Phloridzin attenuates lipopolysaccharide-induced cognitive impairment via antioxidant, anti-inflammatory and neuromodulatory activities
Phloridzin attenuates lipopolysaccharide-induced cognitive impairment via antioxidant, anti-inflammatory and neuromodulatory activities
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DOI：
10.1016/j.cyto.2020.155408
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发表时间：
2021-01-18
期刊：
影响因子：
3.8
通讯作者：
Nakhate, Kartik T.
中科院分区：
文献类型：
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作者：
Kamdi, Sandesh P.;Raval, Amit;Nakhate, Kartik T.
背景：脂多糖（LPS）可引起神经炎症和记忆障碍。虽然根皮苷根皮苷（一种酚类植物成分）具有抗氧化和抗炎活性，但其对LPS介导的神经炎症和记忆功能障碍的改善作用尚未被探索。目的：研究根皮苷对LPS介导的小鼠记忆障碍和神经炎症的保护作用。通过腹膜内（ip）途径用LPS（250 μ g/kg）处理不同组小鼠以诱导认知障碍。分别给予根皮苷（10-20 mg/kg，口服）或多奈哌齐（1 mg/kg，腹腔注射），用Morris水迷宫（MWM）和Y-迷宫评价动物的记忆功能。行为学实验结束后处死动物，测定各组动物脑组织中乙酰胆碱酯酶（AChE）、脑源性神经营养因子（BDNF）、肿瘤坏死因子（TNF）等生化指标测定海马和大脑皮质中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的含量。虽然LPS给药的动物在MWM和Y迷宫中表现出显著降低的记忆保持，但在用根皮苷处理后观察到所有参数的显著逆转。LPS处理的动物显示海马和皮质中抗氧化剂（SOD和GSH）、神经营养因子（BDNF）和胆碱能传递（增加AChE）的水平显著降低，并且炎症/氧化标志物（TNF-α、IL-6和MDA）的水平增加。这些变化与根皮苷治疗后缓解。结论：根皮苷可能具有神经保护作用，对LPS诱导的神经炎症和记忆障碍凭借其抗氧化，抗炎，增强胆碱能信号在海马和大脑皮层的活动。
Background: Lipopolysaccharide (LPS) is known to produce neuroinflammation and memory impairment. Although phloridzin (a phenolic phytoconstituent) shows antioxidant- and anti-inflammatory activities, its ameliorative potential in LPS-mediated neuroinflammation and memory dysfunction remains unexplored.Objectives: To investigate the protective effect of phloridzin against LPS-mediated memory impairment and neuroinflammation in mice.Methods: Different groups of mice were treated with LPS (250 mu g/kg) via intraperitoneal (ip) route to induce cognitive impairments. The animals were administered with phloridzin (10-20 mg/kg, oral) or donepezil (1 mg/kg, intraperitoneal), and memory functions were evaluated by Morris water maze (MWM) and Y-maze. At the end of the behavioral experiments, the animals were sacrificed and different biochemical parameters like acetylcholinesterase (AChE), brain derived neurotropic factor (BDNF), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), superoxide dismutase (SOD) and glutathione (GSH) concentration in the hippocampus and the cerebral cortex were estimated.Results: While LPS administered animals showed significantly decreased memory retention in both MWM and Y maze, a significant reversal in all the parameters were observed following treatment with phloridzin. LPS-treated animals showed significantly decreased level of antioxidants (SOD and GSH), neurotropic factor (BDNF) and cholinergic transmission (increased AChE) and increased levels of inflammatory/oxidative markers (TNF-alpha, IL-6 and MDA) in hippocampus and cortex. These changes were alleviated after the treatment with phloridzin.Conclusions: Phloridzin may have neuroprotective role against LPS-induced neuroinflammation and memory impairment by virtue of its antioxidant, anti-inflammatory, and enhanced cholinergic signalling activity in the hippocampus and cerebral cortex.