaf extract on streptozotocin-induced diabetes in rats

Ethnopharmacological relevance: Psidium guajava L. leaves are used to treat diabetes in South African folkloric medicine and in other parts of the world. Psidium x durbanensis Baijnath & Ramcharun ined. (PD) is a natural sterile hybrid and congener of Psidium guajava that is expected to share the medicinal properties of the genus Psidium and is widely distributed in South Africa. Aim of the study: This study investigates the antioxidant, antidiabetic effects, and mechanisms of action of hydro-methanolic leaf extracts of PD on streptozotocin-induced diabetes in rats. Material and methods: Phytochemical constituents of hydro-methanolic extract of PD were analyzed by gas chromatography-mass spectrometry (GC-MS). Male Wistar rats 250-300 g body weight (BW) were rendered diabetic after a single intraperitoneal injection with streptozotocin, 45 mg/kg BW. The diabetic rats were treated with hydro-methanolic (20:80 v/v) leaf extracts of PD (400 mg/kg/BW) or subcutaneous injections of regular insulin (2.0U/kg/BW, bid) for 56 days. The body weights of the animals were recorded daily. Fasting blood glucose, glucose tolerance tests, and insulin resistance index were measured. The effects of the extracts on total superoxide dismutase, catalase, and reduced glutathione activities, histopathology, and gene expression of insulin receptor substrate 1 and glucose transporter 4 were determined in the liver, pancreas, and gastrocnemius muscles of the rats. Results: In the acute toxicity studies, there were no signs of toxicity observed for PD up to 2000 mg/kg BW doses. Diabetic animals showed significant weight loss, elevated and reduced fasting blood glucose and insulin, respectively, impaired glucose tolerance and diminished antioxidant enzymes' activities compared to controls. Treatment with PD hydro-methanolic leaf extracts improved body weight, glucose tolerance, insulin resistance, and antioxidant enzymes but not plasma insulin in diabetic animals compared to controls, respectively. GC-MS analysis identified organic acids, alcohols, vitamins, terpenoids, and esters in the extracts. Treatment with PD improved glucose uptake by stimulating mRNA expression of GLUT 4 in gastrocnemius muscles of diabetic animals compared to the untreated control and also restored histological aberrations in the pancreas and liver of diabetic rats compared with the untreated control rats. Conclusion: Collectively, the present study suggests that treatment with PD leaf extracts significantly ameliorated diabetes symptoms and oxidative stress in rats, and these effects may be linked to the bioactive phytoconstituents present in the plant. This study further suggests that PD improves insulin resistance by increasing glucose uptake in gastrocnemius muscles in an insulin-independent manner.