nhibitory effect and mechanism of deoxyschizandrin on NLRP3 inflammasome
10.16438/j.0513-4870.2016-0784
- VernacularTitle:五味子甲素对NLRP3炎性小体活性的抑制作用及机制初步研究
- Author:
He-rong CUI
1
;
Peng-yan LI
1
;
Yu-meng LI
2
;
Rui-lin WANG
3
;
Juan-juan HE
1
;
Xiu-xiu SANG
4
;
Guang-ming CAI
1
;
Ming NIU
1
;
Jia-bo WANG
1
;
Zhao-fang BAI
1
;
Xiao-he XIAO
3
Author Information
1. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China
2. First Hospital of Qinhuangdao, Qinhuangdao 066000, China
3. Integrative Medicine Center, 302 Military Hospital, Beijing 100039, China
4. Chengde Medical University, Chengde 067000, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
deoxyschizandrin;
NLRP3 inflammasome;
inflammatory response;
caspase-1
- From:
Acta Pharmaceutica Sinica
2017;52(1):80-85
- CountryChina
- Language:Chinese
-
Abstract:
This study was conducted to investigate the inhibitory effect and the molecular mechanism of deoxyschizandrin on the activity of NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome. Bone marrow-derived macrophages were used to study the effects of deoxyschizandrin on inflammasome activation using inflammasome inducers (ATP and nigericin). Cytotoxic effect was evaluated with CCK-8. The expression of IL-1β, caspase-1 in the supernatant and the expression of pro-caspase-1, pro-IL-1 β, ASC, NLRP3 in cell was detected by Western blot for the inhibitory effect of deoxyschizandrin (25, 50, 100 and 200 μmol·L-1) on the activity of NLRP3 inflammasome. Immunofluorescence was applied to investigate NF-κB (p65) transportation to the nucleus. The results of CCK-8 showed that the optimum concentration of deoxyschizandrin was 6.25-400 μmol·L-1. Deoxyschizandrin (25, 50, 100, and 200 μmol·L-1) could inhibit the activation of NLRP3 inflammasome caused by nigericin and ATP, and inhibit the secretion of IL-1 β, which was associated with inhibiting the cleavage of pro-caspase-1. The results of immunofluorescence and Western blot also suggest that the inhibitory activity of deoxyschizandrin on NLRP3 inflammasome was not dependent on NF-κB pathway and protein expression of NLRP3, ASC, pro-caspase-1 and pro-IL-1 β mediated by NF-κB. Our results confirmed that deoxyschizandrin could suppress the cleavage of pro-caspase-1 and inhibit the activity of NLRP3 inflammasome at 25-200 μmol·L-1 to reduce the inflammation response.
