Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro.
Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro.
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DOI：
10.1186/s12974-020-01981-4
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发表时间：
2020-10-14
影响因子：
9.3
通讯作者：
Yang W
中科院分区：
文献类型：
--
作者：
Ding B;Lin C;Liu Q;He Y;Ruganzu JB;Jin H;Peng X;Ji S;Ma Y;Yang W
胶质细胞活化和神经炎症在阿尔茨海默病（AD）的发病和发展中起着至关重要的作用。晚期糖基化终末产物受体（receptor for advanced glycation end products，ERK）介导的信号通路与β淀粉样蛋白（amyloid beta，Aβ）诱导的神经炎症有关。本研究旨在探讨丹参酮IIA（tanshinone IIA，tan IIA）对Aβ诱导的神经炎症、认知障碍和神经毒性的保护作用及其机制。采用旷场实验、Y迷宫实验和Morris水迷宫实验评价APP/PS 1小鼠的认知功能。通过免疫组织化学、免疫荧光、硫磺素S（Th-S）染色、酶联免疫吸附试验（ELISA）、实时定量逆转录聚合酶链反应（qRT-PCR）和蛋白质印迹法，研究Aβ沉积、突触和神经元丢失、小胶质细胞和星形胶质细胞活化、RAGE依赖性信号传导、以及APP/PS 1小鼠和培养的BV 2和U87细胞中促炎细胞因子的产生。Tan IIA治疗预防APP/PS1小鼠的空间学习和记忆缺陷。此外，tan IIA减弱了APP/PS1小鼠皮质和海马中的Aβ蓄积、突触相关蛋白（Syn和PSD-95）和神经元丢失，以及斑块周围小胶质细胞增生和星形细胞增生。此外，tan IIA显著抑制APP/PS1小鼠和培养的BV 2和U87细胞中的NF-κB/NF-κB信号通路和促炎细胞因子（TNF-α、IL-6和IL-1β）的产生。综上所述，本研究结果表明，tan IIA在体内外部分通过抑制NF-κB信号通路改善认知功能减退和神经炎症。因此，tan IIA可能是一种有前途的治疗药物，用于阻止和预防AD进展。
Glial activation and neuroinflammation play a crucial role in the pathogenesis and development of Alzheimer’s disease (AD). The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to amyloid beta (Aβ)-induced neuroinflammation. This study aimed to investigate the neuroprotective effects of tanshinone IIA (tan IIA), a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza Bunge, against Aβ-induced neuroinflammation, cognitive impairment, and neurotoxicity as well as the underlying mechanisms in vivo and in vitro. Open-field test, Y-maze test, and Morris water maze test were conducted to assess the cognitive function in APP/PS1 mice. Immunohistochemistry, immunofluorescence, thioflavin S (Th-S) staining, enzyme-linked immunosorbent assay (ELISA), real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blotting were performed to explore Aβ deposition, synaptic and neuronal loss, microglial and astrocytic activation, RAGE-dependent signaling, and the production of pro-inflammatory cytokines in APP/PS1 mice and cultured BV2 and U87 cells. Tan IIA treatment prevented spatial learning and memory deficits in APP/PS1 mice. Additionally, tan IIA attenuated Aβ accumulation, synapse-associated proteins (Syn and PSD-95) and neuronal loss, as well as peri-plaque microgliosis and astrocytosis in the cortex and hippocampus of APP/PS1 mice. Furthermore, tan IIA significantly suppressed RAGE/nuclear factor-κB (NF-κB) signaling pathway and the production of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in APP/PS1 mice and cultured BV2 and U87 cells. Taken together, the present results indicated that tan IIA improves cognitive decline and neuroinflammation partly via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro. Thus, tan IIA might be a promising therapeutic drug for halting and preventing AD progression.
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