Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 Gene
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 T...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | International Journal of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/9778486 |
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| author | Franklyn Nonso Iheagwam Gaber El-Saber Batiha Olubanke Olujoke Ogunlana Shalom Nwodo Chinedu |
| author_facet | Franklyn Nonso Iheagwam Gaber El-Saber Batiha Olubanke Olujoke Ogunlana Shalom Nwodo Chinedu |
| author_sort | Franklyn Nonso Iheagwam |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c8f355451425488a92bafb7016ec12cb |
| institution | Kabale University |
| issn | 2042-0099 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Inflammation |
| spelling | doaj-art-c8f355451425488a92bafb7016ec12cb2025-02-03T01:31:49ZengWileyInternational Journal of Inflammation2042-00992021-01-01202110.1155/2021/9778486Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 GeneFranklyn Nonso Iheagwam0Gaber El-Saber Batiha1Olubanke Olujoke Ogunlana2Shalom Nwodo Chinedu3Department of BiochemistryDepartment of Pharmacology and TherapeuticsDepartment of BiochemistryDepartment of BiochemistryThis 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.http://dx.doi.org/10.1155/2021/9778486 |
| spellingShingle | Franklyn Nonso Iheagwam Gaber El-Saber Batiha Olubanke Olujoke Ogunlana Shalom Nwodo Chinedu Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 Gene International Journal of Inflammation |
| title | Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 Gene |
| title_full | Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 Gene |
| title_fullStr | Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 Gene |
| title_full_unstemmed | Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 Gene |
| title_short | Terminalia catappa Extract Palliates Redox Imbalance and Inflammation in Diabetic Rats by Upregulating Nrf-2 Gene |
| title_sort | terminalia catappa extract palliates redox imbalance and inflammation in diabetic rats by upregulating nrf 2 gene |
| url | http://dx.doi.org/10.1155/2021/9778486 |
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