Mieda Katsuhiro, Nakanishi Tadashi, Kuramoto Hitomi, Hosokawa Yoshitaka, Hosokawa Ikuko, Takegawa Daisuke, Hosaka Keiichi
Department of Regenerative Dental Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Department of Pediatric Dentistry, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Cell Biochem Biophys. 2025 Jun;83(2):2431-2439. doi: 10.1007/s12013-024-01652-8. Epub 2024 Dec 30.
Sudachitin, which is a polymethoxy flavonoid derived from the peer of Citrus sudachi, has several biological properties. However, the effect of sudachitin on human dental pulp cells (HDPCs) remains unclear. The aim of this study was to investigate whether sudachitin could decrease the expression of inflammatory mediators such as cytokines and prostaglandin in HDPCs stimulated with Pam3CSK4, a ligand for toll-like receptor (TLR) 2. HDPCs were pre-incubated with different concentrations of sudachitin (6.25, 12.5, 25, or 50 μM) and stimulated with Pam3CSK4 (100 ng/mL). The quantification of inflammatory cytokines (interleukin (IL)-6, IL-8, and C-X-C motif chemokine ligand (CXCL) 10) and prostaglandin E (PGE) were performed by enzyme-linked immunosorbent assay (ELISA). The expression of cyclooxygenase (COX)-2, a key enzyme for PGE formation, was analyzed by western blot. Moreover, the activations of cell signal pathways were examined by western blot analysis. Sudachitin suppressed IL-6, IL-8, CXCL10, and PGE production and COX-2 protein expression in Pam3CSK4-stimulated HDPCs. In addition, we revealed that nuclear factor-kappa B (NF-κB) and protein kinase B (Akt) pathways in the Pam3CSK4-stimulated HDPCs were inhibited by sudachitin treatment. These findings suggest that sudachitin can reduce inflammatory mediator production in HDPCs stimulated with TLR2 ligand by inhibiting NF-κB and Akt activations.
紫苏素是一种从酸橘的同类植物中提取的多甲氧基黄酮，具有多种生物学特性。然而，紫苏素对人牙髓细胞（HDPCs）的影响尚不清楚。本研究的目的是探讨紫苏素是否能降低经Toll样受体（TLR）2配体Pam3CSK4刺激的HDPCs中细胞因子和前列腺素等炎症介质的表达。HDPCs先用不同浓度的紫苏素（6.25、12.5、25或50μM）预孵育，然后用Pam3CSK4（100 ng/mL）刺激。通过酶联免疫吸附测定（ELISA）对炎症细胞因子（白细胞介素（IL）-6、IL-8和C-X-C基序趋化因子配体（CXCL）10）和前列腺素E（PGE）进行定量分析。通过蛋白质印迹法分析前列腺素E合成关键酶环氧化酶（COX）-2的表达。此外，通过蛋白质印迹分析检测细胞信号通路的激活情况。紫苏素可抑制Pam3CSK4刺激的HDPCs中IL-6、IL-8、CXCL10和PGE的产生以及COX-2蛋白的表达。此外，我们发现紫苏素处理可抑制Pam3CSK4刺激的HDPCs中的核因子κB（NF-κB）和蛋白激酶B（Akt）信号通路。这些研究结果表明，紫苏素可通过抑制NF-κB和Akt的激活来减少TLR2配体刺激的HDPCs中炎症介质的产生。
