Design, synthesis and evaluation of anti-inflammatory effect of novel berberine derivatives on IL-6/STAT signaling pathway
10.16438/j.0513-4870.2017-0835
- VernacularTitle:基于阻断IL-6/STAT信号通路的全新小檗碱衍生物的设计、合成及其抗炎作用评价
- Author:
Qing-xuan ZENG
1
;
Na ZHANG
1
;
Hong-bin DENG
1
;
Dan-qing SONG
1
;
Jian-dong JIANG
1
;
Yan-xiang WANG
1
Author Information
1. Institute of Medicinal Biotechnology, China Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
berberine;
atherosclerosis;
structure-activity relationship;
IL-6;
STAT-1/3
- From:
Acta Pharmaceutica Sinica
2017;52(12):1895-1902
- CountryChina
- Language:Chinese
-
Abstract:
Interleukin-6 (IL-6)/signal transducers and activators of transcription (STAT) signaling pathway is closely related to the development and progression of atherosclerosis (AS). Taking Chinese natural product berberine (BBR) as the leading compound, a series of novel BBR analogues defined on different types of substituents on position 3 or/and 9 were designed, synthesized and evaluated for their inhibitory activities on phosphorylation of STAT-1 and STAT-3 induced by IL-6. The structure-activity relationship indicated that introduction of rigid fragment on position 3 or 9 was beneficial for enhancing their activities. Among them, compounds 2b and 9 exhibited the most satisfactory potency. The study revealed that the compounds 2b and 9 exhibit anti-inflammatory potencies via activating AMPK, and down-regulation of phosphorylation of STAT1 and STAT3 induced by IL-6 in HUVEC cells. These results suggest that BBR derivatives may inhibit the inflammatory response mediated by the IL-6/STAT signaling pathway through regulation of AMPK, which provides useful insight into the development of BBR derivatives for treatment of atherosclerosis.
