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Protective Effects of Phyllanthus amarus Against Lipopolysaccharide-Induced Neuroinflammation and Cognitive Impairment in Rats

机译：Ph叶对脂多糖诱导的大鼠神经炎症和认知障碍的保护作用

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>Background: Phyllanthus amarus (PA) is widely studied for its hepatoprotective properties but has recently received increasing attention due to its diverse anti-inflammatory effects. However, the effects of PA in modulating immune responses in the central nervous system leading to protection against functional changes remain unexplored. Therefore, we sought to examine the protective effects of 80% v/v ethanol extract of PA on lipopolysaccharide (LPS)-induced non-spatial memory impairment and neuroinflammation. >Methods: Selected major phytoconstituents of PA extract were identified and quantified using high-performance liquid chromatography. Subchronic neurotoxicity was performed in male Wistar rats given daily oral administration of 100, 200, and 400 mg/kg of the PA extract. Their neurobehavioral activities (functional observation battery and locomotor activity) were scored, and the extracted brains were examined for neuropathological changes. Rats were treated orally with vehicle (5% Tween 20), PA extract (100, 200, and 400 mg/kg), or ibuprofen (IBF; 40 mg/kg) for 14 and 28 days before being subjected to novel object discrimination test. All groups were challenged with LPS (1 mg/kg) given intraperitoneally a day prior to the behavioral tests except for the negative control group. At the end of the behavioral tests, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, nitric oxide (NO), inducible nitric oxide synthase (iNOS), CD11b/c integrin expression, and synaptophysin immunoreactivity were determined in the brain tissues. >Results: Gallic acid, ellagic acid, corilagin, geraniin, niranthin, phyllanthin, hypophyllanthin, phyltetralin, and isonirtetralin were identified in the PA extract. Subchronic administration of PA extract (100, 200, and 400 mg/kg) showed no abnormalities in neurobehavior and brain histology. PA extract administered at 200 and 400 mg/kg for 14 and 28 days effectively protected the rodents from LPS-induced memory impairment. Similar doses significantly (p < 0.05) decreased the release of proteins like TNF-α, IL-1β, and iNOS in the brain tissue. NO levels, CD11b/c integrin expression, and synaptophysin immunoreactivity were also reduced as compared with those in the LPS-challenged group. >Conclusion: Pre-treatment with PA extract for 14 and 28 days was comparable with pre-treatment with IBF in prevention of memory impairment and alleviation of neuroinflammatory responses induced by LPS. Further studies are essential to identify the bioactive phytochemicals and the precise underlying mechanisms.
机译：>背景：苦竹（Phyllanthus amarus，PA）具有保护肝脏的特性，但由于其多种抗炎作用，最近受到越来越多的关注。然而，PA在调节中枢神经系统中导致抵抗功能改变的免疫反应中的作用尚待探索。因此，我们试图检查PA的80％v / v乙醇提取物对脂多糖（LPS）诱导的非空间记忆障碍和神经炎症的保护作用。 >方法：使用高效液相色谱法对PA提取物中的主要植物成分进行鉴定和定量。每天口服100、200和400 mg / kg的PA提取物，在雄性Wistar大鼠中进行亚慢性神经毒性。对他们的神经行为活动（功能观察电池和运动活动）进行评分，并对提取的大脑进行神经病理学检查。在接受新的物体识别测试之前，先对大鼠口服赋形剂（5％Tween 20），PA提取物（100、200和400 mg / kg）或布洛芬（IBF； 40 mg / kg）治疗14天和28天。 。除阴性对照组外，在行为测试前一天，所有组均接受腹膜内给予LPS（1 mg / kg）的攻击。在行为测试结束时，检测到肿瘤坏死因子-α（TNF-α），白介素（IL）-1β，一氧化氮（NO），诱导型一氧化氮合酶（iNOS），CD11b / c整合素表达和在脑组织中确定突触素免疫反应性。 >结果：在PA提取物中鉴定出了没食子酸，鞣花酸，可乐可宁，香叶素，烟碱，菲兰新素，次叶鲜黄素，叶四氢化萘和异四氢化萘。 PA提取物（100、200和400 mg / kg）的亚慢性给药显示神经行为和脑组织学无异常。 PA提取物以200和400 mg / kg的剂量给药14天和28天有效地保护了啮齿动物免受LPS诱导的记忆障碍。相似剂量显着（p <0.05）减少了脑组织中TNF-α，IL-1β和iNOS等蛋白质的释放。与LPS激发组相比，NO水平，CD11b / c整联蛋白表达和突触素免疫反应性也降低。 >结论：在预防记忆障碍和减轻LPS引起的神经炎反应方面，PA提取物预处理14天和28天与IBF预处理相当。进一步的研究对于确定生物活性植物化学物质及其确切的潜在机制至关重要。

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