Lee Seung Ho, Lee Sun Young, Son Dong Ju, Lee Heesoon, Yoo Hwan Soo, Song Sukgil, Oh Ki Wan, Han Dong Cho, Kwon Byoung Mog, Hong Jin Tae
College of Pharmacy, Chungbuk National University, Heungduk-gu, Cheongju 361-763, South Korea.
Biochem Pharmacol. 2005 Mar 1;69(5):791-9. doi: 10.1016/j.bcp.2004.11.013. Epub 2005 Jan 16.
Cinnamomum cassia has been widely used for treating dyspepsia, gastritis, and inflammatory disease. In the present study, several of cinnamaldehyde derivatives were synthesized from various cinnamic acid based on the 2'-hydroxycinnamaldehyde isolated from the bark C. cassia Blume was investigated to compare their NO production and NF-kappa B activity from Raw 264.7 cell since nitric oxide (NO) and NF-kappa B have been shown to be implicated factors in the inflammatory disease. The results show that HCA, among the derivatives, most significantly inhibited lipopolysaccharide (LPS)-induced NO production and NF-kappa B transcriptional activity in a dose-dependent manner with an IC(50) value of 8 and 22 microM, respectively. We next investigated putative possible mechanisms of inhibitory effect of HCA on NO production. The inhibition of NO by HCA was consistent with the inhibitory effect on LPS-induced inducible nitric oxide synthase (iNOS) expression. Moreover, HCA inhibited LPS-induced p50 and p65 translocation resulting in the inhibition of the DNA binding activity of the NF-kappa B, a central regulator of iNOS. The present results provided evidence that HCA, among cinnamaledhyde derivatives, has the most inhibitory effect on NO production through inhibition of NF-kappa B activation, and thus can be used as an anti-inflammatory agent.
肉桂已被广泛用于治疗消化不良、胃炎和炎症性疾病。在本研究中，基于从肉桂树皮中分离出的2'-羟基肉桂醛，由各种肉桂酸合成了几种肉桂醛衍生物，对其进行了研究，以比较它们对Raw 264.7细胞中一氧化氮（NO）生成和核因子κB（NF-κB）活性的影响，因为一氧化氮（NO）和核因子κB已被证明是炎症性疾病的相关因素。结果表明，在这些衍生物中，HCA以剂量依赖性方式最显著地抑制脂多糖（LPS）诱导的NO生成和NF-κB转录活性，IC50值分别为8和22微摩尔。接下来，我们研究了HCA对NO生成抑制作用的可能机制。HCA对NO的抑制作用与对LPS诱导的诱导型一氧化氮合酶（iNOS）表达的抑制作用一致。此外，HCA抑制LPS诱导的p50和p65易位，从而抑制iNOS的核心调节因子NF-κB的DNA结合活性。目前的结果提供了证据，表明在肉桂醛衍生物中，HCA通过抑制NF-κB激活对NO生成具有最大的抑制作用，因此可作为一种抗炎剂。
