Iheagwam Franklyn Nonso, Batiha Gaber El-Saber, Ogunlana Olubanke Olujoke, Chinedu Shalom Nwodo
Department of Biochemistry, Covenant University, P.M.B. 1023 Ota, Ogun State, Nigeria.
Covenant University Public Health and Wellbeing Research Cluster (CUPHWERC), Covenant University, P.M.B. 1023 Ota, Ogun State, Nigeria.
Int J Inflam. 2021 Dec 16;2021:9778486. doi: 10.1155/2021/9778486. eCollection 2021.
This study aims at evaluating the ameliorative role of 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-), 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 . Induction of diabetes significantly ( < 0.05) reduced superoxide dismutase, glutathione-S-transferase, and peroxidase activities. Glutathione and protein stores were significantly ( < 0.05) depleted, while glucose, MDA, interleukin-six (IL-6), and tumour necrosis factor- (TNF-) concentrations were significantly ( < 0.05) increased. A significant ( < 0.05) upregulation of hepatic TNF- and IL-6 expression and downregulation ( < 0.05) of Nrf-2 expression were observed during diabetes onset. TCA treatment significantly ( < 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 ( < 0.05) downregulated hepatic TNF- 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- 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.
本研究旨在评估水叶提取物（TCA）对高脂、低剂量链脲佐菌素诱导的2型糖尿病大鼠模型中高血糖诱导的氧化应激和炎症的改善作用。实验大鼠每天口服400和800mg/kg体重的TCA，持续四周。使用标准方法测定抗氧化酶活性、血浆葡萄糖浓度、蛋白质浓度、氧化应激和炎症生物标志物。还评估了肿瘤坏死因子-α（TNF-）、白细胞介素-6（IL-6）和核因子-红细胞2相关因子2（Nrf-2）的肝脏相对表达。评估了主要TCA植物成分与T2DM诱导的氧化应激相关的生物活性的分子对接和预测。糖尿病诱导显著（<0.05）降低了超氧化物歧化酶、谷胱甘肽-S-转移酶和过氧化物酶活性。谷胱甘肽和蛋白质储备显著（<0.05）耗尽，而葡萄糖、丙二醛、白细胞介素-6（IL-6）和肿瘤坏死因子-（TNF-）浓度显著（<0.05）升高。在糖尿病发病期间观察到肝脏TNF-和IL-6表达显著（<0.05）上调，Nrf-2表达下调（<0.05）。TCA治疗显著（<0.05）调节了全身糖尿病诱导的氧化应激和炎症、mRNA表达失调以及大分子代谢失调。然而，只有800mg/kg TCA治疗显著（<0.05）下调了肝脏TNF-表达。9-氧杂双环[3.3.1]壬烷-2,6-二醇和1,2,3-苯三酚在Nrf-2、IL-6和TNF-结合口袋中与格列本脲的结合相当。它们被预测为GST A和M底物、JAK2表达、核糖磷酸3-表异构酶、NADPH过氧化物酶和葡萄糖氧化酶抑制剂。这些结果表明，TCA通过激活Nrf-2基因改善高血糖诱导的氧化应激和炎症。
