The anti-HSV-1 effect of quercetin is dependent on the suppression of TLR-3 in Raw 264.7 cells

• Published in: Archives of pharmacal research Vol. 40; no. 5; pp. 623 - 630
• Main Authors: Lee, Seulki, Lee, Hwan Hee, Shin, Yu Su, Kang, Hyojeung, Cho, Hyosun
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.05.2017; 대한약학회
• Subjects: Animals; anti-inflammatory activity; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Asia; Cells, Cultured; Cercopithecus aethiops; Dose-Response Relationship, Drug; genes; Glycyrrhiza uralensis; herpes simplex; Herpesvirus 1, Human - drug effects; Herpesvirus 1, Human - genetics; Human alphaherpesvirus 1; inflammation; Medicine; Mice; Microbial Sensitivity Tests; Molecular Structure; pathogenicity; Pharmacology/Toxicology; Pharmacy; quantitative polymerase chain reaction; quercetin; Quercetin - chemical synthesis; Quercetin - chemistry; Quercetin - pharmacology; RAW 264.7 Cells; Research Article; Structure-Activity Relationship; Toll-Like Receptor 3 - antagonists & inhibitors; Toll-Like Receptor 3 - metabolism; traditional medicine; transcription factor NF-kappa B; tumor necrosis factor-alpha; Vero Cells; Western blotting; 약학; Asia; HSV-1; TLR-3; Raw 264.7 cells; Anti-inflammation; Quercetin
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-017-0898-x

Quercetin is a major component of the plant Glycyrrhiza uralensis , which is largely used as a traditional medicine in Asia. Quercetin has been reported to have several biological activities, which include anti-viral and anti-inflammatory effects. We explored the molecular mechanism linking anti-viral and anti-inflammatory activities using an in vitro herpes simplex virus-1 (HSV-1) infection model. Raw 264.7 cells were infected with HSV-1 in the presence or absence of different concentrations of quercetin and infected cell lysates were harvested 24 h later. HSV plaque reduction assays, western blotting (HSV-1gD, HSV-1 ICP0, TLR-2, 3, 9, NF-κB, IRF3), and real time PCR (HSV-1ICP0, HSV-1UL13, HSV-1UL52) were performed to elucidate the mechanism responsible for the anti-HSV-1 effect of quercetin. In addition, TNF-α level was measured. Quercetin significantly lowered HSV infectivity in Raw 264.7 cells and inhibited the expressions of HSV proteins (gD, ICP0) and genes (ICP0, UL13, UL52). Interestingly, quercetin specifically suppressed the expression of TLR-3, and this led to the inhibitions of inflammatory transcriptional factors (NF-κB and IRF3). These findings suggest that the anti-HSV-1 effects of quercetin are related to the suppression of TLR-3 dependent inflammatory responses in Raw 264.7 cells.