Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea.
Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Korea.
Int J Mol Sci. 2021 Mar 25;22(7):3385. doi: 10.3390/ijms22073385.
() classified as a class I carcinogen by the World Health Organization (WHO) plays an important role in the progression of chronic gastritis and the development of gastric cancer. A major bioactive component of , evodiamine, has been known for its anti-bacterial effect and anti-cancer effects. However, the inhibitory effect of evodiamine against is not yet known and the inhibitory mechanisms of evodiamine against gastric cancer cells are yet to be elucidated concretely. In this study, therefore, anti-bacterial effect of evodiamine on growth and its inhibitory mechanisms as well as anti-inflammatory effects and its mechanisms of evodiamine on -induced inflammation were investigated in vitr. Results of this study showed the growth of the reference strains and clinical isolates were inhibited by evodiamine. It was considered one of the inhibitory mechanisms that evodiamine downregulated both gene expressions of replication and transcription machineries of . Treatment of evodiamine also induced downregulation of urease and diminished translocation of cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) proteins into gastric adenocarcinoma (AGS) cells. This may be resulted from the reduction of CagA and VacA expressions as well as the type IV secretion system (T4SS) components and secretion system subunit protein A (SecA) protein which are involved in translocation of CagA and VacA into host cells, respectively. In particular, evodiamine inhibited the activation of signaling proteins such as the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway induced by infection. It consequently might contribute to reduction of interleukin (IL)-8 production in AGS cells. Collectively, these results suggest anti-bacterial and anti-inflammatory effects of evodiamine against .
（）被世界卫生组织（WHO）列为 I 类致癌物质，在慢性胃炎的进展和胃癌的发展中起重要作用。作为的主要生物活性成分，吴茱萸碱具有抗菌作用和抗癌作用。然而，吴茱萸碱对的抑制作用尚不清楚，其对胃癌细胞的抑制机制也尚未具体阐明。因此，本研究在体外研究了吴茱萸碱对生长的抗菌作用及其抑制机制，以及吴茱萸碱对诱导炎症的抗炎作用及其机制。本研究结果表明，吴茱萸碱抑制参考株和临床分离株的生长。认为其抑制机制之一是吴茱萸碱下调的复制和转录机制的基因表达。吴茱萸碱的治疗还诱导了尿素酶的下调，并减少了细胞毒素相关抗原 A（CagA）和空泡毒素 A（VacA）蛋白向胃腺癌（AGS）细胞的易位。这可能是由于 CagA 和 VacA 表达以及涉及 CagA 和 VacA 易位到宿主细胞的 IV 型分泌系统（T4SS）组件和分泌系统亚基蛋白 A（SecA）蛋白的减少所致。特别是，吴茱萸碱抑制了由感染诱导的核因子κ轻链增强子的激活 B 细胞（NF-κB）和丝裂原激活蛋白激酶（MAPK）途径的信号蛋白的激活。因此，它可能有助于减少 AGS 细胞中白细胞介素（IL）-8 的产生。总的来说，这些结果表明吴茱萸碱对具有抗菌和抗炎作用。
