Sophoraflavanone G prevents Streptococcus mutans surface antigen I/II-induced production of NO and PGE2 by inhibiting MAPK-mediated pathways in RAW 264.7 macrophages.
BACKGROUND
Sophora flavescens AITON (Leguminosae) is a typical traditional Korean medical herb considered to exhibit antibacterial, anti-inflammatory, and antipyretic effects, and is also used for the treatment of skin and mucosal ulcers, sores, diarrhea, gastrointestinal hemorrhage, arrhythmia, and eczema.


OBJECTIVE
This study examined the inhibitory effects of sophoraflavanone G (SF) of S. flavescens on the bacterial fibrillar protein, Antigen I/II (AgI/II)-N recombinant protein isolated from Streptococcus mutans(rAg I/II)-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). The investigation was focused on whether SF could inhibit the production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin (PG) E2 as well as the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-a, interleukin (IL)-6, nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPKs) in rAgI/II-stimulated RAW 264.7 cells using Griess reagent, Enzyme linked immunosorbent assay (ELISA), and Western blotting analysis.


RESULTS
SG significantly inhibited the production of NO and PGE2 and pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α in Ag I/II-N-stimulated RAW264.7 cells, which were mediated by the down-regulation of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. The SF inhibited the phosphorylation of IκB-α, nuclear translocation of p65, and subsequent activation of NF- κB in the rAgI/II-stimulated cells. In addition, the SF suppressed the rAgI/II-stimulated activation of ERK MAPK as well as the MAPK inhibitor significantly reduced the rAgI/II-induced production of NO and PGE2.


CONCLUSIONS
Collectively, we suggest that the SF inhibits the expression and production of inflammatory mediators by blocking the ERK MAPK mediated pathway and inhibiting the activation of NF-κB.
Department of Oral Microbiology and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, South Korea.
Su-Mi
SM
Cha
Department of Efficacy Research, Institute of Jinan red ginseng, Jinan 567-801, South Korea.
Jeong-Dan
JD
Cha
Department of Dental Technology, Daegu Health College, Daegu, South Korea.
Eun-Jin
EJ
Jang
Department of Dental Hygiene, Pohang College, Pohang, South Korea.
Gi-Ug
GU
Kim
Department of Oral Microbiology and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, South Korea. Electronic address: kyleecnu@chonbuk.ac.kr.
Kyung-Yeol
KY
Lee
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D044950:Flavanones / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D013295:Streptococcus mutans / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D016207:Cytokines; D044950:Flavanones; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C064849:vexibinol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone
Anti-inflammation; Antigen I/II of Streptococcus mutans; Inflammatory mediators; MAPKs; NF-kappa B; Sophoraflavanone G