Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro

Journal of Neuroinflammation

Hui Jin¹  Yanbing Ma¹  Yingying He¹  Xiaoqian Peng¹  John Bosco Ruganzu¹  Shengfeng Ji¹  Weina Yang¹  Bo Ding²  Chengheng Lin²  Qian Liu² 

[1] Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, 76 Yanta West Road, 710061, Xi’an, Shaanxi, China;Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, 76 Yanta West Road, 710061, Xi’an, Shaanxi, China;Medical Undergraduates of Xi’an Jiaotong University Health Science Center, 76 Yanta West Road, 710061, Xi’an, Shaanxi, China;

关键词: Alzheimer’s disease;    Tanshinone IIA;    Amyloid beta;    Neuroinflammation;    Receptor for advanced glycation end products;   

DOI  :  10.1186/s12974-020-01981-4

来源: Springer

【 摘 要 】

BackgroundGlial 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.MethodsOpen-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.ResultsTan 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.ConclusionsTaken 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.

【 授权许可】

CC BY