Abstract
This study aims at evaluating the ameliorative role of Terminalia catappa aqueous leaf extract (TCA) on hyperglycaemia-induced oxidative stress and inflammation in a high-fat, low dose streptozotocin-induced type 2 diabetic rat model. Experimental rats were treated orally with 400 and 800 mg/kg bw TCA daily for four weeks. Antioxidant enzyme activities, plasma glucose concentration, protein concentration, oxidative stress, and inflammation biomarkers were assayed using standard methods. Hepatic relative expressions of tumour necrosis factor-alpha (TNF-α), interleukin-six (IL-6), and nuclear factor-erythroid 2 related factor 2 (Nrf-2) were also assessed. Molecular docking and prediction of major TCA phytoconstituents' biological activity related to T2DM-induced oxidative stress were evaluated in silico. Induction of diabetes significantly (p < 0.05) reduced superoxide dismutase, glutathione-S-transferase, and peroxidase activities. Glutathione and protein stores were significantly (p < 0.05) depleted, while glucose, MDA, interleukin-six (IL-6), and tumour necrosis factor-α (TNF-α) concentrations were significantly (p < 0.05) increased. A significant (p < 0.05) upregulation of hepatic TNF-α and IL-6 expression and downregulation (p < 0.05) of Nrf-2 expression were observed during diabetes onset. TCA treatment significantly (p < 0.05) modulated systemic diabetic-induced oxidative stress and inflammation, mRNA expression dysregulation, and dysregulated macromolecule metabolism. However, only 800 mg/kg TCA treatment significantly (p < 0.05) downregulated hepatic TNF-α expression. 9-Oxabicyclo[3.3.1]nonane-2,6-diol and 1,2,3-Benzenetriol bound comparably to glibenclamide in Nrf-2, IL-6, and TNF-α binding pockets. They were predicted to be GST A and M substrate, JAK2 expression, ribulose-phosphate 3-epimerase, NADPH peroxidase, and glucose oxidase inhibitors. These results suggest that TCA ameliorates hyperglycaemia-induced oxidative stress and inflammation by activating Nrf-2 gene.
Highlights
Diabetes mellitus (DM) is a metabolic and endocrine disease of chronic nature which arises from a lack of insulin secretion, action, or both
According to the International Diabetes Foundation (IDF), as of 2019, over 450 million adults were living with diabetes worldwide. is number is expected to increase by 2045 to about 700 million, with most of the diabetes risk and burden being type 2 diabetes mellitus (T2DM) [3]. ere is a paradigm shift in Africa, in which the major focus of the continent’s health system has moved from infectious diseases to noncommunicable diseases. is recent trend is due to increased urbanisation and lifestyle changes [4,5,6]
Despite the reports on the antioxidant property of T. catappa in diabetic and nondiabetic animal models [32,33,34,35], information on the molecular mode of antioxidant and anti-inflammatory activity of T. catappa in T2DM animal model is lacking. is study evaluates the role of Terminalia catappa aqueous leaf extract in ameliorating hyperglycaemia-induced oxidative stress and inflammation in high-fat diet (HFD)/low-dose streptozotocin-induced diabetic rats. e extract’s role on the expression of some genes relevant to redox status and inflammation was evaluated
Summary
Diabetes mellitus (DM) is a metabolic and endocrine disease of chronic nature which arises from a lack of insulin secretion, action, or both. Oxidative stress arises whenever the cellular redox balance is disrupted, leading to loss of biomolecular integrity and membrane damage It promotes diabetes onset and aggravates this disorder and its associated complications by disrupting insulin release and action [13,14,15]. Numerous pieces of information show that hyperglycaemia-induced oxidative stress is a major player in the pathogenesis and progression of T2DM and its related complications; tackling it cannot be overemphasised [11, 17, 22,23,24,25]. Despite the reports on the antioxidant property of T. catappa in diabetic and nondiabetic animal models [32,33,34,35], information on the molecular mode of antioxidant and anti-inflammatory activity of T. catappa in T2DM animal model is lacking. is study evaluates the role of Terminalia catappa aqueous leaf extract in ameliorating hyperglycaemia-induced oxidative stress and inflammation in high-fat diet (HFD)/low-dose streptozotocin-induced diabetic rats. e extract’s role on the expression of some genes relevant to redox status and inflammation was evaluated
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