Department of Pharmacology, Sinhgad Institute of Pharmaceutical Sciences, Lonavala, Pune, 410401, India; Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, 382 481, Gujarat, India.
Department of Pharmacology, Sinhgad Institute of Pharmaceutical Sciences, Lonavala, Pune, 410401, India; RMD Institute of Pharmaceutical Education & Research, Pune, 411019, Maharashtra, India.
Eur J Pharmacol. 2021 May 5;898:173992. doi: 10.1016/j.ejphar.2021.173992. Epub 2021 Mar 3.
Amelioration of oxidative stress via promoting the endogenous antioxidant system and enhancement of monoamines in brain were the important underlying antidepressant mechanism of protocatechuic acid (PCA). The aim of the present study is to explore the potential antidepressant mechanism(s) PCA in chronic unpredictable mild stress (CUMS) mice. Mice were subjected to CUMS protocol for 4 weeks, and administered with PCA (100 and 200 mg/kg) and fluoxetine (20 mg/kg) for 24 days (from day 8th to 31st). Behavioral (sucrose preference, immobility time, exploratory behavior), and biochemical alterations such as serum corticosterone, brain derived neurotrophic factor (BDNF), inflammatory cytokines, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), and antioxidants parameters were investigated. Experimental findings revealed that CUMS subjected mice exhibited significant impairment in behavioral alterations, such as increased immobility time, impaired preference to the sucrose solution, BDNF levels and, serum corticosterone, cytokines, malondialdehyde (MDA) formation with impaired antioxidants in the hippocampus and cerebral cortex. Administration of PCA to CUMS mice attenuated the immobility time, serum corticosterone, cytokines TNF-α, and IL-6, MDA formation and improved sucrose preference, including restoration of BDNF level. Thus, the present findings demonstrated the antidepressant potential of PCA which is largely achieved probably through maintaining BDNF level, and by modulation of the oxidative stress response, cytokines systems, and antioxidant defense system in mice.
通过促进内源性抗氧化系统和增强大脑中的单胺类物质来改善氧化应激，是原儿茶酸（PCA）发挥抗抑郁作用的重要潜在机制。本研究旨在探索 PCA 对慢性不可预测轻度应激（CUMS）小鼠的潜在抗抑郁机制。将小鼠进行 CUMS 方案处理 4 周，并给予 PCA（100 和 200mg/kg）和氟西汀（20mg/kg）治疗 24 天（第 8 天至第 31 天）。检测行为（糖水偏好、不动时间、探索行为）和生化变化，如血清皮质酮、脑源性神经营养因子（BDNF）、炎性细胞因子、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和抗氧化参数。实验结果表明，CUMS 处理的小鼠表现出明显的行为改变，如不动时间增加、糖水偏好降低、BDNF 水平降低，血清皮质酮、细胞因子 TNF-α和 IL-6、海马和大脑皮质丙二醛（MDA）形成增加，抗氧化能力受损。给予 PCA 治疗可减轻 CUMS 小鼠的不动时间、血清皮质酮、细胞因子 TNF-α和 IL-6、MDA 形成，并改善糖水偏好，包括恢复 BDNF 水平。因此，本研究结果表明 PCA 具有抗抑郁作用，其机制可能主要通过维持 BDNF 水平，并通过调节氧化应激反应、细胞因子系统和抗氧化防御系统来实现。
