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Exocarpium Citri Grandis (ECG) is used as an antitussive and anti-inflammatory agent in traditional Chinese medicine. However, the mechanism of its anti-inflammatory effect remains unknown. In this study, flavonoids of ECG (FECG) were extracted to investigate the anti-inflammatory effect using a RAW264.7 macrophage model. The results suggested that FECG could remarkably inhibit the production of nitric oxide (NO). Meanwhile, FECG decreased the mRNA and protein expression of inflammatory cytokines including tumour necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), while showed an opposite effect on interleukin-10 (IL-10). Furthermore, FECG suppressed the phosphorylation of p38 (p38 kinase), JNK (c-Jun N-terminal kinase), ERK (extracellular signal-regulated kinase) and NF-κB. Taken together, our results indicated that FECG might regulate the activation of MAPK and NF-κB signalling pathways to exert anti-inflammatory effects. This study provides some insights into the mechanism underlying the anti-inflammatory activity of ECG, which may facilitate a better application of ECG. [ABSTRACT FROM AUTHOR]