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Published on: March 28, 2025
Hangeshashinto Inhibits Porphyromonas gingivalis Pathogen-Associated Molecular Patterns-Mediated IL-6 and IL-8
Hourei Oh1, Yoshimasa Makita2, Kazuya Masuno1
1Center of Innovation in Dental Education, Osaka Dental University, Osaka 573-1121, Japan.
Abstract:
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.
Insights
Hangeshashinto, a traditional medicine, inhibits inflammatory responses by blocking key signaling pathways like nuclear factor-kappaB (NF-κB) activation. This study clarifies its anti-inflammatory mechanism in oral cancer cells against bacterial stimulation.
Area of Science:
- Immunology
- Pharmacology
- Oral Biology
Background:
- Hangeshashinto is known for anti-inflammatory effects, but its intracellular mechanisms are unclear.
- Oral bacteria like Porphyromonas gingivalis can trigger inflammatory responses via pathogen-associated molecular patterns (PAMP).
Purpose of the Study:
- To investigate the impact of hangeshashinto on intracellular signal transduction pathways in oral cancer cells stimulated by P. gingivalis PAMP.
- To elucidate the molecular mechanisms underlying hangeshashinto's anti-inflammatory properties.
Main Methods:
- Oral cancer cells were stimulated with P. gingivalis PAMP.
- The effects of hangeshashinto on cytokine production (IL-6, IL-8) and promoter activation were measured.
- Activation of Toll-like receptor (TLR) signaling and nuclear factor-kappaB (NF-κB) pathways were assessed.
Main Results:
- Hangeshashinto inhibited P. gingivalis PAMP-induced production of interleukin-6 (IL-6) and IL-8.
- It suppressed IL-6 promoter activation and TLR-mediated NF-κB activation.
- These effects were comparable to known TLR inhibitors and an immunosuppressant.
Conclusions:
- Hangeshashinto exerts anti-inflammatory effects by inhibiting TLR signal transduction pathways.
- Suppression of NF-κB activation is a key mechanism, leading to reduced NF-κB-dependent gene expression.
- This study provides molecular insights into hangeshashinto's anti-inflammatory action in the context of oral inflammation.
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