Alshahrani Saeed, Anwer Tarique, Alam Mohammad Firoz, Ahmed Rayan A, Khan Gyas, Sivakumar Sivagurunathan Moni, Shoaib Ambreen, Alam Prawez, Azam Faizul
Pharmacology & Toxicology Department, Pharmacy College, Jazan University, Gizan, Saudi Arabia.
Pharmaceutics Department, Pharmacy College, Jazan University, Gizan, Saudi Arabia.
J Food Biochem. 2021 Jun 21:e13807. doi: 10.1111/jfbc.13807.
The aim was to investigate whether thymoquinone (TQ) attenuates hyperglycemia-induced insulin resistance in experimental type 2 diabetes. Type 2 diabetes mellitus (T2DM) was induced by injection of streptozotocin (STZ, 40 mg/kg) in high fat diet (HFD) rats. The levels of glucose, insulin, area under curve (AUC) of glucose, lipid profile parameters, homeostasis model assessment of insulin resistance (HOMA-IR), peroxisome proliferator-activated receptor-γ (PPARγ), and dipeptidyl peptidase peptidase-IV (DPP-IV) were evaluated in HFD + STZ-induced type 2 diabetic rats. TQ treatment significantly reduced elevated levels of glucose, AUC of glucose, insulin, and DPP-IV in diabetic-treated groups. In addition, TQ treatment significantly reduced high levels of triglycerides (TG) and cholesterols (total, low-density and very low-density lipoprotein) accompanied by significant augmentation in high-density lipoprotein (HDL) levels in diabetic-treated groups. However, TQ treatment significantly improved insulin sensitivity in diabetic-treated groups, which was confirmed by increased level of PPARγ and decreased level of HOMA-IR. Molecular docking of TQ exhibited substantial binding affinity with PPARγ and DPP-IV target proteins, which is supported by in vivo results. These results demonstrate that TQ attenuates hyperglycemia-induced insulin resistance by counteracting hyperinsulinemia, improving lipid profile, insulin sensitivity, and inhibiting DPP-IV. PRACTICAL APPLICATIONS: T2DM results in relentless hyperglycemia which eventually progress to a state of insulin resistance. TQ is an active principle compound found in Nigella sative seed, having myriad of traditional medicinal values. Administration of TQ significantly prevented hyperglycemia, hyperinsulinemia, hyperlipidemia, insulin resistance, and inhibited DPP-IV in experimental type 2 diabetes. The in vivo results are also supported by molecular docking study of PPARγ and DPP-IV target proteins. Thus, we hypothesize that TQ can be used as an alternative natural drug in the management of hyperglycemia-induced insulin resistance in T2DM.
本研究旨在探讨百里醌（TQ）是否能减轻实验性2型糖尿病中高血糖诱导的胰岛素抵抗。通过给高脂饮食（HFD）大鼠注射链脲佐菌素（STZ，40mg/kg）诱导2型糖尿病（T2DM）。评估了HFD+STZ诱导的2型糖尿病大鼠的血糖、胰岛素水平、葡萄糖曲线下面积（AUC）、血脂参数、胰岛素抵抗稳态模型评估（HOMA-IR）、过氧化物酶体增殖物激活受体γ（PPARγ）和二肽基肽酶IV（DPP-IV）水平。TQ治疗显著降低了糖尿病治疗组中升高的血糖、葡萄糖AUC、胰岛素和DPP-IV水平。此外，TQ治疗显著降低了糖尿病治疗组中高水平的甘油三酯（TG）和胆固醇（总胆固醇、低密度脂蛋白和极低密度脂蛋白），同时高密度脂蛋白（HDL）水平显著升高。然而，TQ治疗显著改善了糖尿病治疗组的胰岛素敏感性，这通过PPARγ水平升高和HOMA-IR水平降低得到证实。TQ的分子对接显示与PPARγ和DPP-IV靶蛋白具有显著的结合亲和力，体内结果也支持这一点。这些结果表明，TQ通过对抗高胰岛素血症、改善血脂谱、胰岛素敏感性和抑制DPP-IV来减轻高血糖诱导的胰岛素抵抗。实际应用：T2DM导致持续的高血糖，最终发展为胰岛素抵抗状态。TQ是黑种草籽中的一种活性成分，具有多种传统药用价值。在实验性2型糖尿病中，TQ给药显著预防了高血糖、高胰岛素血症、高脂血症、胰岛素抵抗，并抑制了DPP-IV。PPARγ和DPP-IV靶蛋白的分子对接研究也支持体内结果。因此，我们假设TQ可作为一种替代天然药物用于治疗T2DM中高血糖诱导的胰岛素抵抗。
