Honokiol abrogates lipopolysaccharide-induced depressive like behavior by impeding neuroinflammation and oxido-nitrosative stress in mice
Honokiol abrogates lipopolysaccharide-induced depressive like behavior by impeding neuroinflammation and oxido-nitrosative stress in mice
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DOI：
10.1016/j.ejphar.2014.09.049
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发表时间：
2014-12-05
影响因子：
5
通讯作者：
Lahkar, Mangala
中科院分区：
文献类型：
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作者：
Sulakhiya, Kunjbihari;Kumar, Parveen;Lahkar, Mangala
抑郁症是一种炎症性、常见和致命的精神疾病，具有很高的终生患病率。临床前和临床研究表明，免疫-炎症和氧化-亚硝化应激通路的激活在抑郁症的病理生理中起重要作用。檀香木脂素（Honokaline，HNK）是一种具有抗氧化、抗炎、抗焦虑、抗抑郁和神经保护等多种生物活性的双胎盘新木脂素。本研究考察了HNK（2.5和5 mg/kg，i. p.）预处理（LPS前30分钟）的脂多糖（LPS）（0.83 mg/kg，i. p.）在小鼠中诱导抑郁样行为、神经炎症和氧化-亚硝化应激。HNK预处理可显著降低LPS诱导的抑郁样行为，减少强迫游泳和悬尾实验中的不动时间，改善蔗糖偏好实验中的快感缺失行为。HNK预处理通过降低海马（HC）和前额叶皮质（PFC）中IL-1 β、IL-6和TNE-α的水平来减轻LPS诱导的神经炎症。HNK预处理可通过提高HC和PFC中还原型谷胱甘肽水平沿着降低脂质过氧化和亚硝酸盐水平来预防LPS引起的氧化/亚硝化应激，并可预防LPS攻击小鼠血浆皮质酮（CORT）水平的升高和海马骨水平的降低。总之，目前的研究表明，FINK预处理提供了对LPS诱导的抑郁样行为的保护，这可能是通过抑制促炎细胞因子以及氧化亚硝化应激介导的HC和PFC。我们的研究结果强烈推测，FINK可能是一种治疗抑郁症和其他病理生理条件，这是密切相关的神经炎症和氧化亚硝化应激的治疗方法。(C)2014 Elsevier By.版权所有© 2016
Depression is an inflammatory, commonly occurring and lethal psychiatric disorder having high lifetime prevalence. Preclinical and clinical studies suggest that activation of immuno-inflammatory and oxido-nitrosative stress pathways play major role in the pathophysiology of depression. Honokiol (HNK) is a biplacnolic neolignan possessing multiple biological activities including antioxidant, anti-inflammatory, anxiolytic, antidepressant and neuroprotective. The present study investigated the effect of HNK (2.5 and 5 mg/kg, i.p.) pretreatment (30 min prior to LPS) on lipopolysaccharide (LPS) (0.83 mg/kg, i.p.) induced depressive like behavior, neuroinflammation, and oxido-nitrosative stress in mice. HNK pretreatment at both the doses significantly attenuated LPS induced depressive-like behavior by reducing the immobility time in forced swim and tail suspension test, and by improving the anhedonic behavior observed in sucrose preference test. HNK pretreatment ameliorated LPS induced neuroinflammation by reducing IL-1 beta, lL-6 and TNE-alpha level in hippocampus (HC) and prefrontal cortex (PFC). HNK pretreatment prevented LPS evoked oxidative/nitrosative stress via improving reduced glutathione level along with reduction in the lipid peroxiclation and nitrite level in HC and PFC. Pretreatment with HNK also prevented the increase in plasma corticosterone (CORT) and decrease in hippocampal BONE level in LPS challenged mice. In conclusion, current investigation suggested that FINK pretreatment provided protection against LPS-induced depressive like behavior which may be mediated by repression of pro-inflammatory cytokines as well as oxido-nitrosative stress in HC and PFC. Our results strongly speculated that FINK could be a therapeutic approach for the treatment of depression and other pathophysiological conditions which are closely associated with neuroinflammation and oxido-nitrosative stress. (C) 2014 Elsevier By. All rights reserved,