Jeong Jin-Woo, Choi Il-Whan, Jo Guk-Heui, Kim Gi-Young, Kim Jinwoo, Suh Hongsuk, Ryu Chung-Ho, Kim Wun-Jae, Park Kun-Young, Choi Yung Hyun
1Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, Korea.
2Department of Microbiology, College of Medicine, Inje University, Busan, Korea.
J Med Food. 2015 Jun;18(6):677-84. doi: 10.1089/jmf.2014.3275. Epub 2015 Apr 28.
We investigated the protective ability of 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA), an active principle in Korean cabbage kimchi, against the production of proinflammatory mediators and cytokines, and the mechanisms involved in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. HDMPPA significantly suppressed the production of nitric oxide (NO) and prostaglandin E2, along with the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated BV2 cells, at concentrations with no cytotoxicity. HDMPPA also attenuated the LPS-induced expression and secretion of proinflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β. Furthermore, HDMPPA inhibited LPS-induced nuclear factor-κB (NF-κB) activation, which was associated with the abrogation of IκB-α degradation and phosphorylation, and subsequent decreases in NF-κB p65 levels. Moreover, the phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, a downstream molecule of phosphatidylinositol-3-kinase (PI3K), in LPS-stimulated BV2 cells was suppressed markedly by HDMPPA. This effect was associated with a significant reduction in the formation of intracellular reactive oxygen species. The findings in this study suggest that HDMPPA may exert anti-inflammatory responses by suppressing LPS-induced expression of proinflammatory mediators and cytokines through blockage of NF-κB, MAPKs, and PI3K/Akt signaling pathways and oxidative stress in microglia.
我们研究了韩国泡菜中的活性成分3-(4'-羟基-3',5'-二甲氧基苯基)丙酸(HDMPPA)对促炎介质和细胞因子产生的保护能力,以及脂多糖(LPS)刺激的BV2小胶质细胞中涉及的机制。HDMPPA在无细胞毒性的浓度下,显著抑制了LPS刺激的BV2细胞中一氧化氮(NO)和前列腺素E2的产生,以及诱导型NO合酶和环氧化酶-2的表达。HDMPPA还减弱了LPS诱导的促炎细胞因子如肿瘤坏死因子-α和白细胞介素-1β的表达和分泌。此外,HDMPPA抑制了LPS诱导的核因子-κB(NF-κB)激活,这与IκB-α降解和磷酸化的消除以及随后NF-κB p65水平的降低有关。此外,HDMPPA显著抑制了LPS刺激的BV2细胞中丝裂原活化蛋白激酶(MAPKs)和磷脂酰肌醇-3激酶(PI3K)下游分子Akt的磷酸化。这种作用与细胞内活性氧的形成显著减少有关。本研究结果表明,HDMPPA可能通过阻断小胶质细胞中NF-κB、MAPKs和PI3K/Akt信号通路以及氧化应激,抑制LPS诱导的促炎介质和细胞因子的表达,从而发挥抗炎反应。