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. 2021 Dec 16:2021:9778486.
doi: 10.1155/2021/9778486. eCollection 2021.

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

Franklyn Nonso Iheagwam  1   2 , Gaber El-Saber Batiha  3 , Olubanke Olujoke Ogunlana  1   2 , Shalom Nwodo Chinedu  1   2
Affiliations

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

Franklyn Nonso Iheagwam et al. Int J Inflam. .

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.

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Conflict of interest statement

The authors declare that they have no actual or potential competing financial interest.

Figures

Figure 1
Figure 1
Effect of T. catappa aqueous extract treatment on bodyweight changes in HFD/STZ-induced diabetic rats. Bars represent proportion. Bars with different superscripts are significantly different at p < 0.05.
Figure 2
Figure 2
Effect of T. catappa aqueous extract treatment on fasting blood glucose in HFD/STZ-induced diabetic rats after 14 and 28 days of treatment. Bars represent mean ± SEM (n = 6). Bars with different superscripts are significantly different, while those with the same superscripts are not significantly different at p < 0.05.
Figure 3
Figure 3
Effect of T. catappa aqueous extract treatment on (a) plasma, (b) hepatic, (c) renal, and (d) erythrocyte superoxide dismutase (SOD) activity in HFD/STZ-induced diabetic rats. Bars represent mean ± SEM (n = 6). Bars with different superscripts are significantly different, while those without superscripts are not significantly different at p < 0.05.
Figure 4
Figure 4
Effect of T. catappa aqueous extract treatment on (a) plasma, (b) hepatic, (c) renal, and (d) erythrocyte peroxidase (Px) activity in HFD/STZ-induced diabetic rats. Bars represent mean ± SEM (n = 6). Bars with different superscripts are significantly different, while those without superscripts are not significantly different at p < 0.05.
Figure 5
Figure 5
Effect of T. catappa aqueous extract treatment on (a) plasma, (b) hepatic, (c) renal, and (d) erythrocyte glutathione-S-transferase (GST) activity in HFD/STZ-induced diabetic rats. Bars represent mean ± SEM (n = 6). Bars with different superscripts are significantly different, while those without superscripts are not significantly different at p < 0.05.
Figure 6
Figure 6
Effect of T. catappa aqueous extract treatment on (a) plasma, (b) hepatic, (c) renal, and (d) erythrocyte reduced glutathione (GSH) concentration in HFD/STZ-induced diabetic rats. Bars represent mean ± SEM (n = 6). Bars with different superscripts are significantly different at p < 0.05.
Figure 7
Figure 7
Effect of T. catappa aqueous extract treatment on (a) plasma, (b) hepatic, (c) renal, and (d) erythrocyte lipid peroxidation (MDA) concentrations in HFD/STZ-induced diabetic rats. Bars represent mean ± SEM (n = 6). Bars with different superscripts are significantly different at p < 0.05.
Figure 8
Figure 8
Effect of TCA on (a) Nrf-2, (b) IL-6, and (c) TNF-α mRNA expression in the liver of HFD/STZ-induced diabetic rats. Bars represent mean ± SEM (n = 3). Bars with different superscripts are significantly different at p < 0.05.
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