神经炎症包括中枢神经系统中免疫胶质细胞的激活,释放促炎细胞因子,破坏正常的神经功能并导致各种神经系统疾病,包括阿尔茨海默病(AD),帕金森病,多发性硬化症,和中风。AD的特征是多种因素,包括淀粉样蛋白生成,突触功能障碍,记忆障碍和神经炎症。脂多糖(LPS)是革兰氏阴性细菌细胞膜的重要组成部分,引发剧烈的神经炎症并促进神经变性。Lupeol,一种天然存在的五环三萜,已经证明了几种药理特性,尤其是它的抗炎活性。在这项研究中,我们在脂多糖(LPS)注射的小鼠模型中评估了羽扇豆醇的抗炎和抗阿尔茨海默病活性。向C57BL/6N雄性小鼠腹膜内施用LPS(250ug/kg)1周以诱导神经炎症和认知障碍。对于生化分析,乙酰胆碱酯酶(AChE)测定,进行蛋白质印迹和共聚焦显微镜检查.AChE,Westernblot和免疫荧光结果显示,羽扇豆醇(50mg/kg)与LPS的同时显著抑制LPS诱导的神经炎症介质和核因子(NF-κB)等细胞因子的活化,肿瘤坏死因子(TNF-α),环氧合酶(COX-2)和白细胞介素(IL-1β)。此外,我们发现,LPS诱导的全身性炎症导致阿尔茨海默症的症状,因为LPS治疗提高了淀粉样β(Aβ)的水平,淀粉样前体蛋白(APP),β-位点APP裂解酶(BACE-1)和过度磷酸化Tau(p-Tau)。羽扇豆醇治疗逆转了LPS诱导的Aβ水平升高,APP,海马中的BACE-1和p-Tau,显示抗阿尔茨海默氏症的特性。还确定了羽扇豆醇通过增强突触前和突触后标志物如SNAP-23、突触素和PSD-95的表达来预防LPS诱导的突触功能障碍。总的来说,我们的研究表明,羽扇豆醇通过抑制神经炎症过程来预防记忆障碍和突触功能障碍。因此,我们建议羽扇豆醇可能是预防神经炎症引起的神经疾病如AD的有用治疗剂。
Neuroinflammation includes the activation of immune glial cells in the central nervous system, release pro-inflammatory cytokines, which disrupt normal neural function and contribute to various neurological disorders, including Alzheimer\'s disease (AD), Parkinson\'s disease, multiple sclerosis, and stroke. AD is characterized by various factors including amyloidogenesis, synaptic dysfunction, memory impairment and neuroinflammation. Lipopolysaccharide (LPS) constitutes a vital element of membrane of the gram-negative bacterial cell, triggering vigorous neuroinflammation and facilitating neurodegeneration. Lupeol, a naturally occurring pentacyclic triterpene, has demonstrated several pharmacological properties, notably its anti-inflammatory activity. In this study, we evaluated the anti-inflammatory and anti-Alzheimer activity of lupeol in lipopolysaccharide (LPS)-injected mice model. LPS (250ug/kg) was administered intraperitoneally to C57BL/6 N male mice for 1 week to induce neuroinflammation and cognitive impairment. For biochemical analysis, acetylcholinesterase (AChE) assay, western blotting and confocal microscopy were performed. AChE, western blot and immunofluorescence results showed that lupeol treatment (50 mg/kg) along with LPS administration significantly inhibited the LPS-induced activation of neuroinflammatory mediators and cytokines like nuclear factor (NF-κB), tumor necrosis factor (TNF-α), cyclooxygenase (COX-2) and interleukin (IL-1β). Furthermore, we found that LPS-induced systemic inflammation lead to Alzheimer\'s symptoms as LPS treatment enhances level of amyloid beta (Aβ), amyloid precursor protein (APP), Beta-site APP cleaving enzyme (BACE-1) and hyperphosphorylated Tau (p-Tau). Lupeol treatment reversed the LPS-induced elevated level of Aβ, APP, BACE-1 and p-Tau in the hippocampus, showing anti-Alzheimer\'s properties. It is also determined that lupeol prevented LPS-induced synaptic dysfunction via enhanced expression of pre-and post-synaptic markers like SNAP-23, synaptophysin and PSD-95. Overall, our study shows that lupeol prevents memory impairment and synaptic dysfunction via inhibition of neuroinflammatory processes. Hence, we suggest that lupeol might be a useful therapeutic agent in prevention of neuroinflammation-induced neurological disorders like AD.