Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro
| Autor: | John Bosco Ruganzu, Xiaoqian Peng, Bo Ding, Yanbing Ma, Shengfeng Ji, Chengheng Lin, Yingying He, Qian Liu, Hui Jin, Wei-Na Yang |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Amyloid beta Immunology Mice Transgenic Tanshinone IIA Pharmacology Salvia miltiorrhiza Neuroprotection lcsh:RC346-429 RAGE (receptor) Mice Cellular and Molecular Neuroscience Neuroinflammation In vivo Cell Line Tumor mental disorders medicine Animals Humans Cognitive decline Maze Learning lcsh:Neurology. Diseases of the nervous system biology Chemistry Research General Neuroscience Anti-Inflammatory Agents Non-Steroidal NF-kappa B Neurotoxicity Brain medicine.disease Neuroprotective Agents Neurology Abietanes biology.protein Inflammation Mediators Receptor for advanced glycation end products Alzheimer’s disease Signal Transduction |
| Zdroj: | Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-17 (2020) Journal of Neuroinflammation |
| ISSN: | 1742-2094 |
| Popis: | 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 herbalSalvia miltiorrhizaBunge, 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. |
| Databáze: | OpenAIRE |
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