Nobiletin, a biologically active substance in the skin of citrus fruits, has been reported to be an effective anti-inflammatory, anticancer, and antimicrobial agent. In this study, we aimed to examine the anti-inflammatory effects of nobiletin on tumor necrosis factor- (TNF-) stimulated human periodontal ligament cells (HPDLCs). Our results demonstrated that nobiletin treatment could decrease the expressions of inflammatory cytokines (C-X-C motif chemokine ligand (CXCL)10, C-C motif chemokine ligand (CCL)2, and interleukin- (IL-) 8), matrix metalloproteinases (MMPs) (MMP1 and MMP3), and prostaglandin-endoperoxide synthase 2 (PTGS2) in TNF-stimulated HPDLCs. Moreover, we revealed that nobiletin could inhibit the activation of nuclear factor- (NF-) κB and protein kinase B (AKT1) pathways in TNF-stimulated HPDLCs. Furthermore, nobiletin treatment enhanced nuclear factor, erythroid 2 like 2 (NFE2L2) and heme oxygenase 1 (HMOX1) expressions in TNF-stimulated HPDLCs. In conclusion, these findings suggest that nobiletin can inhibit inflammatory responses in TNF-stimulated HPDLCs by inhibiting NF-κB and AKT1 activations and upregulating the NFE2L2 and HMOX1 expression.

中文翻译：

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Nobiletin 降低肿瘤坏死因子刺激的人牙周膜细胞中炎症介质的表达

Nobiletin 是柑橘类水果皮中的一种生物活性物质，据报道是一种有效的抗炎、抗癌和抗菌剂。在这项研究中，我们旨在检查 nobiletin 对肿瘤坏死因子 (TNF-) 刺激的人牙周膜细胞 (HPDLCs) 的抗炎作用。我们的结果表明，nobiletin 治疗可以降低炎性细胞因子（CXC 基序趋化因子配体 (CXCL)10、CC 基序趋化因子配体 (CCL)2 和白细胞介素- (IL-) 8）、基质金属蛋白酶 (MMPs) (MMP1 和MMP3) 和 TNF 刺激的 HPDLCs 中的前列腺素内过氧化物合酶 2 (PTGS2)。此外，我们发现 nobiletin 可以抑制核因子- (NF-) κ的激活。TNF 刺激的 HPDLCs 中的 B 和蛋白激酶 B (AKT1) 通路。此外，nobiletin 治疗增强了 TNF 刺激的 HPDLCs 中核因子、红细胞 2 样 2 (NFE2L2) 和血红素加氧酶 1 (HMOX1) 的表达。总之，这些研究结果表明，nobiletin 可以通过抑制 NF-κB 和 AKT1 激活并上调 NFE2L2 和 HMOX1 表达来抑制 TNF 刺激的 HPDLCs 中的炎症反应。