School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Phytomedicine. 2023 Apr;112:154695. doi: 10.1016/j.phymed.2023.154695. Epub 2023 Feb 7.
Shi chang pu (Acorus tatarinowii Schott) is a herbal used in the treatment of Alzheimer's disease (AD) in China. The essential oil of Shi chang pu (SCP-oil) is the main active component. However, its effects on the neuroinflammation of AD have not been well studied.
Neuroinflammation mediated by the NLRP3 inflammasome plays a crucial role in AD. This study was designed to evaluate the effect of SCP-oil on cognitive impairment of App/PSEN1/MAPT triple transgenic (3 × Tg-AD) mice model and investigate the mechanism underlying its anti-inflammation effects.
Thirty-two 3 × Tg-AD mice at 12 months and 8 wild-type B6 mice were used for this experiment. The 3 × Tg-AD mice were administered with SCP-oil or donepezil hydrochloride for 8 weeks. Morris water maze test and step-down test were used to evaluate the cognitive ability of mice. The pathological changes, neuroinflammation, and the NLRP3 inflammasome related-protein of AD mice were detected by histomorphological examination, TUNEL staining, immunofluorescence, immunohistochemistry, qRT-PCR, Elisa, and western blot assays.
SCP-oil treatment attenuated cognitive dysfunction of 3 × Tg-AD mice. Moreover, SCP-oil also ameliorated characteristics pathological of AD, such as pathological changes damage, deposition of Aβ, phosphorylation of Tau, and neuronal loss. Additionally, SCP-oil treatment alleviated the neuroinflammation and inhibited phosphorylation of IKKβ, NF-κB, and NLRP3 inflammasome related-protein NLRP3, ASC, Caspase-1, cleaved-Caspase-1, and GSDMD-N in the hippocampus of 3 × Tg-AD mice.
Overall, SCP-oil contributed to neuroprotection in 3 × Tg-AD mice by reduced activation of NLRP3 inflammasome by inhibiting the NF-κB signaling pathway.
石菖蒲（Acorus tatarinowii Schott）是中国用于治疗阿尔茨海默病（AD）的草药。石菖蒲精油（SCP-油）是其主要活性成分。然而，其对 AD 的神经炎症的影响尚未得到很好的研究。
NLRP3 炎性小体介导的神经炎症在 AD 中起着至关重要的作用。本研究旨在评估 SCP-油对 App/PSEN1/MAPT 三转基因（3×Tg-AD）小鼠模型认知障碍的影响，并探讨其抗炎作用的机制。
本实验使用了 32 只 12 月龄的 3×Tg-AD 小鼠和 8 只野生型 B6 小鼠。将 3×Tg-AD 小鼠给予 SCP-油或多奈哌齐盐酸盐治疗 8 周。Morris 水迷宫试验和跳台试验用于评估小鼠的认知能力。通过组织形态学检查、TUNEL 染色、免疫荧光、免疫组织化学、qRT-PCR、ELISA 和 Western blot 检测 AD 小鼠的病理变化、神经炎症和 NLRP3 炎性小体相关蛋白。
SCP-油治疗可改善 3×Tg-AD 小鼠的认知功能障碍。此外，SCP-油还改善了 AD 的特征性病理变化，如病理损伤、Aβ沉积、Tau 磷酸化和神经元丢失。此外，SCP-油治疗可减轻神经炎症，并抑制 IKKβ、NF-κB 和 NLRP3 炎性小体相关蛋白 NLRP3、ASC、Caspase-1、cleaved-Caspase-1 和 GSDMD-N 在 3×Tg-AD 小鼠海马中的磷酸化。
总的来说，SCP-油通过抑制 NF-κB 信号通路减少 NLRP3 炎性小体的激活，对 3×Tg-AD 小鼠发挥神经保护作用。
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