化学
熊去氧胆酸
蛋白激酶B
MAPK/ERK通路
药理学
NF-κB
肉桂酸
消炎药
一氧化氮
体内
炎症
信号转导
促炎细胞因子
生物化学
免疫学
生物
生物技术
有机化学
作者
Xiaoxue Li,Yue Hu,Bing-xin He,Lingyu Li,Yu Tian,Yingjie Xiao,Hai Shang,Zhong‐Mei Zou
标识
DOI:10.1016/j.ejmech.2023.115785
摘要
A series of ursodeoxycholic acid (UDCA)-cinnamic acid hybrids were designed and synthesized. The anti-inflammatory activity of these derivatives was screened through evaluating their inhibitory effects of LPS-induced nitric oxide production in RAW264.7 macrophages. The preliminary structure-activity relationship was concluded. Among them, 2m showed the best inhibitory activity against NO (IC50 = 7.70 μM) with no significant toxicity. Further study revealed that 2m significantly decreased the levels of TNF-α, IL-1β, IL-6 and PGE2, down-regulated the expression of iNOS and COX-2. Preliminary mechanism study indicated that the anti-inflammatory activity of 2m was related to the inhibition of the Akt/NF-κB and MAPK signaling pathway. Furthermore, 2m reduced inflammation by a mouse model of LPS-induced inflammatory disease in vivo. In brief, our findings indicated that 2m might serve as a new lead compound for further development of anti-inflammatory agents.
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