Kang Bok Yun, Chung Su Wol, Kim Seung Hyun, Cho Daeho, Kim Tae Sung
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju, Republic of Korea.
Planta Med. 2003 Aug;69(8):687-91. doi: 10.1055/s-2003-42779.
Pharmacological inhibition of interleukin-12 (IL-12) production may be a therapeutic strategy for preventing development and progression of disease in experimental models of autoimmunity. In this study we investigated the effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on the production of IL-12 from mouse macrophages stimulated with lipopolysaccharide (LPS). Baicalein potently inhibited the LPS-induced IL-12 production from both primary macrophages and RAW264.7 monocytic cell-line in a dose-dependent manner (the IC50 values were 43.7 and 17.4 microM, respectively). The effect of baicalein on IL-12 gene promoter activation was analyzed by transfecting RAW264.7 cells with IL-12 gene promoter/luciferase constructs. The repressive effect mapped to a region in the IL-12 gene promoter containing a binding site for NF-kappaB. Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the NF-kappaB site, which significantly decreased upon addition of baicalein, indicating that baicalein inhibited IL-12 production in LPS-activated macrophages via inhibition of NF-kappaB binding activity.
在自身免疫性疾病的实验模型中，对白介素12（IL-12）产生进行药理学抑制可能是预防疾病发展和进展的一种治疗策略。在本研究中，我们调查了黄芩根中存在的一种黄酮类化合物黄芩素对脂多糖（LPS）刺激的小鼠巨噬细胞产生IL-12的影响。黄芩素以剂量依赖性方式有效抑制原代巨噬细胞和RAW264.7单核细胞系中LPS诱导的IL-12产生（IC50值分别为43.7和17.4 microM）。通过用IL-12基因启动子/荧光素酶构建体转染RAW264.7细胞，分析了黄芩素对IL-12基因启动子激活的影响。抑制作用定位于IL-12基因启动子中含有NF-κB结合位点的区域。此外，LPS激活巨噬细胞导致与NF-κB位点的结合活性显著增强，加入黄芩素后该活性显著降低，表明黄芩素通过抑制NF-κB结合活性抑制LPS激活的巨噬细胞中IL-12的产生。
