5, 7, 2', 4', 5'-Pentamethoxyflavanone regulates M1/M2 macrophage phenotype and protects the septic mice.
10.1016/S1875-5364(19)30042-1
- Author:
Li-Li FENG
1
;
Li-Sha XU
1
;
Meng-Meng GUO
1
;
Wei HUANG
1
;
Jia-Zhen ZHU
1
;
Ling-Dong KONG
1
;
Xu-Dong WU
2
;
Qiang XU
3
,
4
Author Information
1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
2. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China. Electronic address: xudongwu@nju.edu.cn.
3. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China. Electronic address: molpharm@
4. com.
- Publication Type:Journal Article
- Keywords:
5, 7, 2’, 4’, 5’-Pentamethoxyflavanone (Pen.);
Anti-inflammation;
Macrophage polarization;
NFκB;
Sepsis
- From:
Chinese Journal of Natural Medicines (English Ed.)
2019;17(5):363-371
- CountryChina
- Language:English
-
Abstract:
Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2', 4', 5'-pentamethoxyflavanone (abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mRNA and protein level of proinflammatory cytokines, IL-1β, IL-6, TNF-α and iNOS, which was characteristic expressed on M1 polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.
