Aqueous extract of Codium fragile suppressed inflammatory responses in lipopolysaccharide-stimulated RAW264.7 cells and carrageenan-induced rats

Codium fragile (Suringar) Hariot has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria and has been shown to have various biological effects. In this study, we evaluated the anti-inflammatory effects of aqueous extract of C. fragile (AECF) using in vitro and in vivo models. Nitric oxide (NO), prostaglandin E-2 (PGE(2)), inflammatory-related mRNAs, and proteins were determined using the Griess assay, enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and western blotting, respectively. Our results indicate that pretreatment of cells with AECF (50, 100 and 200 mg/mL) significantly inhibited LPS-induced secretion of NO and PGE2 in RAW264.7 cells without cytotoxicity. We also found that AECF (100 and 200 mg/mL) inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 expression in a dose-dependent manner. Additionally, pretreatment of cells with AECF (100 and 200 mg/mL) inhibited LPS-induced production of inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6. It also prevented the nuclear translocation of nuclear factor (NF)-kappa B by suppressing the phosphorylation and degradation of inhibitor of NF-kappa B (I kappa B)-alpha. Furthermore, AECF (100 and 200 mg/mL) inhibited the phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK) 1/2, c-Jun Nterminal kinase (JNK), and p38. In addition, orally administered 50, 100, and 200 mg/kg body weight of AECF dose-dependently suppressed carrageenan-induced rat paw edema thickness by 6%, 31%, and 50% respectively, after 4 h. Furthermore, the anti-inflammatory effect was comparable to that observed in animals treated with the standard drug diclofenac sodium (56%) in vivo. Collectively, our results suggest that AECF exerts potential anti-inflammatory effects by suppressing NF-kB activation and MAPKs pathways in vitro, as well as inhibiting carrageenan-induced rat paw edema thickness in vivo. These findings indicate that AECF could be further developed as an anti-inflammatory drug. (C) 2017 Elsevier Masson SAS. All rights reserved.