Hesperidin alleviates chronic restraint stress and lipopolysaccharide-induced Hippocampus and Frontal cortex damage in mice: Role of TLR4/NF-κB, p38 MAPK/JNK, Nrf2/ARE signaling
Hesperidin alleviates chronic restraint stress and lipopolysaccharide-induced Hippocampus and Frontal cortex damage in mice: Role of TLR4/NF-κB, p38 MAPK/JNK, Nrf2/ARE signaling
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DOI：
10.1016/j.neuint.2020.104835
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发表时间：
2020-11-01
影响因子：
4.2
通讯作者：
Naidu, V. G. M.
中科院分区：
文献类型：
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作者：
Kwatra, Mohit;Ahmed, Sahabuddin;Naidu, V. G. M.
应激和脂多糖(LPS)动物模型被用于筛选抗抑郁和抗焦虑药物。然而，它们的结合(束缚应激；RS和内毒素)对炎症、细胞凋亡和抗氧化信号的影响尚不清楚。本研究观察了RS+内毒素诱导的小鼠海马区(HIP)和额叶皮质(FC)的神经行为和神经化学异常。此外，柑橘黄酮苷(橙皮苷；HSP)的神经保护作用也在该模型中得到证实。雄性Balb/c小鼠给予RS(连续28天)和内毒素(单次剂量，0.83 mg/kg，ip)。在第28天。通过高架迷宫(EPM)、旷场试验(OFT)、明暗箱试验(OFT)、悬尾试验(TST)、强迫游泳试验(FST)、蔗糖偏爱试验(SPT)等方法评价RS+内毒素攻击对小鼠神经行为的影响。RS+LPS可通过增加氧化亚硝化应激，降低抗氧化剂GSH、SOD、CAT水平，增加氧化亚硝化应激、促炎细胞因子水平，增加IBA-1、GFAP、TLR4/NF-kappa B、p38MAPK/JNK，降低Nrf2/BDNF/HO-1在HIP和FC中的表达。第21天(第8~28天)，热休克蛋白(50和100 mg/kg，P.O.)治疗明显减轻焦虑和抑郁样行为，逆转神经化学和组织病理学改变。热休克蛋白通过其抗炎、抗凋亡、抗氧化和神经再生潜能发挥神经保护作用，可单独治疗精神疾病或与其他疾病相关。
Stress and lipopolysaccharide (LPS) animal models are used for screening antidepressants and anxiolytic drugs. However, the lacunae for their combination (Restraint stress; RS and LPS) impacting inflammation, apoptosis and antioxidant signaling have not been explored. The present study investigated RS + LPS-induced neurobehavioral and neurochemical anomalies in hippocampus (HIP) and frontal cortex (FC) of mice. Furthermore, citrus-derived flavanone glycoside (Hesperidin; HSP) neuroprotective ability was also confirmed in this model. Male Balb/c mice were given RS (for 28 days) and LPS (single dose, 0.83 mg/kg, i.p.) on 28th day. RS + LPS challenge caused neurobehavioral deficits in mice as evaluated over elevated plus maze (EPM), open field test (OFT), light-dark box test, tail suspension test (TST), forced swim test (FST), sucrose preference test (SPT). Moreover, RS + LPS caused alteration via enhanced oxido-nitrosative stress, proinflammatory cytokines level (serum, HIP, FC), lower antioxidants (GSH, SOD, CAT), increased IBA-1, GFAP, TLR4/NF-kappa B, p38MAPK/JNK while decreased Nrf2/BDNF/HO-1 expression in HIP and FC of mice. The 21 days (8-28th day), HSP (50 and 100 mg/kg, p.o.) treatment significantly alleviated the anxiety and depressive-like behavior and reversed neurochemical, histopathological changes. HSP exerted the neuroprotective effect via its anti-inflammatory, anti-apoptotic, antioxidant and neurogenesis potential in treating psychiatric illness alone or associated with other diseases.