It has been recently demonstrated that rosmarinic acid (RA) through modulation in the amyloidogenic pathway exhibit neuroprotective potential in Alzheimer’s disease. However, its effects on non-amyloidogenic pathways such as neuroinflammation (NI) and oxidative stress have not been elucidated carefully. Hence, this study aimed to investigate the effect of RA on cognitive function, cortical and hippocampal oxidant-antioxidant balance, and proinflammatory cytokines production in lipopolysaccharide (LPS)-induced NI in rats. NI was induced by intracerebroventricular injection of LPS (50 μg/20 μL; 10 μL into each ventricle) in Wistar rats. RA (25 and 50 mg/kg.) was intraperitoneally administrated to the experimental groups 30 min before the LPS injection and continued once per day for seven days. Cognitive function was investigated by the Y-maze test, and the production of proinflammatory cytokines and oxidative stress markers were evaluated in their hippocampi (HIP) and prefrontal cortex (PFC). In addition, neuronal damage was evaluated in the HIP subfields histologically. The RA administration could alleviate cognitive impairments caused by NI in LPS-treated rats as evidenced by improved working memory and attenuated neuronal injury in the HIP subfields. RA treatment in a dose-dependent manner prevented the overproduction of tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and IL-6 in both the HIP and PFC. RA significantly alleviated the HIP and PFC levels of malondialdehyde (MDA) and nitric oxide (NOx) and enhanced the superoxide dismutase (SOD) activity. These findings demonstrated that RA could also exert its neuroprotective effects by modulating non-amyloidogenic pathways such as inflammation and oxidative stress.

最近已经证明迷迭香酸 (RA) 通过调节淀粉样蛋白生成途径在阿尔茨海默病中表现出神经保护潜力。然而，其对神经炎症 (NI) 和氧化应激等非淀粉样蛋白生成途径的影响尚未得到仔细阐明。因此，本研究旨在研究 RA 对脂多糖 (LPS) 诱导的大鼠 NI 的认知功能、皮质和海马氧化-抗氧化平衡以及促炎细胞因子产生的影响。在 Wistar 大鼠中，通过脑室内注射 LPS（50 μg/20 μL；每个脑室 10 μL）诱导 NI。RA（25 和 50 mg/kg.）在 LPS 注射前 30 分钟向实验组腹膜内给药，每天一次，持续 7 天。通过 Y 迷宫测试研究认知功能，并且在他们的海马（HIP）和前额叶皮层（PFC）中评估了促炎细胞因子和氧化应激标志物的产生。此外，对 HIP 亚区的神经元损伤进行了组织学评估。RA 给药可以减轻 NI 在 LPS 治疗的大鼠中引起的认知障碍，这可以通过改善工作记忆和减轻 HIP 亚区的神经元损伤来证明。RA 治疗以剂量依赖性方式防止了 HIP 和 PFC 中肿瘤坏死因子-α (TNF-α)、白细胞介素 1β (IL-1β) 和 IL-6 的过量产生。RA显着减轻丙二醛（MDA）和一氧化氮（NOx）的HIP和PFC水平，并增强超氧化物歧化酶（SOD）活性。