Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
J Neuroimmune Pharmacol. 2017 Jun;12(2):277-291. doi: 10.1007/s11481-016-9712-7. Epub 2016 Oct 11.
Depression is a major health problem in which oxidative stress and inflammation are inextricably connected in its pathophysiology. Coenzyme Q10 (CoQ10) is an important anti-oxidant compound with anti-inflammatory and neuro-protective properties. This study was designed to investigate the hypothesis that CoQ10 by its anti-oxidant and anti-inflammatory potentials can alleviate depressive- like behavior by restoring the balance of the tryptophan catabolites kynurenine/serotonin toward the serotonin pathway by down-regulation of hippocampal indoleamine 2,3-dioxygenase 1 (IDO-1). Depressive-like behavior was induced by chronic unpredictable mild stress (CUMS) protocol including food or water deprivation, cage tilting, reversed light cycle etc. Male Wistar rats were randomly divided into five groups; Control, CUMS, CUMS and CoQ10 (50,100 and 200 mg/kg/day i.p. respectively) groups. CoQ10 effects on different behavioral and biochemical tests were analyzed. CoQ10 showed significant antidepressant efficacy, as evidenced by significantly decreased stress induced changes to forced swimming challenge and open field test, as well as attenuating raised corticosterone level and adrenal glands weight. The anti-oxidant effect of CoQ10 was exhibited by its ability to significantly reduce hippocampal elevated malondialdehyde and 4-hydroxynonenal levels and elevate the reduced glutathione and catalase levels. CoQ10 significantly reduced different pro-inflammatory cytokines levels including interleukin (IL)-1β, IL-2, IL-6 and tumor necrosis factor-α. It suppressed hippocampal IDO-1 and subsequent production of kynurenine and enhanced the hippocampal contents of tryptophan and serotonin. Immunohistochemical analysis revealed that CoQ10 was able to attenuate the elevated microglial CD68 and elevate the astrocyte glial fibrillary acidic protein compared to CUMS group. CoQ10 exhibited antidepressant-like effects on rats exposed to CUMS. This could be attributed to its ability to reduce IDO-1 leading to shift the balance of the Kynurenine/ serotonin toward the serotonin pathway.
抑郁症是一种主要的健康问题，其病理生理学中氧化应激和炎症是密不可分的。辅酶 Q10（CoQ10）是一种具有抗氧化、抗炎和神经保护特性的重要抗氧化化合物。本研究旨在验证 CoQ10 通过其抗氧化和抗炎特性，通过下调海马吲哚胺 2,3-双加氧酶 1（IDO-1），可以恢复色氨酸代谢物犬尿氨酸/血清素向血清素途径的平衡，从而减轻抑郁样行为的假设。抑郁样行为是通过慢性不可预测轻度应激（CUMS）方案诱导的，包括食物或水剥夺、笼倾斜、光照周期颠倒等。雄性 Wistar 大鼠随机分为五组；对照组、CUMS 组、CUMS 和 CoQ10（分别为 50、100 和 200mg/kg/天腹腔注射）组。分析了 CoQ10 对不同行为和生化测试的影响。CoQ10 表现出明显的抗抑郁作用，表现在强迫游泳挑战和旷场试验中，应激诱导的变化明显减少，以及皮质酮水平和肾上腺重量升高得到缓解。CoQ10 的抗氧化作用表现为其能够显著降低海马升高的丙二醛和 4-羟壬烯醛水平，并提高还原型谷胱甘肽和过氧化氢酶水平。CoQ10 显著降低了包括白细胞介素（IL）-1β、IL-2、IL-6 和肿瘤坏死因子-α在内的不同促炎细胞因子水平。它抑制了海马 IDO-1 及其随后产生的犬尿氨酸，并增加了海马色氨酸和血清素的含量。免疫组织化学分析显示，与 CUMS 组相比，CoQ10 能够减弱升高的小胶质细胞 CD68 并升高星形胶质细胞胶质纤维酸性蛋白。CoQ10 对暴露于 CUMS 的大鼠表现出抗抑郁样作用。这可能归因于其降低 IDO-1 的能力，从而导致犬尿氨酸/血清素平衡向血清素途径转移。
