Abstract
Annona reticulata L. (Bullock's heart) is a pantropic tree commonly known as custard apple, which is used therapeutically for a variety of maladies. The present research was carried out to evaluate the possible protective effects of Annona reticulata L. (A. reticulata) ethanolic seed extract on an experimentally induced type 2 diabetes rat model. Male Albino Wistar rats were randomly divided into five groups with six animals in each group viz., control rats in group I, diabetic rats in group II, diabetic rats with 50 and 100 mg/kg/bw of ethanolic seed extract of A. reticulata in groups III and IV, respectively, and diabetic rats with metformin in group V. Treatment was given for 42 consecutive days through oral route by oro-gastric gavage. Administration of A. reticulata seed extract to diabetes rats significantly restored the alterations in the levels of body weight, food and water intake, fasting blood glucose (FBG), insulin levels, insulin sensitivity, HbA1c, HOMA-IR, islet area and insulin positive cells. Furthermore, A. reticulata significantly decreased the levels of triglycerides, cholesterol, LDL, and significantly increased the HDL in diabetic rats. A. reticulata effectively ameliorated the enzymatic (ALT, AST, ALP, GGT) and modification of histopathological changes in diabetic rats. The serum levels of the BUN, creatinine levels, uric acid, urine volume, and urinary protein were significantly declined with a significant elevation in CCr in diabetic rats treated with A. reticulata. MDA and NO levels were significantly reduced with an enhancement in SOD, CAT, and GPx antioxidant enzyme activities in the kidney, liver, and pancreas of diabetic rats treated with A. reticulata. Diabetic rats treated with A. reticulata have shown up-regulation in mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1), Heme oxygenase-1 (HO-1) and protein expression level of Nrf2 with diminution in Keap1 mRNA expression level in pancreas, kidney, and liver. From the outcome of the current results, it can be inferred that seed extract of A. reticulata exhibits a protective effect in diabetic rats through its anti-diabetic, anti-hyperlipidemic, antioxidant and anti-inflammatory effects and could be considered as a promising treatment therapy in the treatment of diabetes mellitus.
Highlights
Diabetes mellitus (DM) is a metabolic disorder characterized by the presence of high levels of glucose in blood that occurs either due to insulin’s deficiency or malfunction [1, 2]
Treatment of diabetic rats with A. reticulata seed extract (50 and 100 mg/kg bw) and metformin caused a significant increase in the body weights when compared to body weights of diabetic rats
The results showed a drastic increase in Homeostatic model assessment (HOMA)-IR in diabetic rats, indicating the insulin resistance, while this was decreased on treatment with 50 or 100 mg/kg A. reticulata seed extract or metformin (Figure 2E)
Summary
Diabetes mellitus (DM) is a metabolic disorder characterized by the presence of high levels of glucose in blood that occurs either due to insulin’s deficiency or malfunction [1, 2]. Hyperglycemia-induced oxidative stress in terms of an increased generation of reactive oxygen/nitrogen species (ROS/RNS) and suppression of antioxidant defenses, such as SOD, CAT, GPx, play vital roles in the pathogenesis of DM [5, 6]. It has been reported that cellular redox homeostasis occurs primarily at the transcriptional level through the regulation of Nrf2/Keap1/ARE pathway [8, 9]. It acts as a critical upstream regulator of global antioxidant response and regulates the genes involved in inflammatory reaction [8, 10]. The study broadened its scope by studying the role of Nrf2/Keap molecular pathway in modifying the effects of A. reticulata
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