Elucidation of carcinogenesis signaling mechanism by chronic periodontitis and development of drug discovery derived from Kampo medicine

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K09929
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57080:Social dentistry-related
• Research Institution: Osaka Dental University
• Principal Investigator: OH Hourei 大阪歯科大学, 歯学部, 教授 (20213613)
• Co-Investigator(Kenkyū-buntansha): 今村 泰弘 松本歯科大学, 歯学部, 講師 (00339136)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 漢方薬 / 歯周病 / 慢性炎症 / 抗炎症作用 / 発ガン抑制

Outline of Final Research Achievements

In oral squamous cell carcinoma cell line CAL27, orento significantly inhibited periodontopathogenic bacterium Porphyromonas gingivalis lipopolysaccharide (LPS) and lipoproteins (PAMP)-stimulated production of interleukin (IL)-6. This finding indicates that orento may suppress the function and activation of factors involved in TLR signaling, thereby suppressing NF-kB-dependent expression of various genes. Orento suppressed IL-1 receptor-associated kinase (IRAK4), IRAK1, and c-Jun N-terminal kinase (JNK) phosphorylation in PAMP-stimulated CAL27 cells. This result indicates that orento is involved in the initiation of TLR signaling by PAMP and suppresses the downstream signaling pathways of myeloid differentiation primary response gene 88 (MyD88) such as mitogen-activated protein kinase (MAPK) and NF-kB cascades. These findings suggest that orento has an inhibitory effect on the production of inflammatory cytokines.

Free Research Field

漢方医学

Academic Significance and Societal Importance of the Research Achievements

学術的意義は歯周病関連細菌とがん細胞とのIL-6 の発現を分子生物学的にTLRシグナル伝達経路で解明でき、その経路を漢方薬が遮断したことである。一方、社会的意義としてはまず歯周病は細菌感染による慢性疾患である。つまり慢性疾患はがん発症に関与することから、抗炎症作用のある漢方薬は「未病を防ぐ」発想になり、予防医学に発展すると考えることができる。従って、患者様のがんによる痛みや治療費の負担は軽減する。