College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
Free Radic Res. 2011 May;45(5):507-17. doi: 10.3109/10715762.2011.555479. Epub 2011 Feb 1.
The bioactive flavonoid baicalein has been shown to have radioprotective activity, although the molecular mechanism is poorly understood in vivo. C57BL/6 mice were irradiated with X-rays (15 Gy) with and without baicalein treatment (5 mg/kg/day). Irradiation groups showed an increase of NF-κB-mediated inflammatory factors with oxidative damage and showed inactivation of FOXO and its target genes, catalase and SOD. However, baicalein suppressed radiation-induced inflammatory response by negatively regulating NF-κB and up-regulating FOXO activation and catalase and SOD activities. Furthermore, baicalein inhibited radiation-induced phosphorylation of MAPKs and Akt, which are the upstream kinases of NF-κB and FOXOs. Based on these findings, it is concluded that baicalein has a radioprotective effect against NF-κB-mediated inflammatory response through MAPKs and the Akt pathway, which is accompanied by the protective effects on FOXO and its target genes, catalase and SOD. Thus, these findings provide new insights into the molecular mechanism underlying the radioprotective role of baicalein in mice.
已经有研究表明,生物活性黄酮黄芩素具有放射防护活性,尽管其在体内的分子机制尚不清楚。用 X 射线(15Gy)照射 C57BL/6 小鼠,并在照射的同时给予黄芩素处理(5mg/kg/天)。照射组表现出 NF-κB 介导的炎症因子增加,伴有氧化损伤,并出现 FOXO 及其靶基因、过氧化氢酶和 SOD 的失活。然而,黄芩素通过负调控 NF-κB 和上调 FOXO 激活以及过氧化氢酶和 SOD 活性,抑制了辐射诱导的炎症反应。此外,黄芩素抑制了 MAPKs 和 Akt 的磷酸化,MAPKs 和 Akt 是 NF-κB 和 FOXOs 的上游激酶。基于这些发现,可以得出结论,黄芩素通过 MAPKs 和 Akt 通路对 NF-κB 介导的炎症反应具有放射防护作用,同时对 FOXO 和其靶基因、过氧化氢酶和 SOD 具有保护作用。因此,这些发现为黄芩素在小鼠中的放射防护作用的分子机制提供了新的见解。