Sargaquinoic acid isolated fromSargassum siliquastruminhibits lipopolysaccharide-induced nitric oxide production in macrophagesviamodulation of nuclear factor-κB and c-JunN-terminal kinase pathways

Abstract

Nitric oxide (NO) is a crucial molecule in inflammatory diseases and is synthesized from L-arginine by a specific enzyme, NO synthase (NOS). The expression of inducible NOS (iNOS) is activated in macrophages by various stimuli, such as lipopolysaccharide (LPS), a wall component of gram-negative bacteria. LPS binds to toll-like receptor 4 (TLR4) on the macrophage surface and activates several downstream signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways. This study investigated whether sargaquinoic acid isolated from Sargassum siliquastrum might have anti-inflammatory activity and interfere with NO production in macrophages by disrupting LPS-induced signaling. This study was conducted in vitro using RAW264.7 murine macrophages. LPS-stimulated cells were treated with sargaquinoic acid, and the effects on NO production, iNOS expression, and involvement of the NF-κB signaling pathway were investigated by Griess assay, western blotting, and confocal microscopy. The results demonstrated that sargaquinoic acid inhibited the production of NO and the expression of the iNOS protein in LPS-stimulated RAW264.7 macrophages. Moreover, sargaquinoic acid inhibited the degradation of inhibitory-κB protein (IκB)-α and the nuclear translocation of NF-κB, a key transcription factor for the regulation of iNOS expression. Also, sargaquinoic acid influenced the phosphorylation of JNK1/2 MAPK, except ERK1/2 and p38 MAPKs, stimulated by LPS. These results suggest that sargaquinoic acid specifically prevents NO production in macrophages via the blockade of NF-κB activation and may thus have therapeutic applications in various inflammatory diseases.

Panax Notoginseng flower saponins (PNFS) inhibit LPS-stimulated NO overproduction and iNOS gene overexpression via the suppression of TLR4-mediated MAPK/NF-kappa B signaling pathways in RAW264.7 macrophages

“…TLR4 triggers activation of MAPK/NF-kappa B signaling pathways to induce iNOS gene overexpression [ 29 ], and the TLR4-mediated signaling pathway also rapidly activates the PI3K/Akt signaling pathway to negatively regulate iNOS gene expression [ 23 , 30 ]. PNFS had an obvious suppressive effect on LPS-activated TLR4 mRNA overexpression, suggesting that PNFS could inhibit the overproduction of NO and the overexpression of iNOS by blocking the TLR4 signaling pathway.…”

The role of TLRs in cervical cancer with HPV infection: a review

“…TLR4 activates signal transduction by the MyD88-dependent and MyD88-independent pathways, which in turn modulate inducible nitric oxygen synthase (iNOS) through tumor necrosis factor receptor-associated factor 6 (TRAF6), MAPK, NF-κB and other key genes. 43 Rahkola et al 44 found that patients with HR-HPV infection have higher nitric oxide (NO) in the cervical canal than do HPV-negative patients, indicating that the release of NO is closely related to HPV infection. The expression of iNOS in prostate cancer, head and neck squamous cell carcinoma, gynecological tumors, 45 breast cancer, and lung cancer tissues was different from that of normal tissue.…”

Sargachromenol from Sargassum micracanthum Inhibits the Lipopolysaccharide‐Induced Production of Inflammatory Mediators in RAW 264.7 Macrophages

“…During our ongoing screening program designed to identify the anti-inflammatory potential of natural compounds, we isolated fucosterol, sargaquinoic acid, and sargachromenol from S. micracanthum by using activity-directed fractionation and characterized their structures using spectroscopy ( 1 H and 13 NMR, IR, and MS) as described previously [15]. However, the biological activities or modes of action of these compounds have not been reported previously, although another Korean group recently reported that sargaquinoic acid has anti-inflammatory activity [18]. Therefore, the present study investigated whether sargachromenol inhibited LPS-induced production of NO and PGE 2 , or the expression of iNOS and COX-2 proteins, through the inhibition of I κ B- α in macrophages.…”