Almasoudi Hassan H, Nahari Mohammed H, Binshaya Abdulkarim S, Hakami Mohammed Ageeli, Alhazmi Abdulfattah Y, Al Shmrany Humood, Alqasem Abdullah, Khan Farhan R
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia.
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia.
J Biomol Struct Dyn. 2024 Mar 9:1-18. doi: 10.1080/07391102.2024.2325659.
Diabetes affects people of all ages, regardless of gender and background. To date, there is no evidence for the effect of sakuranetin against the streptozotocin (STZ)-induced diabetes paradigm. The research was directed to evaluate the antidiabetic activity of sakuranetin in the STZ model invoking the diabetes-induced disease paradigm. STZ (I.P. 60 mg/kg) is directed to induce type 2 diabetes in experimental rats. Recent research pursued to regulate the anti-diabetic ability of sakuranetin at both 10 and 20 mg/kg in STZ-induced rats. Furthermore, molecular docking research was implemented to evaluate sakuranetin requisite attraction to inflammatory indicators. Various anti-diabetic [(glucose, hemoglobin A1c (HbA1c), and insulin)], lipid profile [triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL)], hematological parameters [Hemoglobin (HGB), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), platelet (PLT), and white blood cells (WBC), pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], antioxidant level [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH)], lipid oxidation, and caspase-3 were evaluated. Furthermore, molecular docking and dynamics were performed for TNF-α (2AZ5), IL-6 (1ALU), IL-1β (6Y8M), Caspase-3 (1NME) and serum insulin (4IBM) target ligands. Sakuranetin treatment at both doses restored the biochemical parameters i.e. blood glucose, insulin, HbA1c, lipid profile, hematological parameters, pro-inflammatory markers, antioxidant levels, lipid oxidation, and caspase-3 in the context of diabetic rats. It also showed favorable binding affinity on inflammatory markers. Sakuranetin binds to proteins 2AZ5, 1ALU, 6Y8M, 1NME, and 4IBM at -7.489, -6.381, -6.742, -7.202, and -8.166 Kcal/mol, respectively. All of the findings from the molecular dynamics simulations points toward a considerable change in the conformational dynamics of protein upon binding with sakuranetin. The potential use of sakuranetin as an alternative diabetes medication will aid future research as a potent anti-diabetic agent.
糖尿病影响所有年龄段的人，无论性别和背景如何。迄今为止，没有证据表明樱花素对链脲佐菌素（STZ）诱导的糖尿病模型有影响。该研究旨在评估樱花素在STZ诱导的糖尿病疾病模型中的抗糖尿病活性。STZ（腹腔注射60mg/kg）用于诱导实验大鼠患2型糖尿病。最近的研究致力于在STZ诱导的大鼠中，评估10mg/kg和20mg/kg剂量的樱花素的抗糖尿病能力。此外，进行了分子对接研究，以评估樱花素对炎症指标的必要吸引力。评估了各种抗糖尿病指标[血糖、糖化血红蛋白（HbA1c）和胰岛素]、血脂指标[甘油三酯（TG）、总胆固醇（TC）和高密度脂蛋白（HDL）]、血液学参数[血红蛋白（HGB）、红细胞压积（PCV）、红细胞（RBC）、平均红细胞体积（MCV）、血小板（PLT）和白细胞（WBC）]、促炎细胞因子[肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）]、抗氧化水平[过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）]、脂质氧化和半胱天冬酶-3。此外，对TNF-α（2AZ5）、IL-6（1ALU）、IL-1β（6Y8M）、半胱天冬酶-3（1NME）和血清胰岛素（4IBM）靶配体进行了分子对接和动力学研究。在糖尿病大鼠中，两种剂量的樱花素治疗均恢复了生化参数，即血糖、胰岛素、HbA1c、血脂指标、血液学参数、促炎标志物、抗氧化水平、脂质氧化和半胱天冬酶-3。它还对炎症标志物表现出良好的结合亲和力。樱花素分别以-7.489、-6.381、-6.742、-7.202和-8.166kcal/mol的亲和力与蛋白质2AZ5、1ALU、6Y8M、1NME和4IBM结合。分子动力学模拟的所有结果都表明，蛋白质与樱花素结合后，其构象动力学发生了显著变化。樱花素作为一种替代糖尿病药物的潜在用途，将有助于未来作为一种有效的抗糖尿病药物的研究。
