The Department of Pharmacology, Egyptian Drug Authority, EDA, Formerly NODCAR, Giza, Egypt.
The Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Eur J Pharmacol. 2021 Dec 5;912:174602. doi: 10.1016/j.ejphar.2021.174602. Epub 2021 Oct 25.
Depression is a widespread, withering illness, resulting in a massive personal suffering and economic loss. The chronic exposure to stress may be involved in the etiology of human psychiatric disorders; such as depression. In the current study, the animals were subjected to chronic unpredictable mild stress (CUMS) for 14 days. Saxagliptin (SAXA) is a member of dipeptidyl peptidase-4 (DPP-4) inhibitors class. The current study was the first one to examine the anti-depressive effect of SAXA in an experimental model of CUMS-induced depression in rats and the possible underlying mechanisms. Animals were orally treated with SAXA (0.5, 1 and 2 mg/kg) for 14 days. SAXA treatment reversed the CUMS-induced alterations in the behavioral, biochemical as well as histopathological parameters. Moreover, it hindered the CUMS-induced increase in the oxidative stress, inflammatory, and apoptotic markers. On the other hand, it increased the monoamines levels and the neurogenic brain derived neurotrophic factor (BDNF). In addition, SAXA treatment increased the incretin hormones, glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which are linked to the activation of protein kinase B (AKT)/phosphatidylinositol3-kinase (PI3K) pathway. In conclusion, the current study revealed that the modulation of the interplay between the key events involved in depression, including oxidative stress, inflammation, and GLP-1/PI3K/AKT signaling pathway, can explain the anti-depressant activity of SAXA.
抑郁症是一种广泛存在、使人衰弱的疾病，会导致巨大的个人痛苦和经济损失。慢性应激暴露可能与人类精神障碍的病因有关；如抑郁症。在目前的研究中，动物被暴露于慢性不可预测的轻度应激（CUMS）14 天。沙格列汀（SAXA）是二肽基肽酶-4（DPP-4）抑制剂类的成员。目前的研究首次在 CUMS 诱导的抑郁大鼠实验模型中检查了 SAXA 的抗抑郁作用及其可能的潜在机制。动物被口服给予 SAXA（0.5、1 和 2mg/kg）14 天。SAXA 治疗逆转了 CUMS 引起的行为、生化和组织病理学参数的改变。此外，它阻止了 CUMS 引起的氧化应激、炎症和细胞凋亡标志物的增加。另一方面，它增加了单胺类物质水平和神经源性脑源性神经营养因子（BDNF）。此外，SAXA 治疗增加了肠促胰岛素激素，胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性胰岛素释放肽（GIP），这与蛋白激酶 B（AKT）/磷脂酰肌醇 3-激酶（PI3K）途径的激活有关。总之，目前的研究表明，调节涉及抑郁症的关键事件之间的相互作用，包括氧化应激、炎症和 GLP-1/PI3K/AKT 信号通路，可以解释 SAXA 的抗抑郁作用。
