Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
J Ethnopharmacol. 2011 Oct 11;137(3):1197-206. doi: 10.1016/j.jep.2011.07.048. Epub 2011 Aug 2.
Phaseolus angularis Wight (adzuki bean) is an ethnopharmacologically well-known folk medicine that is prescribed for infection, edema, and inflammation of the joints, appendix, kidney and bladder in Korea, China and Japan.
The anti-inflammatory effect of this plant and its associated molecular mechanisms will be investigated.
The immunomodulatory activity of Phaseolus angularis ethanol extract (Pa-EE) in toll like receptor (TLR)-activated macrophages induced by ligands such as lipopolysaccharide (LPS), Poly (I:C), and pam3CSK was investigated by assessing nitric oxide (NO) and prostaglandin (PG)E(2) levels. To identify which transcription factors such as nuclear factor (NF)-κB and their signaling enzymes can be targeted to Pa-EE, biochemical approaches including reporter gene assays, immunoprecipitation, kinase assays, and immunoblot analyses were also employed. Finally, whether Pa-EE was orally available, ethanol (EtOH)/hydrochloric acid (HCl)-induced gastritis model in mice was used.
Pa-EE dose-dependently suppressed the release of PGE(2) and NO in LPS-, Poly(I:C)-, and pam3CSK-activated macrophages. Pa-EE strongly down-regulated LPS-induced mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Interestingly, Pa-EE markedly inhibited NF-κB, activator protein (AP)-1, and cAMP response element binding protein (CREB) activation; further, according to direct kinase assays and immunoblot analyses, Pa-EE blocked the activation of the upstream signaling molecules spleen tyrosine kinase (Syk), p38, and transforming growth factor β-activated kinase 1 (TAK1). Finally, orally administered Pa-EE clearly ameliorated EtOH/HCl-induced gastritis in mice.
Our results suggest that Pa-EE can be further developed as a promising anti-inflammatory remedy because it targets multiple inflammatory signaling enzymes and transcription factors.
Phaseolus angularis Wight(菜豆)
Phaseolus angularis Wight(菜豆)在韩国、中国和日本被广泛应用于民间医学,用于治疗感染、水肿和关节、阑尾、肾脏和膀胱炎症。
研究该植物的抗炎作用及其相关的分子机制。
通过评估脂多糖(LPS)、聚(I:C)和 pam3CSK 等配体激活的 Toll 样受体(TLR)-激活的巨噬细胞中一氧化氮(NO)和前列腺素(PG)E(2)水平,研究 Phaseolus angularis 乙醇提取物(Pa-EE)的免疫调节活性。为了确定哪些转录因子,如核因子(NF)-κB 和它们的信号酶可以成为 Pa-EE 的靶点,还采用了生化方法,包括报告基因检测、免疫沉淀、激酶检测和免疫印迹分析。最后,还使用了 Pa-EE 是否可口服、乙醇(EtOH)/盐酸(HCl)诱导的小鼠胃炎模型。
Pa-EE 呈剂量依赖性抑制 LPS、Poly(I:C)和 pam3CSK 激活的巨噬细胞中 PGE(2)和 NO 的释放。Pa-EE 强烈下调 LPS 诱导的诱导型一氧化氮合酶(iNOS)和环氧化酶(COX)-2 的 mRNA 表达。有趣的是,Pa-EE 明显抑制 NF-κB、激活蛋白(AP)-1 和 cAMP 反应元件结合蛋白(CREB)的激活;此外,根据直接激酶检测和免疫印迹分析,Pa-EE 阻断了上游信号分子脾酪氨酸激酶(Syk)、p38 和转化生长因子β激活激酶 1(TAK1)的激活。最后,口服给予 Pa-EE 可明显改善小鼠 EtOH/HCl 诱导的胃炎。
我们的结果表明,Pa-EE 可以进一步开发为一种有前途的抗炎药物,因为它针对多种炎症信号酶和转录因子。