Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China
Fitoterapia. 2011 Jun;82(4):709-15. doi: 10.1016/j.fitote.2011.02.011. Epub 2011 Mar 3.
Growing evidence suggests that TLRs/NF-κB signaling pathway plays a critical role in the pathogenesis of Crohn's disease (CD). We have reported that triptolide, an active component from Tripterygium wilfordii Hook, showed therapeutic activity in IL-10-deficeint (IL-10-/- mice, a murine CD model. However the full mechanisms of action of this agent in CD remain largely unknown. We hypothesized that triptolide would ameliorate the experimental colitis by inhibiting TLRs/NF-κB signaling pathway. We found TLR2 and TLR4 were upregulated in IL-10-)/- mice, triptolide inhibited the TLRs/NF-κB signaling pathway in vivo. In addition, triptolide in vitro was able to downregulate the TLRs/NF-κB pathway in cultured colonic explants from CD patients. Our results confirm the therapeutic effect of triptolide in experimental colitis, and suggest it as a promising compound for CD treatment. These findings also support the possibility that targeted inhibition of TLR signaling pathway is an approach deserving further investigation as a therapeutic strategy for CD.
越来越多的证据表明，TLR/NF-κB 信号通路在克罗恩病（CD）的发病机制中起着关键作用。我们曾报道，雷公藤红素是从雷公藤中提取的一种有效成分，在 IL-10 缺陷（IL-10-/-）小鼠（一种 CD 动物模型）中表现出治疗活性。然而，该药物在 CD 中的作用机制在很大程度上尚不清楚。我们假设雷公藤红素通过抑制 TLR/NF-κB 信号通路来改善实验性结肠炎。我们发现 TLR2 和 TLR4 在 IL-10-/-小鼠中上调，雷公藤红素在体内抑制 TLR/NF-κB 信号通路。此外，雷公藤红素在体外能够下调 CD 患者培养的结肠外植体中的 TLR/NF-κB 通路。我们的结果证实了雷公藤红素在实验性结肠炎中的治疗效果，并表明它是治疗 CD 的一种很有前途的化合物。这些发现还支持靶向抑制 TLR 信号通路作为治疗 CD 的一种治疗策略值得进一步研究的可能性。
