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Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro.
- Source :
- Journal of Neuroinflammation; 10/14/2020, Vol. 17 Issue 1, p1-17, 17p
- Publication Year :
- 2020
-
Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]
- Subjects :
- RECEPTOR for advanced glycation end products (RAGE)
INFLAMMATION
ADVANCED glycation end-products
ENZYME-linked immunosorbent assay
ANGER management
SALVIA miltiorrhiza
LONG-term synaptic depression
COGNITION disorders
BRAIN metabolism
BRAIN
NONSTEROIDAL anti-inflammatory agents
ANIMAL experimentation
CELLULAR signal transduction
HIPPOCAMPUS (Brain)
NEUROPROTECTIVE agents
DNA-binding proteins
INFLAMMATORY mediators
CELL lines
MICE
PHARMACODYNAMICS
CHEMICAL inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 17422094
- Volume :
- 17
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Journal of Neuroinflammation
- Publication Type :
- Academic Journal
- Accession number :
- 146431409
- Full Text :
- https://doi.org/10.1186/s12974-020-01981-4