Sparassis crispa exerts anti-inflammatory activity via suppression of TLR-mediated NF-κB and MAPK signaling pathways in LPS-induced RAW264.7 macrophage cells. (1st March 2019)

• Record Type: Journal Article
• Authors: Han, Jang Mi; Lee, Eun Kyeong; Gong, So Youn; Sohng, Jae Kyung; Kang, Yue Jai; Jung, Hye Jin
• Is Part Of: Journal of ethnopharmacology. Volume 231(2019)
• Page Start: 10
• Page End: 18
• Publication Date: 2019-03-01
• Subjects: LPS lipopolysaccharide -- HPLC high-performance liquid chromatography -- ELISA enzyme-linked immunosorbent assay -- NO nitric oxide -- PGE2 prostaglandin E2 -- TNF-α tumor necrosis factor-α -- IL-6 interleukin-6 -- iNOS inducible nitric oxide synthase -- COX-2 cyclooxygenase-2 -- NF-κB nuclear factor-kappa B -- MAPK mitogen-activated protein kinase -- IκBα inhibitor of κB alpha -- TAK1 transforming growth factor beta-activated kinase 1 -- TLR toll-like receptor -- ROS reactive oxygen species -- IKK IκB kinase -- ERK extracellular signal-regulated kinase -- JNK c-Jun N-terminal kinase -- AP-1 activator protein-1 -- ATF2 activating transcription factor 2 -- MEF myocyte enhancer factor -- TIR toll-interleukin-1 receptor; Sparassis crispa -- Anti-inflammation -- TLR -- NF-κB -- MAPK; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2018.11.003
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacology relevance: Sparassis crispa, also known as cauliflower mushroom, has been used historically in traditional Asian medicine. It possesses various biological activities, such as immunopotentiation, anti-diabetes, anti-cancer, and anti-inflammatory effects. Recently, we isolated the non-aqueous fraction from methanol extract of S. crispa (SCF4) by using water-organic solvent mixtures and high-performance liquid chromatography (HPLC). In the present study, we identified the anti-inflammatory activity and action mechanism of SCF4 in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells. Materials and methods: The chloroform layer isolated from S. crispa methanol extract was separated into seven fractions using preparative HPLC. The fractions were then applied to NO assay to identify the fraction with the best anti-inflammatory activity. The inflammation inhibitory effect and underlying mechanism of SCF4 in LPS-stimulated RAW264.7 cells were assessed using WST-1 assay, enzyme-linked immunosorbent assay (ELISA), ROS assay, and Western blot analysis. Results: SCF4 significantly suppressed LPS-induced production of pro-inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2 ), and pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)− 6, and IL-1β, without cytotoxicity. In addition, SCF4 downregulated not only the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), but also the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) stimulated by LPS. SCF4 also blocked the nuclear translocation of NF-κB via reduction of inhibitor of κB alpha (IκBα) degradation. Furthermore, SCF4 inhibited the phosphorylation of transforming growth factor beta-activated kinase 1 (TAK1), an important upstream factor of NF-κB and MAPK signaling mediated through toll-like receptor (TLR). Conclusions: These findings demonstrate for the first time the correlation between the anti-inflammatory activity of SCF4 and TLR-mediated NF-κB and MAPK signaling pathways in LPS-stimulated RAW264.7 macrophage cells, suggesting that the non-aqueous extract of S. crispa could be applied as a promising natural product for the prevention and treatment of inflammatory diseases. Graphical abstract: