Anti-neuroinflammatory effect of Sophoraflavanone G from Sophora alopecuroides in LPS-activated BV2 microglia by MAPK, JAK/STAT and Nrf2/HO-1 signaling pathways.
Phytomedicine
; 23(13): 1629-1637, 2016 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-27823627
ABSTRACT
BACKGROUND:
Neuroinflammation plays a vital role in Alzheimer's disease (AD) and other neurodegenerative conditions. Sophora alopecuroides is widely used in traditional Uighur's medicine for the treatment of inflammation. Sophoraflavanone G (SG), a major flavonoid found in the S. alopecuroides, has also been reported to exhibit anti-inflammatory activity both in vitro and in vivo. However, the effect of S. alopecuroides and SG on microglia-mediated neuroinflammation has not been investigated.PURPOSE:
The present study was designed to evaluate the anti-neuroinflammatory effect of S. alopecuroides and SG against lipopolysaccharide (LPS)-activated BV2 microglial cells and to explore the underlying mechanisms.METHODS:
We measured the production of pro-inflammatory mediators and cytokines, and analyzed relevant mRNA and protein expressions by qRT-PCR and Western Blot.RESULTS:
S. alopecuroides extract (SAE) and SG inhibited the LPS-induced release of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß). Additionally, SG reduced gene expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-6 and IL-1ß, and further decreased the protein expressions of iNOS and COX-2. Mechanism studies found that SG down-regulated phosphorylated mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/AKT and Janus kinase/signal transducer and activator of transcription (JAK/STAT), and up-regulated heme oxygenase-1 (HO-1) expression via nuclear translocation of nuclear factor E2-related factor 2 (Nrf2). In addition, SG inhibited the cytotoxicity of conditioned medium prepared by LPS-activated BV2 microglia to neuronal PC12 cells and improved cell viability.CONCLUSION:
S. alopecuroides and SG displayed anti-neuroinflammatory activity in LPS-activated BV2 microglia. SG was able to inhibit the neuroinflammation by MAPKs, PI3K/AKT, JAK/STAT and Nrf2/HO-1 signaling pathways and might act as a natural therapeutic agent to be further developed for the treatment of various neuroinflammatory conditions.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anti-Inflamatórios não Esteroides
/
Microglia
/
Proteínas Quinases Ativadas por Mitógeno
/
Sophora
/
Flavanonas
/
Heme Oxigenase-1
/
Proteínas de Membrana
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article