Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Department of Pharmacology, Pharmacy Program, Oman College of Health Sciences, 114, Muscat, Oman.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Aug;393(8):1391-1404. doi: 10.1007/s00210-020-01838-w. Epub 2020 Feb 20.
Diabetes mellitus and depression are comorbid diseases affecting many patients all over the world. The current study was designed to compare the antidepressant effect of some antidiabetic drugs such as vildagliptin, pioglitazone, glyburide, and metformin on depression-related or unrelated to type 2 diabetes mellitus (T2DM). T2DM was induced by high-fat diet and streptozotocin, while diabetes-unrelated depression was induced by reserpine. Antidiabetic agents reduced diabetes-associated depression as indicated by the reduction in the immobility time in the forced swim test, elevation of cortical and hippocampal serotonin and brain-derived neurotrophic factor (BDNF), and the increase in serum β-Amyloid 1-42 (Aβ1-42) levels. Antidiabetic agents also reduced serum corticosterone levels suggesting their inhibitory effect on hypothalamus-pituitary-adrenal axis activity. The antidepressant activity of the tested compounds was associated with reduction of oxidative stress and inflammation in brain. Vildagliptin showed the highest, while glyburide showed the least antidiabetic and antidepressant activity. Antidepressant activities of pioglitazone and metformin were comparable. The difference in antioxidant and anti-inflammatory activities between groups showed the same pattern of the antidepressant effect suggesting that these two pathways may play role in ameliorating depression in diabetic rats. On the other hand, the administration of reserpine in small doses (0.2 mg/kg) induced depression associated with hyperglycemia in non-diabetic rats. Although all treatments improved glycemic parameters to similar levels, vildagliptin showed the greatest effect on Aβ1-42, serotonin, norepinephrine, and BDNF levels. In conclusion, vildagliptin seems to be the leading drug among the tested antidiabetics and may be the most appropriate antidiabetic for managing diabetes-associated depression.
糖尿病和抑郁症是影响全球许多患者的共病。本研究旨在比较几种抗糖尿病药物（如维格列汀、吡格列酮、格列美脲和二甲双胍）对与 2 型糖尿病（T2DM）相关或不相关的抑郁症的抗抑郁作用。T2DM 是通过高脂肪饮食和链脲佐菌素诱导的，而与糖尿病无关的抑郁症是通过利血平诱导的。抗糖尿病药物通过减少强迫游泳试验中的不动时间、提高皮质和海马中的 5-羟色胺和脑源性神经营养因子（BDNF）水平以及增加血清 β-淀粉样蛋白 1-42（Aβ1-42）水平来减轻与糖尿病相关的抑郁症。抗糖尿病药物还降低了血清皮质酮水平，表明它们对下丘脑-垂体-肾上腺轴活动有抑制作用。测试化合物的抗抑郁活性与减轻大脑中的氧化应激和炎症有关。维格列汀的作用最强，而格列美脲的作用最弱。吡格列酮和二甲双胍的抗抑郁活性相当。各组之间抗氧化和抗炎活性的差异表现出与抗抑郁作用相同的模式，表明这两种途径可能在改善糖尿病大鼠的抑郁方面发挥作用。另一方面，小剂量（0.2mg/kg）利血平给药会导致非糖尿病大鼠出现与高血糖相关的抑郁。尽管所有治疗都使血糖参数改善到相似水平，但维格列汀对 Aβ1-42、5-羟色胺、去甲肾上腺素和 BDNF 水平的影响最大。总之，维格列汀似乎是测试抗糖尿病药物中的主导药物，可能是治疗与糖尿病相关的抑郁症的最佳抗糖尿病药物。
