Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Neurosurgery, Tabriz University of Medical Sciences, Tabriz, Iran; Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Life Sci. 2018 Nov 15;213:198-205. doi: 10.1016/j.lfs.2018.10.040. Epub 2018 Oct 21.
There is increasing evidence showing that mild traumatic brain injury (mTBI) is associated with increased depression-related disorders in humans. Recent studies suggest that dietary intake or supplementation of natural flavonoids like hesperidin can be used for therapy of patients with brain injury and depression. However, the exact mechanisms by which hesperidin indicates its neuroprotective effects are not fully understood. The purpose of this study was to explore the influence of hesperidin on depression-related symptoms in a mouse model of mTBI, and that what mechanisms are primarily involved in the antidepressant effects of this bioflavonoid.
Ten days after mTBI-induction, mice received oral hesperidin treatment (50 mg/kg/14 days), then animals were subjected to different depression tests including sucrose preference test, forced swim test, novelty-suppressed feeding test, and tail suspension test. We also measured levels of tumor necrosis factor (TNF)-α, interleukin-(IL)-1β, malondialdehyde (MDA), and brain-derived-neurotrophic-factor (BDNF) in the hippocampus.
Our results show that mTBI induction induced depressive-like behaviors in mice by increasing inflammatory cytokines (IL-1β and TNF-α) and oxidative stress marker (MDA), and reducing BDNF levels in the hippocampus. Interestingly, hesperidin treatment was effective to significantly reduce depression-related symptoms in mTBI-induced mice. In addition, hesperidin decreased the levels of IL-1β, TNF-α and MDA, and increased BDNF levels in the hippocampus. The major strength of our study is that four behavioral tests gave similar results.
This study suggests that the antidepressant-like effect of hesperidin may be mediated, at least in part, by decreased neuroinflammation and oxidative damage, and enhanced BDNF production in the hippocampus.
越来越多的证据表明，轻度创伤性脑损伤（mTBI）与人类中与抑郁相关的疾病增多有关。最近的研究表明，饮食摄入或补充橙皮苷等天然类黄酮可用于脑损伤和抑郁症患者的治疗。然而，橙皮苷发挥其神经保护作用的确切机制尚不完全清楚。本研究旨在探讨橙皮苷对 mTBI 小鼠模型中与抑郁相关症状的影响，以及这种生物类黄酮的抗抑郁作用主要涉及哪些机制。
mTBI 诱导 10 天后，小鼠接受口服橙皮苷治疗（50mg/kg/14 天），然后动物接受不同的抑郁测试，包括蔗糖偏好测试、强迫游泳测试、新异抑制性摄食测试和悬尾测试。我们还测量了海马中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、丙二醛（MDA）和脑源性神经营养因子（BDNF）的水平。
我们的结果表明，mTBI 诱导通过增加海马中的炎症细胞因子（IL-1β和 TNF-α）和氧化应激标志物（MDA）以及降低 BDNF 水平，导致小鼠出现抑郁样行为。有趣的是，橙皮苷治疗对 mTBI 诱导的小鼠的抑郁相关症状有效。此外，橙皮苷降低了海马中 IL-1β、TNF-α和 MDA 的水平，并增加了 BDNF 的水平。本研究的主要优势在于四项行为测试得出了相似的结果。
这项研究表明，橙皮苷的抗抑郁样作用可能至少部分通过减少海马中的神经炎症和氧化损伤以及增强 BDNF 的产生来介导。
