Agrimonolide from Agrimonia pilosa suppresses inflammatory responses through down-regulation of COX-2/iNOS and inactivation of NF-κB in lipopolysaccharide-stimulated macrophages.
BACKGROUND
Agrimonolide from Agrimonia pilosa showed a strong anti-inflammatory activity, and the present study aims to reveal potential mechanisms on molecular level explaining its anti-inflammatory effect.


OBJECTIVE
To investigate the mechanism of anti-inflammatory activity of agrimonolide.


METHODS
Anti-inflammatory activity of agrimonolide in cells was applied.


METHODS
Anti-inflammatory activity of agrimonolide isolated from Agrimonia pilosa was evaluated using lipopolysaccharide (LPS) stimulated RAW 264.7 cell models. The productions of IL-1β, IL-6, TNF-α and NO were determined by ELISA and nitrite analysis, respectively. The expressions of iNOS and COX-2 were measured by western blotting and RT-PCR analysis.


RESULTS
The pre-treatment with agrimonolide significantly reduced the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), as well as attenuated the expression of iNOS and COX-2 in LPS-stimulated macrophages. Furthermore, agrimonolide inhibited the activation of JNK and p38 MAPKs and decreased the activation of JAK-STAT and NF-κB in LPS-stimulated macrophages.


CONCLUSIONS
The present study suggested that agrimonolide exerted anti- inflammatory activity, at least in part, via suppressing LPS-induced activation of JAK-STATs and p38 MAPKs signaling pathway.
College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China.
Lei
L
Chen
College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China.
Hui
H
Teng
College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China. Electronic address: fangting930@163.com.
Ting
T
Fang
Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, Macau. Electronic address: jianboxiao@yahoo.com.
Jianbo
J
Xiao
D031981:Agrimonia / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049934:Isocoumarins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D000067996:RAW 264.7 Cells
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D004791:Enzyme Inhibitors; D049934:Isocoumarins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C036057:agrimonolide; D052247:Nitric Oxide Synthase Type II
Agrimonolide; Anti-inflammation; Macrophages; Mechanism