Comparison between hangeshashinto and dexamethasone for IL-1α and β-defensin 1 production by human oral keratinocytes

• Published in: Journal of oral biosciences Vol. 66; no. 1; pp. 188 - 195
• Main Authors: Hato, Hiroyuki, Kaneko, Atsushi, Maeda, Chiho, Sakata, Ken-ichiro, Ono, Yusuke, Mizukami, Yusuke, Kono, Toru, Kitagawa, Yoshimasa
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2024
• Subjects: beta-Defensins - genetics; Cells, Cultured; Dexamethasone; Dexamethasone - adverse effects; Hangeshashinto; Humans; IL-1α; Interleukin-1alpha - adverse effects; Interleukin-1alpha - genetics; Interleukin-1alpha - metabolism; Keratinocytes - metabolism; Lipopolysaccharides - adverse effects; Lipopolysaccharides - metabolism; NF-kappa B - metabolism; NF-kappa B - pharmacology; NF-kappa B - therapeutic use; Oral human keratinocyte; Stomatitis - chemically induced; Stomatitis - drug therapy; Stomatitis - metabolism; β-defensin 1; Oral human keratinocyte; Dexamethasone; Hangeshashinto; IL-1α; β-defensin 1
• ISSN: 1349-0079; 1880-3865
• DOI: 10.1016/j.job.2024.01.007

Human β-defensin 1 (hBD-1) is a antimicrobial peptide that is constantly secreted by oral tissues. Hangeshashinto (HST), a traditional Japanese medicine, has been reported to be effective against stomatitis. This study aimed to clarify the profile of HST by comparing the system of production of interleukin-1α (IL-1α) and hBD-1 in human oral mucosal epithelial cells with dexamethasone (DEX), a steroid used for the treatment of stomatitis. Human oral keratinocytes (HOK) were treated with HST, DEX, or HST components (baicalein, baicalin, berberine, and glycyrrhizin) for 24 h, and subsequently cultured for 24 h with or without Pam3CSK4 or lipopolysaccharide (LPS). The cell supernatants, total RNA, and intracellular proteins were collected, and changes in IL-1α and hBD-1 protein production and gene expression were evaluated using ELISA and RT-PCR. The phosphorylation of NF-kB and the cell proliferative ability of HOK were evaluated by western blotting and XTT assay, respectively. DEX (0.01–10 μM) significantly suppressed IL-1α and hBD-1 production induced by either Pam3CSK4 or LPS, and also decreased cell growth. In contrast, HST inhibited Pam3CSK4- and LPS-induced IL-1α production at a concentration range of 12.5–100 μg/mL without affecting the cell proliferative capacity and hBD-1 production of HOK. Baicalein and baicalin, which are flavonoid ingredients of HST, showed anti-IL-1α production. HST may be useful as a therapeutic agent for stomatitis and other inflammatory diseases of the oral cavity.