Inhibitory effect and mechanism of licochalcone A on NLRP3 inflammasome
10.16438/j.0513-4870.2018-0713
- VernacularTitle:甘草查尔酮A对NLRP3炎症小体的调控作用及机制初探
- Author:
Shu-bin FU
1
;
Guang XU
2
;
Yuan GAO
3
;
Zhi-lei WANG
4
;
Nan QIN
1
;
Hui-min LIU
2
;
Zhao-fang BAI
2
;
Xiao-he XIAO
2
Author Information
1. School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
2. China Military Institute of Chinese Medicine, 302 Military Hospital of China, Beijing 100039, China
3. School of Pharmacy, Beijing University of Traditional Chinese Medicine, Beijing 100029, China
4. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
licochalcone A;
NLRP3 inflammasome;
caspase-1;
IL-1β
- From:
Acta Pharmaceutica Sinica
2018;53(12):2050-2056
- CountryChina
- Language:Chinese
-
Abstract:
Lipopolysaccharide (LPS)-induced bone marrow-derived macrophages (BMDMs), treated with licochalcone A (LCA) and retreated with inflammasome inducers respectively (ATP and nigericin), were used to construct the inflammasome model of NLRP3 (NOD-like receptor family, pyrin domain containing 3), to investigate the inhibitory effect and the molecular mechanism of LCA on the activity of NLRP3 inflammasome. The secretion of mature interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and caspase-1 in the supernatants were analyzed by ELISA and the Caspase-Glo® 1 Inflammasome Assay. Supernatants and cell lysates were analyzed for the expression of pro-caspase-1, pro-IL-1β, ASC, NLRP3, IL-1β, caspase-1 by immunoblotting. The study shows that LCA inhibited the activity of caspase-1 and the secretion of IL-1β, and suppressed the activity of NLRP3 inflammasome. There was also slight inhibition of NLRC4 inflammasome induced by Lfn-Flic, but no effect on poly(dA:dT)-induced the absent in melanoma 2 (AIM2) inflammasome. Western blot showed that LCA had no effect on the protein expression of NLRP3 and pro-IL-1β, which was mediated by NF-κB pathway. In summary, LCA can inhibit the cleavage of pro-caspase-1 and suppress the secretion of IL-1β to reduce the inflammation response. The study was carried out under the approval of the Scientific Investigation Board of 302 Hospital of PLA.
