Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Gumjung-gu, Busan, Republic of Korea.
Biogerontology. 2012 Apr;13(2):133-45. doi: 10.1007/s10522-011-9361-4. Epub 2011 Oct 29.
Baicalin, a herb-derived flavonoid compound, has beneficial activities, including the modulation of oxidative stress and inflammation. Nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated transcription factor that plays an important role in regulating nuclear factor-κB (NF-κB)-induced age-related inflammation. We investigated the anti-inflammatory action of baicalin, which depends on its ability to activate PPARγ, and subsequently to suppress NF-κB. We examined baicalin-treated kidney tissue from 24-month-old Fischer 344 aged rats (10 or 20 mg/kg/day for 10 days) and baicalin-fed mice (10 mg/kg/day for 3 days) for in vivo investigations, and used endothelial YPEN-1 cells for in vitro studies. In the baicalin-fed aged rats, there was a marked enhancement of both nuclear protein levels and DNA binding activity of PPARγ, and a decreased expression of NF-κB target genes (VCAM-1, IL-1β, and IL-6) compared with non-baicalin-fed aged rats. Furthermore, to confirm the anti-inflammatory action of PPARγ activated by baicalin, we used lipopolysaccharide (LPS)-treated cells and mice. The results showed that baicalin induced PPARγ-selective activation in YPEN-1 cells, and that the effects of baicalin were blocked by the PPARγ receptor antagonist, GW9662. In addition, baicalin treatment prevented RS generation, NF-κB activation and the expression of pro-inflammatory genes, whereas it increased PPARγ expression in LPS-treated cells and mouse kidney. Our data suggest that baicalin-induced PPARγ expression reduced age-related inflammation through blocking pro-inflammatory NF-κB activation. These results indicate that baicalin is a novel PPARγ activator and that this agent may have the potential to minimize inflammation.
黄芩素是一种源自草药的类黄酮化合物，具有多种有益活性，包括调节氧化应激和炎症。核受体过氧化物酶体增殖物激活受体-γ（PPARγ）是一种配体激活的转录因子，在调节核因子-κB（NF-κB）诱导的与年龄相关的炎症中发挥重要作用。我们研究了黄芩素的抗炎作用，这种作用依赖于它激活 PPARγ 的能力，进而抑制 NF-κB。我们检测了经黄芩素处理的 24 月龄 Fischer 344 老年大鼠（10 或 20mg/kg/天，共 10 天）和黄芩素喂养的小鼠（10mg/kg/天，共 3 天）的肾脏组织，进行体内研究，并使用内皮细胞 YPEN-1 进行体外研究。在黄芩素喂养的老年大鼠中，与未用黄芩素喂养的老年大鼠相比，核蛋白水平和 PPARγ 的 DNA 结合活性明显增强，NF-κB 靶基因（VCAM-1、IL-1β 和 IL-6）的表达降低。此外，为了证实黄芩素激活的 PPARγ 的抗炎作用，我们使用脂多糖（LPS）处理的细胞和小鼠进行了研究。结果表明，黄芩素诱导 YPEN-1 细胞中 PPARγ 的选择性激活，并且这种作用被 PPARγ 受体拮抗剂 GW9662 阻断。此外，黄芩素处理可预防 LPS 处理的细胞和小鼠肾脏中 RS 的产生、NF-κB 的激活和促炎基因的表达，同时增加 PPARγ 的表达。我们的数据表明，黄芩素诱导的 PPARγ 表达通过阻断促炎 NF-κB 激活减少与年龄相关的炎症。这些结果表明，黄芩素是一种新型的 PPARγ 激活剂，该药物可能具有减轻炎症的潜力。
