Poster Presenter

The Basic Medical Study of Kampo Medicines on the Treatment of Periodontal Disease
Pao-Li Wang, Toshiaki Ara
Japan

Purpose: Periodontal disease is known to increase the risks of various disorders such as aspiration pneumonia, infective endocarditis, arteriosclerosis, diabetes, low birth weight infant and tumor. In periodontal disease, gingival fibroblasts, monocytes and macrophages produce prostaglandin E2 (PGE2) and inflammatory cytokines such as interleukin (IL)-6 and IL-8 by the stimulation with extracellular substances of periodontopathic bacteria, leading to inflammation of periodontal tissues. For the treatment of periodontal disease, the elimination of biofilm and dental calculus is needed. In severe inflammation, however, anti-inflammatory drugs are often used.

We have reported that a kampo medicine, shosaikoto (TJ-9), decreases LPS-induced PGE2 production by gingival fibroblasts (Ara T, et al. Biol Pharm Bull 31: 1141-1144, 2008). In this study, we examined the anti-inflammatory effect of other kampo medicines (orento, TJ-120; orengedokuto, TJ-15; hangeshashinto, TJ-14; hainosankyuto; TJ-122; hochuekkito, TJ-41), which are clinically used for the treatment of periodontal disease, by the measurement of PGE2, IL-6 and IL-8 produced by gingival fibroblasts.

Materials and Methods: The powder of each kampo medicine was suspended in D-MEM supplemented with 10% FCS and rotated at 4°C overnight. Then, the suspensions were centrifuged and filtrated through 0.45 mm-pore membrane. Gingival fibroblasts were prepared and cultured from explants of human normal gingival tissues.
Gingival fibroblasts were stimulated with 10 ng/ml of LPS from Porphyromonas gingivalis and various concentration of kampo medicines for 24 h. The levels of PGE2, IL-6 and IL-8 were measured by ELISA.

Results: (1) Orento (TJ-120), orengedokuto (TJ-15) and hangeshashinto (TJ-14) were dose-dependently decreased LPS-induced PGE2 productions. In contrast, they showed no effect on LPS-induced IL-6 and IL-8 productions. (2) Hainosankyuto (TJ-122) increased LPS-induced PGE2 production in a low concentration but dec reased in a high concentration. In contrast, hainosankyuto increased LPS-induced IL-6 and IL-8 productions. (3) Hochuekkito (TJ-41) increased LPS-induced PGE2, IL-6 and IL-8 productions. (4) All kampo medicines used in this study have no effect on basal level of PGE2.

Discussion: Orento, orengedokuto and hangeshashinto are used for the treatment of inflammatory disorders. Because these kampo medicines also decrease LPS-induced PGE2 productions by gingival fibroblasts, it is suggested that they show anti-inflammatory effect in periodontal tissues.
Hainosankyuto is used for the treatment of purulence accompanied by redness, swelling and pain. Hochuekkito is used for infirmity. Because these two kampo medicines increase the production of inflammatory cytokines, it is suggested that immune cells migrate into inflammatory region and phagocytose periodontopathic bacteria.