Hangeshashinto Inhibits Porphyromonas gingivalis Pathogen-Associated Molecular Patterns-Mediated IL-6 and IL-8 Production through Toll-Like Receptors in CAL27 Cells

While previous reports have established the anti-inflammatory effects of hangeshashinto, the intracellular signal transduction pathways involved have yet to be elucidated. We aim to employ an experimental system using oral cancer cells to assess the impact of hangeshashinto on intracellular signal transduction pathways in response to stimulation by Porphyromonas gingivalis pathogen-associated molecular patterns (PAMP). Hangeshashinto demonstrated the ability to inhibit the production of interleukin (IL)-6 and IL-8 induced by P. gingivalis PAMP. Furthermore, hangeshashinto suppressed the activation of the IL-6 promoter stimulated by PAMP. Hangeshashinto, like Toll-like receptor (TLR) signaling inhibitors (resatorvid and C29) and an immunosuppressant (dexamethasone), exhibited the ability to suppress TLR-mediated activation of the transcription factor nuclear factor-κB (NF-κB) in response to PAMP stimulation. This study suggests that the anti-inflammatory effects of hangeshashinto may be attributed to the inhibition of TLR signal transduction pathways including NF-κB activation, thereby suppressing NF-κB-dependent gene expression.