Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Department of Pharmaceutical Chemistry, School of Pharmaceutical Education & Research, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Biomed Pharmacother. 2017 Nov;95:1232-1241. doi: 10.1016/j.biopha.2017.09.014. Epub 2017 Oct 6.
Emerging evidence suggests that thiazole compounds are of great interest due to their protective effect against DM. Protective effects of thiazole derivatives against hyperglycemia have been demonstrated in earlier in vitro and in vivo studies. Previously, anti-oxidant and free radical scavenging activities of 2-(4-Fluorobenzamido)-4-methylthiazole-5-carboxylicacid, a newly developed thiazole derivative (NDTD), have been well-documented. Current study investigated the pharmacological effect of NDTD on hyperglycaemia, insulin sensitivity, lipid profile, anti-inflammatory and oxidative stress markers in an animal model. T2DM was induced in neonatal rats using single i.p. injection of STZ at a dose of 100mg/kg. As a result, significant increase in serum glucose, insulin and HOMA-IR, lipid and pro-inflammatory cytokines levels were observed in STZ diabetic rats compared to normal control rats. Administration of NDTD for 4 weeks reversed the increased levels of above mentioned parameters to normal. Increased serum TG, TC, LDL-C and VLDL-C levels were significantly lowered, while reduction of serum HDL-C was alleviated after administration of NDTD. In addition, NDTD attenuated oxidative stress markers by increasing levels of GSH, CAT, SOD and lowering the level of MDA. Similarly, NDTD showed its pharmacological effects against hepatic and renal injury markers via restoring the alleviated level of ALT, AST, BUN, CRE and uric acid. In addition, all the results obtained from the biochemical estimations were supported by the histopathological examination. Pancreatic histopathological study demonstrated reduction in the size of pancreatic islets as well as the number of β-cells, per islet in the STZ control group and diabetic rats exposed to NDTD normalized the morphology of islets. Furthermore, histopathological study of liver suggests the protective role of NDTD against hepatic injury, as diabetic rats exposed with NDTD shows significantly reduction in inflammation and lesion as compared to STZ control rats. Our findings concluded, NDTD attenuated hyperglycaemia, glucose intolerance and insulin resistance through its anti-oxidant and anti-inflammatory effects. Thus, we suggest NDTD as potential therapeutic candidate for T2DM. In addition, the current study also investigated the beneficial effects of NDTD against inflammation, hyperlipidemia, renal and hepatic injury.
新兴证据表明,噻唑类化合物因其对糖尿病的保护作用而备受关注。噻唑衍生物在体外和体内早期研究中已被证明具有抗高血糖作用。先前,一种新开发的噻唑衍生物(NDTD)的 2-(4-氟苯甲酰胺基)-4-甲基噻唑-5-羧酸的抗氧化和自由基清除活性已有详细记录。本研究旨在探讨 NDTD 对糖尿病模型中高血糖、胰岛素敏感性、血脂谱、抗炎和氧化应激标志物的药理作用。通过单次腹腔注射 STZ(剂量为 100mg/kg)诱导新生大鼠 T2DM。结果显示,与正常对照组大鼠相比,STZ 糖尿病大鼠的血清葡萄糖、胰岛素和 HOMA-IR、血脂和促炎细胞因子水平显著升高。NDTD 治疗 4 周可使上述参数升高恢复正常。NDTD 可降低血清 TG、TC、LDL-C 和 VLDL-C 水平,减轻血清 HDL-C 降低。此外,NDTD 通过增加 GSH、CAT、SOD 水平和降低 MDA 水平来减轻氧化应激标志物。同样,NDTD 通过恢复 ALT、AST、BUN、CRE 和尿酸减轻的水平,对肝肾功能损伤标志物表现出其药理作用。此外,所有生化测定结果均得到组织病理学检查的支持。胰腺组织病理学研究表明,STZ 对照组和接受 NDTD 治疗的糖尿病大鼠的胰岛体积和每个胰岛的β细胞数量减少,NDTD 使胰岛形态正常化。此外,肝组织病理学研究表明,NDTD 具有抗肝损伤作用,因为与 STZ 对照组大鼠相比,接受 NDTD 治疗的糖尿病大鼠的炎症和病变明显减少。我们的研究结果表明,NDTD 通过其抗氧化和抗炎作用减轻高血糖、葡萄糖耐量和胰岛素抵抗。因此,我们认为 NDTD 是 T2DM 的潜在治疗候选药物。此外,本研究还探讨了 NDTD 对炎症、高脂血症、肾和肝损伤的有益作用。