Bai Se-Kyung, Lee Seon-Jin, Na Hee-Jun, Ha Kwon-Soo, Han Jeong-A, Lee Hansoo, Kwon Young-Guen, Chung Cha-Kwon, Kim Young-Myeong
Vascular System Research Center, Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do 200-701, Korea.
Exp Mol Med. 2005 Aug 31;37(4):323-34. doi: 10.1038/emm.2005.42.
beta-Carotene has shown antioxidant and anti-inflammatory activities; however, its molecular mechanism has not been clearly defined. We examined in vitro and in vivo regulatory function of beta-carotene on the production of nitric oxide (NO) and PGE(2) as well as expression of inducible NO synthase (iNOS), cyclooxygenase-2, TNF-alpha, and IL-1beta. beta-Carotene inhibited the expression and production of these inflammatory mediators in both LPS-stimulated RAW264.7 cells and primary macrophages in a dose-dependent fashion as well as in LPS-administrated mice. Furthermore, this compound suppressed NF-kappaB activation and iNOS promoter activity in RAW264.7 cells stimulated with LPS. beta-Carotene blocked nuclear translocation of NF-kappaB p65 subunit, which correlated with its inhibitory effect on IkappaBalpha phosphorylation and degradation. This compound directly blocked the intracellular accumulation of reactive oxygen species in RAW264.7 cells stimulated with LPS as both the NADPH oxidase inhibitor diphenylene iodonium and antioxidant pyrrolidine dithiocarbamate did. The inhibition of NADPH oxidase also inhibited NO production, iNOS expression, and iNOS promoter activity. These results suggest that beta-carotene possesses anti-inflammatory activity by functioning as a potential inhibitor for redox-based NF-kappaB activation, probably due to its antioxidant activity.
β-胡萝卜素已显示出抗氧化和抗炎活性；然而，其分子机制尚未明确界定。我们研究了β-胡萝卜素在体外和体内对一氧化氮（NO）和前列腺素E2（PGE2）生成以及诱导型一氧化氮合酶（iNOS）、环氧化酶-2、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）表达的调节功能。β-胡萝卜素在脂多糖（LPS）刺激的RAW264.7细胞和原代巨噬细胞中以及在给予LPS的小鼠体内，均以剂量依赖的方式抑制这些炎症介质的表达和生成。此外，该化合物在LPS刺激的RAW264.7细胞中抑制核因子-κB（NF-κB）激活和iNOS启动子活性。β-胡萝卜素阻断NF-κB p65亚基的核转位，这与其对IκBα磷酸化和降解的抑制作用相关。该化合物如同NADPH氧化酶抑制剂二苯基碘鎓和抗氧化剂吡咯烷二硫代氨基甲酸盐一样，直接阻断LPS刺激的RAW264.7细胞中活性氧的细胞内积累。抑制NADPH氧化酶也抑制NO生成、iNOS表达和iNOS启动子活性。这些结果表明，β-胡萝卜素可能因其抗氧化活性，作为基于氧化还原的NF-κB激活的潜在抑制剂而具有抗炎活性。
