Department of Biotechnology, Zhengzhou University, Zhengzhou 450001, China.
Int Immunopharmacol. 2011 Dec;11(12):2144-9. doi: 10.1016/j.intimp.2011.09.010. Epub 2011 Oct 6.
Andrographolide (1) is a major diterpene lactone exhibiting anti-inflammatory effects and is found in the plant Andrographis paniculata (Burm. f) Nees, which is widely used in Traditional Chinese Medicine. Synthesis of more effective drugs from andrographolide is very interesting and can prove to be highly useful. In this study, we investigated the anti-inflammatory effects of andrographolide and its derivatives (compounds 2-6) through dimethylbenzene-induced ear edema in mice. Substances under study were administrated intragastrically and the structure-activity relationship was analyzed. Results showed that compounds 5 and 6 significantly inhibited ear edema compared with compound 1 (p<0.05), indicating that the introduction of p-Chlorobenzylidene to C-15 of compound 2 enhances the anti-inflammatory effect. Moreover, compound 6 exhibited the strongest anti-inflammatory effect against ear edema in mice (79.4%; 1.35 mmol/kg, ig) and paw edema in rats (50.4%; 0.90 mmol/kg, ig). In addition, compound 6 significantly (p<0.05) inhibited granuloma formation and reduced the increase in vascular permeability induced by peritoneal injection of 0.6% acetic acid solution in mice. Findings indicate that compound 6 exerts its enhanced anti-inflammatory effects by decreasing serum iNOS activity, NO production, and PGE(2) production.
穿心莲内酯（1）是一种主要的二萜内酯，具有抗炎作用，存在于植物穿心莲（Burm. f）Nees 中，广泛用于中药。从穿心莲内酯合成更有效的药物非常有趣，并且可能非常有用。在这项研究中，我们通过二甲苯诱导的小鼠耳肿胀研究了穿心莲内酯及其衍生物（化合物 2-6）的抗炎作用。研究的物质通过灌胃给药，并分析了结构-活性关系。结果表明，与化合物 1 相比，化合物 5 和 6 显著抑制了耳肿胀（p<0.05），表明将 p-氯苯亚甲基引入到化合物 2 的 C-15 位增强了抗炎作用。此外，化合物 6 对二甲苯诱导的小鼠耳肿胀（79.4%；1.35 mmol/kg，ig）和大鼠足肿胀（50.4%；0.90 mmol/kg，ig）具有最强的抗炎作用。此外，化合物 6 显著（p<0.05）抑制了肉芽肿的形成，并降低了腹腔注射 0.6%醋酸溶液引起的血管通透性增加。研究结果表明，化合物 6 通过降低血清 iNOS 活性、NO 生成和 PGE（2）生成来发挥增强的抗炎作用。
