Ohtani Masahiro, Nishimura Tsubasa
Central Research Institute, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Hiroshima 739-1195, Japan.
Biomed Rep. 2020 Mar;12(3):99-108. doi: 10.3892/br.2019.1269. Epub 2019 Dec 30.
Aged garlic extract (AGE) contains various biologically active sulfur-containing amino acids, such as -allylcysteine (SAC), -1-propenylcysteine (S1PC) and -allylmercaptocysteine (SAMC). These amino acids have been demonstrated to lower hypertension, improve atherosclerosis and enhance immunity through their anti-inflammatory and antioxidant activities. It was recently reported that the administration of AGE alleviated gingivitis in a clinical trial. In this study, to gain insight into this effect of AGE, the authors examined whether AGE and the three above-mentioned sulfur compounds influence the effects of tumor necrosis factor-α (TNF-α) in inducing intercellular adhesion molecule-1 (ICAM-1) expression and interleukin-6 (IL-6) secretion in Ca9-22 human gingival epithelial cells. It was found that S1PC reduced the level of ICAM-1 protein induced by TNF-α possibly through post-translational levels without affecting the TNF-α-induced mRNA expression. However, SAC and SAMC had no effect. It was also confirmed the inhibitory effect of an antimicrobial peptide [human-β defensin-3 (hβD3)] and found that the inhibitory effects of hbD3 and S1PC were synergistic. On the other hand, the TNF-α-induced IL-6 secretion was attenuated by SAC and SAMC in a dose-dependent manner, whereas S1PC was ineffective. In addition, SAC and SAMC, but not S1PC inhibited the phosphorylation of the transcription factor nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), which is involved in the expression of inflammatory molecules, suggesting that the anti-inflammatory effects of SAC and SAMC are mediated, at least partly, by NF-κB. On the whole, the findings of this study suggest that the three sulfur amino acids in AGE function synergistically in alleviating inflammation in human gingival epithelial cells.
aged garlic extract (AGE) 含有多种具有生物活性的含硫氨基酸,如S-烯丙基半胱氨酸(SAC)、S-1-丙烯基半胱氨酸(S1PC)和S-烯丙基巯基半胱氨酸(SAMC)。这些氨基酸已被证明可通过其抗炎和抗氧化活性降低高血压、改善动脉粥样硬化并增强免疫力。最近有报道称,在一项临床试验中,AGE的给药减轻了牙龈炎。在本研究中,为了深入了解AGE的这种作用,作者研究了AGE和上述三种硫化合物是否会影响肿瘤坏死因子-α(TNF-α)诱导人牙龈上皮细胞Ca9-22中细胞间黏附分子-1(ICAM-1)表达和白细胞介素-6(IL-6)分泌的作用。结果发现,S1PC可能通过翻译后水平降低了TNF-α诱导的ICAM-1蛋白水平,而不影响TNF-α诱导的mRNA表达。然而,SAC和SAMC没有作用。还证实了一种抗菌肽[人β-防御素-3(hβD3)]的抑制作用,并发现hβD3和S1PC的抑制作用具有协同性。另一方面,SAC和SAMC以剂量依赖性方式减弱了TNF-α诱导的IL-6分泌,而S1PC无效。此外,SAC和SAMC而非S1PC抑制了参与炎症分子表达的转录因子核因子κB轻链增强子(NF-κB)的磷酸化,这表明SAC和SAMC的抗炎作用至少部分是由NF-κB介导的。总体而言,本研究结果表明,AGE中的三种硫氨基酸在减轻人牙龈上皮细胞炎症方面具有协同作用。