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 28^th 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-κB, p38MAPK/JNK while decreased Nrf2/BDNF/HO-1 expression in HIP and FC of mice. The 21 days (8–28^th 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.

应激和脂多糖 (LPS) 动物模型用于筛选抗抑郁药和抗焦虑药。然而，尚未探索其组合（约束应激；RS 和 LPS）影响炎症、细胞凋亡和抗氧化信号的缺陷。本研究调查了 RS + LPS 诱导的小鼠海马 (HIP) 和额叶皮层 (FC) 的神经行为和神经化学异常。此外，在该模型中还证实了柑橘衍生的黄烷酮糖苷（橙皮苷；HSP）的神经保护能力。雄性Balb / c小鼠进行RS（28天）和在第28 LPS（单次剂量，0.83毫克/公斤，腹腔注射）^第日。RS + LPS 攻击导致小鼠神经行为缺陷，如通过高架十字迷宫 (EPM)、开放场测试 (OFT)、明暗盒测试、悬尾测试 (TST)、强迫游泳测试 (FST)、蔗糖偏好测试进行评估。 SPT）。此外，RS + LPS 通过增强氧化亚硝化应激、促炎细胞因子水平（血清、HIP、FC）、降低抗氧化剂（GSH、SOD、CAT）、增加 IBA-1、GFAP、TLR4/NF-κB、p38MAPK/ JNK 同时降低小鼠 HIP 和 FC 中 Nrf2/BDNF/HO-1 的表达。第 21 天（^第8-28 天）天），HSP（50 和 100 毫克/千克，口服）治疗显着减轻了焦虑和抑郁样行为，并逆转了神经化学、组织病理学变化。HSP通过其抗炎、抗细胞凋亡、抗氧化和神经发生潜力在单独治疗精神疾病或与其他疾病相关的精神疾病中发挥神经保护作用。