Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 Gene

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.

α-Lipoic Acid Protects against Cyclosporine A-Induced Hepatic Toxicity in Rats: Effect on Oxidative Stress, Inflammation, and Apoptosis

“…WF10308001). Reaction mixtures were incubated for 10 min at 95 • C, followed by 40 cycles of 15 s at 95 • C, and 30 s at 60 • C. The primer sequences used were rat SOD1: forward, 5 -TTTTGCTCTCCCAGGTTCCG-3 ; reverse, 5 -CCCATGCTCGCCTTCAGTTA-3 [20], rat caspase-3: forward, 5 -GTGGAACTGACGATGATATGGC-3 ; reverse, 5 -CGCAAAGTGACTGGATGA ACC-3 [21], rat Nrf-2: forward, 5 -GGGCAAAAGCTCTCCATATTCC-3 ; reverse 5 -GAGCGGC AACTTTATTCTTCCC-3 ) [22], rat TNF-α: forward, 5 -CTGGCGTGTTCATCCGTTC-3 ; reverse, 5 -GGCTCTGAGGAGTAGACGATAA-3 [23], rat NF-κB: forward, 5 -AGAGCAACCGAAACA GAGAGG-3 ; reverse, 5 -TTTGCAGGCCCCACATAGTT-3 [24]. The primers sequences for rat βactin were 5 -AAGATCCTGACCGAGCGTGG-3 (Forward); and 5 -CAGCACTGTGTTGGCAT AGAGG-3 (Reverse) [21].…”

Terminalia catappa reverses insulin resistance, improves glucose transport and activates PI3K/AKT signalling in high fat/ streptozotocin-induced diabetic rats

“…Plant specimen collection, identi cation and preparation T. catappa (TC) mature leaves were plucked from Covenant University, Ota, Nigeria. They were authenticated by Dr. J. O. Popoola and deposited at the Forestry Research Institute of Nigeria (FRIN) (FHI 112775), dried, processed and crude aqueous extract (TCA) prepared using a rotary evaporator as described by Iheagwam, et al 23 and Iheagwam, et al 21 . Studies complied with local and national ethical guidelines/regulations on the usage of plants.…”

“…The method previously described by Iheagwam, et al 21 was used to induce T2DM using a combination of a high-fat diet (HFD) and low dose STZ (30 mg/kg bw). Experimental animals (n = 30) were randomly placed in ve (5) groups containing 6 rats each, as earlier reported in a previous study by Iheagwam, et al 21 as depicted in Fig. 1.…”

“…Trizol® reagent (TransGen Biotech Co., China) was used to extract total RNA from the hepatic tissues and reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyse the expression of insulin receptor substrate 1 (IRS-1), glucose transporter isoform 4 (GLUT-4), DPP-IV, glucagon-like peptide-1 (GLP-1), protein kinase B (AKT) and phosphatidylinositol 3-kinase (PI3K) following set parameters and genespeci c primers in Table 1 for rst-strand cDNA synthesis, with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as reference gene 21 . PCR products were run on ethidium bromide-stained agarose gel (1.5%) (Sigma Aldrich, Germany) in triplicates and viewed under UVP BioDoc-It™ Imaging system (Upland, CA, USA).…”

“…Terminalia cattapa, also known as tropical almond, is a well known medicinal plant in Nigeria with antimicrobial 16 , antibacterial 17 , anti-in ammatory, anti-HIV 18 , hypoglycaemic 19 , analgesic, wound healing, antioxidant, radical scavenging, hepatoprotective, anticancer, antimutagenic and antiaging properties 20 . Iheagwam, et al 21 reported that the aqueous leaf extract of T. cattapa could palliate redox imbalance and in ammation in high fat/low dose streptozotocin-induced diabetic rats. Previous reports have shown elevated oxidative stress and increased free radical generation truncate IST normal processes, leading to unfavourable downstream effects 11,22 .…”