Song Yun Seon, Park Eun-Hee, Hur Gang Min, Ryu Young Sue, Kim Yong Man, Jin Changbae
Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, South Korea.
J Ethnopharmacol. 2002 May;80(2-3):155-61. doi: 10.1016/s0378-8741(02)00023-5.
Propolis obtained from honeybee hives has been used in Oriental folk medicine as an anti-inflammatory, anti-carcinogenic, or immunomodulatory agent. However, the molecular basis for anti-inflammatory properties of propolis has not yet been established. Since nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) has been known to be involved in inflammatory and autoimmune-mediated tissue destruction, modulation of NO synthesis or action represents a new approach to the treatment of inflammatory and autoimmune diseases. The present study, therefore, examined effects of ethanol extract of propolis (EEP) on iNOS expression and activity of iNOS enzyme itself. Treatment of RAW 264.7 cells with EEP significantly inhibited NO production and iNOS protein expression induced by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). EEP also inhibited iNOS mRNA expression and nuclear factor-kappa B (NF-kappaB) binding activity in a concentration-dependent manner. Furthermore, transfection of RAW 264.7 cells with iNOS promoter linked to a chloramphenicol acetyltransferase (CAT) reporter gene, revealed that EEP inhibited the iNOS promoter activity induced by LPS plus IFN-gamma through the NF-kappaB sites of the iNOS promoter. In addition, EEP directly interfered with the catalytic activity of murine recombinant iNOS enzyme. These results suggest that EEP may exert its anti-inflammatory effect by inhibiting the iNOS gene expression via action on the NF-kappaB sites in the iNOS promoter and by directly inhibiting the catalytic activity of iNOS.
从蜂巢中获取的蜂胶在东方民间医学中被用作抗炎、抗癌或免疫调节药物。然而，蜂胶抗炎特性的分子基础尚未确立。由于诱导型一氧化氮合酶（iNOS）合成的一氧化氮（NO）已知参与炎症和自身免疫介导的组织破坏，调节NO的合成或作用代表了一种治疗炎症和自身免疫性疾病的新方法。因此，本研究检测了蜂胶乙醇提取物（EEP）对iNOS表达及iNOS酶自身活性的影响。用EEP处理RAW 264.7细胞可显著抑制脂多糖（LPS）加干扰素-γ（IFN-γ）诱导的NO生成和iNOS蛋白表达。EEP还以浓度依赖的方式抑制iNOS mRNA表达和核因子-κB（NF-κB）结合活性。此外，用与氯霉素乙酰转移酶（CAT）报告基因相连的iNOS启动子转染RAW 264.7细胞，结果显示EEP通过iNOS启动子的NF-κB位点抑制LPS加IFN-γ诱导的iNOS启动子活性。另外，EEP直接干扰了小鼠重组iNOS酶的催化活性。这些结果表明，EEP可能通过作用于iNOS启动子中的NF-κB位点抑制iNOS基因表达以及直接抑制iNOS的催化活性来发挥其抗炎作用。
