Oleamide suppresses inflammatory responses in LPS-induced RAW264.7 murine macrophages and alleviates paw edema in a carrageenan-induced inflammatory rat model

Oleamide compounds purified from green algae have been used for the prevention and treatment of atherosclerosis, thrombosis, arthritis, and cancer. They function through their metabolic conversion into prostaglandins, thromboxanes, and leukotrienes. However, the actual mechanism of action has not been well characterized. To investigate the underlying anti-inflammatory activity and associated mechanisms, oleamide purified from Codium fragile was studied using RAW264.7 murine macrophages and a carrageenan-induced inflammatory rat model. Our results indicate that pre-treatment of RAW264.7 cells with oleamide significantly suppressed LPS-induced nitrite production and PGE2 secretion. Oleamide inhibited LPS-induced iNOS and COX-2 mRNA and protein expression. It also inhibited the LPS-induced production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. In addition, oleamide prevented the nuclear translocation of NF-κB by suppressing the phosphorylation of the inhibitor of kappa B (IκB)-α. Oleamide also suppressed the phosphorylation of mitogen-activated protein kinases such as ERK1/2 and JNK. Furthermore, inhibition of paw swelling (%) was suppressed 2 h after the intraperitoneal injection of oleamide (20 mg/kg, body weight) in a carrageen-induced rat model. Therefore, our results suggest that oleamide can be used as a single ingredient treatment for inflammatory diseases. •Oleamide significantly suppressed LPS-induced nitrite production, and PGE2 secretion in RAW264.7 murine macrophages.•Oleamide inhibited LPS-induced pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β in RAW264.7 murine macrophages.•Oleamide inhibits the translocation of NF-κB p65 to the nucleus by inhibiting IκB-α phosphorylation.•Oleamide effectively inhibits ERK1/2 and JNK phosphorylation during LPS-induced inflammatory response.•Oleamide suppressed the carrageenan-induced paw edema thickness at 2 h after injection of carrageenan.