Du Crystal Y Q, Choi Roy C Y, Dong Tina T X, Lau David T W, Tsim Karl W K
Division of Life Science and Centre for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong SAR, China.
PLoS One. 2014 Jun 26;9(6):e100382. doi: 10.1371/journal.pone.0100382. eCollection 2014.
Yu Ping Feng San (YPFS), a Chinese herbal decoction comprising Astragali Radix (AR; Huangqi), Atractylodis Macrocephalae Rhizoma (AMR; Baizhu), and Saposhnikoviae Radix (SR; Fangfeng), has been used clinically to treat inflammatory bowel diseases (IBD). Previously, we demonstrated a dual role of YPFS in regulating cytokine release in cultured macrophages. In this study, we elucidated the anti-inflammatory effect of YPFS that is mediated through modulating the expression of three key enzymes involved in IBD: inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intestinal alkaline phosphatase (IALP). In a lipopolysaccharide (LPS)-induced chronic-inflammation model of cultured murine macrophages, YPFS treatment suppressed the activation of iNOS and COX-2 expression in a dose-dependent manner. Conversely, application of YPFS in cultured small intestinal enterocytes markedly induced the expression of IALP in a time-dependent manner, which might strengthen the intestinal detoxification system. A duality of YPFS in modulating the expression of iNOS and COX-2 was determined here. The expression of iNOS and COX-2 in macrophages was induced by YPFS, and this activation was partially blocked by the NF-κB-specific inhibitor BAY 11-7082, indicating a role of NF-κB signaling. These YPFS-induced changes in gene regulation strongly suggest that the anti-inflammatory effects of YPFS are mediated through the regulation of inflammatory enzymes.
玉屏风散(YPFS)是一种由黄芪(AR;黄芪)、白术(AMR;白术)和防风(SR;防风)组成的中药汤剂,已在临床上用于治疗炎症性肠病(IBD)。此前,我们证明了玉屏风散在调节培养的巨噬细胞中细胞因子释放方面具有双重作用。在本研究中,我们阐明了玉屏风散通过调节IBD中涉及的三种关键酶的表达介导的抗炎作用:诱导型一氧化氮合酶(iNOS)、环氧化酶-2(COX-2)和肠碱性磷酸酶(IALP)。在脂多糖(LPS)诱导的培养小鼠巨噬细胞慢性炎症模型中,玉屏风散处理以剂量依赖性方式抑制iNOS的激活和COX-2的表达。相反,在培养的小肠肠上皮细胞中应用玉屏风散以时间依赖性方式显著诱导IALP的表达,这可能会加强肠道解毒系统。本文确定了玉屏风散在调节iNOS和COX-2表达方面的双重性。玉屏风散诱导巨噬细胞中iNOS和COX-2的表达,并且这种激活被NF-κB特异性抑制剂BAY 11-7082部分阻断,表明NF-κB信号传导起作用。这些玉屏风散诱导的基因调节变化强烈表明,玉屏风散的抗炎作用是通过调节炎症酶介导的。