WITHDRAWN: In vivo Investigation of The Antidiabetic potential of Manilkara hexandra leaves and fruits extracts against streptozotocin-induced hyperglycaemia in rats

Abstract

<title>Abstract</title> Diabetes mellitus has been one of the most crippling diseases with huge social, health, and economic consequences. <italic>Manilkara hexandra</italic> (Roxb.) Dubard is a small to medium sized evergreen edible fruit-producing tree belonging to the family Sapotaceae and cultivated in Egypt. The main goal of the current study is to evaluate the effect of oral administration of <italic>M. hexandra</italic> different extracts including fruit methanolic soluble portion, leaf methanolic soluble portion, fruit aqueous methanolic extract, and leaf aqueous methanolic extract for 30 days at a dose of 1/10 of their LD ₅₀ (2 g/kg b.w) on streptozotocin-induced diabetic rats. Glucose and insulin were assayed in blood while reduced glutathione (GSH), nitric oxide (NO), lipid peroxidation (TBARS), and thioredoxin reductase (TrxR) activity were measured in pancreatic tissues. Phytochemical investigation of <italic>M. hexandra</italic> leaf and fruit revealed the purification of five compounds among which three compounds were isolated from the leaf and identified as <italic>β</italic> -sitosterol, <italic>β</italic> -amyrin, and 3- <italic>O</italic> - <italic>β</italic> -D-glucopyranosy-protobassic acid, respectively. Moreover, two flavonoids were identified in <italic>M. hexandra</italic> fruit <italic>viz</italic> . quercetin 3- <italic>O</italic> -α-L-rhamnopyranoside and myricetin 3-O-α-L-rhamnopyranoside. The results obtained from this study revealed that streptozotocin administration resulted in significant elevation in the level of both lipid peroxidation and nitric oxide with depletion in the level of reduced glutathione as compared with control accompanied with hyperglycemia, hypo-insulinemia and low insulin sensitivity. Moreover, the activity of pancreatic TrxR was lower than the control group. Oral administration of the diabetic rats with the extracts normalizes the previous biochemical parameters reaching near the normal level. <italic>M. hexandra</italic> fruit and leaf aqueous methanolic extract and methanolic soluble portion exhibited significant antidiabetic activity and corrected the insulin level and sensitivity in experimentally induced diabetic rats.