关键词: Molecular docking Oxidative stress Pro-inflammatory cytokines Streptozotocin Thymoquinone

Mesh : Animals Benzoquinones / pharmacology Molecular Docking Simulation Diabetes Mellitus, Experimental / metabolism drug therapy Rats Apoptosis / drug effects Oxidative Stress / drug effects Male Nitrosative Stress / drug effects Liver / metabolism drug effects pathology Inflammation / metabolism drug therapy Antioxidants / pharmacology metabolism Blood Glucose / metabolism Rats, Wistar Streptozocin

来  源:   DOI:10.1038/s41598-024-62780-y   PDF(Pubmed)

Abstract:
Diabetes mellitus (DM) is a complex metabolic condition that causes organ dysfunction. The current experiment sought to determine the effect of thymoquinone (TQ) on hyperglycemia, hyperlipidemia, oxidative/nitrosative stress, inflammation, and apoptosis in diabetic rats prompted by streptozotocin (STZ) (55 mg/kg body weight i/p). The animals were allocated into control, TQ (50 mg/kg B.W. orally administered for 4 succeeding weeks), Diabetic, and Diabetic + TQ groups. This study confirmed that TQ preserves the levels of insulin, fasting blood glucose, HOMA β-cell indices, HbA1c %, body weight, and lipid profile substantially relative to the DC group. Furthermore, hepatic antioxidant (CAT, GSH, and T-SOD) values were reduced. Conversely, the enzymatic activity of liver functions (AST, ALT, ALP, cytochrome P450, and hepatic glucose-6-phosphatase), lipid peroxidation (MDA), pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), nitric oxide (NO) and inflammatory marker (CRP) enhanced with STZ administration, which is substantially restored after TQ treatment. Relative to the diabetic rats, TQ reestablished the hepatic architectural changes and collagen fibers. Additionally, TQ downregulated the intensity of the immunohistochemical staining of pro-apoptotic marker (caspase-3), p53, and tumor necrosis factor-alpha (TNF-α) proteins in hepatic tissues. Furthermore, TQ displayed abilities to interact and inhibit the binding site of caspase-3, interleukin-6 receptor, interleukin-1 receptor type 1, TNF receptor superfamily member 1A, and TNF receptor superfamily member 1B in rats following the molecular docking modeling. All these data re-establish the liver functions, antioxidant enzymes, anti-inflammatory markers, and anti-apoptotic proteins impacts of TQ in STZ-induced DM rats. Founded on these outcomes, the experiment proposes that TQ is a novel natural supplement with various clinical applications, including managing DM, which in turn is recommended to play a pivotal role in preventing the progression of diabetes mellitus.
摘要:
糖尿病(DM)是一种复杂的代谢疾病,可导致器官功能障碍。当前的实验试图确定百里香醌(TQ)对高血糖的影响,高脂血症,氧化/亚硝基应激,炎症,链脲佐菌素(STZ)(55mg/kg体重i/p)促进糖尿病大鼠凋亡。这些动物被分配到对照组,TQ(连续4周口服50mg/kgB.W.),糖尿病,和糖尿病+TQ组。这项研究证实,TQ保留了胰岛素的水平,空腹血糖,HOMAβ细胞指数,HbA1c%,体重,和脂质分布基本上相对于DC基团。此外,肝脏抗氧化剂(CAT,GSH,和T-SOD)值降低。相反,肝功能的酶活性(AST,ALT,ALP,细胞色素P450和肝葡萄糖-6-磷酸酶),脂质过氧化(MDA),促炎细胞因子(IL-1β,TNF-α,和IL-6),一氧化氮(NO)和炎症标志物(CRP)增强与STZ给药,在TQ治疗后基本上恢复。相对于糖尿病大鼠,TQ重建了肝脏结构变化和胶原纤维。此外,TQ下调了促凋亡标志物(caspase-3)的免疫组织化学染色的强度,肝组织中的p53和肿瘤坏死因子-α(TNF-α)蛋白。此外,TQ表现出相互作用和抑制caspase-3,白细胞介素-6受体的结合位点的能力,白细胞介素-1受体1型,TNF受体超家族成员1A,和TNF受体超家族成员1B在大鼠分子对接建模后。所有这些数据重建了肝功能,抗氧化酶,抗炎标志物,以及TQ对STZ诱导的DM大鼠的抗凋亡蛋白的影响。基于这些结果,实验表明,TQ是一种具有多种临床应用的新型天然补充剂,包括管理DM,反过来,建议在预防糖尿病的进展中起关键作用。
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