Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
Biochem Biophys Res Commun. 2013 Feb 15;431(3):506-11. doi: 10.1016/j.bbrc.2012.12.143. Epub 2013 Jan 16.
We investigated the molecular mechanism by which berberine reduces nitric oxide (NO) expression and high-mobility group box 1 (HMGB1) release in lipopolysaccharide (LPS)-induced macrophages. Berberine significantly inhibited the LPS-stimulated NO production and HMGB1 release in macrophages. In addition, berberine also induced heme oxygenase (HO)-1 in a dose-dependent manner, which was mediated through activation of p38 MAPK and NF-E2-related factor 2 (Nrf2) signaling cascade in macrophages. The inhibitory effect of berberine on LPS-stimulated NO and HMGB1 release was reversed by siRNA-Nrf2, SB203580 (p38 MAPK inhibitor) and zinc protoporphyrin (ZnPP; HO-1 inhibitor) within macrophages. Therefore, we conclude that berberine inhibits the proinflammatory response to LPS in macrophages by up-regulation of the HO-1 level, in which p38 MAPK and Nrf2 have an important role. These results suggest that berberine may be useful as a therapeutic agent for the treatment of inflammatory diseases.
我们研究了小檗碱降低脂多糖（LPS）诱导的巨噬细胞中一氧化氮（NO）表达和高迁移率族蛋白 B1（HMGB1）释放的分子机制。小檗碱显著抑制 LPS 刺激的巨噬细胞中 NO 的产生和 HMGB1 的释放。此外，小檗碱还以剂量依赖性方式诱导血红素加氧酶（HO）-1，这是通过激活巨噬细胞中 p38 MAPK 和核因子 E2 相关因子 2（Nrf2）信号级联来介导的。小檗碱对 LPS 刺激的 NO 和 HMGB1 释放的抑制作用可被 siRNA-Nrf2、SB203580（p38 MAPK 抑制剂）和锌原卟啉（HO-1 抑制剂）在巨噬细胞内逆转。因此，我们得出结论，小檗碱通过上调 HO-1 水平抑制巨噬细胞对 LPS 的促炎反应，其中 p38 MAPK 和 Nrf2 发挥重要作用。这些结果表明，小檗碱可能可作为治疗炎症性疾病的治疗剂。
