Ren Zhenghua, Wang Lei, Cui Jianhua, Huoc Zeren, Xue Jinru, Cui Hao, Mao Qiqi, Yang Rirong
Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou, China.
Pharmazie. 2013 Aug;68(8):689-94.
Resveratrol has been shown to possess multiple pharmacological activities including anti-tumor, anti-inflammation and immunomodulation, and participates in the regulation of the NF-kappaB signaling pathway. However, the mechanism of the NF-kappaB signaling pathway inhibited by resveratrol remains obscure. In this study, we first examined the effect of resveratrol on endogenous and TNF-alpha-induced NF-kappaB activation, and found that resveratrol suppressed NF-kappaB activation in a dose dependent manner. Resveratrol reduced the transcriptional activity of p65, but neither affected the DNA-binding activity of NF-kappaB nor blocked the nuclear translocation of p65. Moreover, resveratrol had no effect on the expression level of IkappaBalpha protein and inhibited IkappaBalpha degradation. Further investigation revealed that resveratrol blocked the ubiquitination of NEMO and inhibited IkappaB kinase(beta)-mediated NF-kappaB activation. These results demonstrated that resveratrol effectively suppressed NF-kappaB signaling through inhibiting the activities of NF-kappaB and IkappaB kinase. Therefore, resveratrol may provide a novel approach to treating inflammation-associated diseases and cancer.
白藜芦醇已被证明具有多种药理活性，包括抗肿瘤、抗炎和免疫调节，并参与核因子κB信号通路的调控。然而，白藜芦醇抑制核因子κB信号通路的机制仍不清楚。在本研究中，我们首先检测了白藜芦醇对内源性和肿瘤坏死因子α诱导的核因子κB激活的影响，发现白藜芦醇以剂量依赖的方式抑制核因子κB激活。白藜芦醇降低了p65的转录活性，但既不影响核因子κB的DNA结合活性，也不阻断p65的核转位。此外，白藜芦醇对IkappaBalpha蛋白的表达水平没有影响，并抑制了IkappaBalpha的降解。进一步研究表明，白藜芦醇阻断了NEMO的泛素化，并抑制了IkappaB激酶（β）介导的核因子κB激活。这些结果表明，白藜芦醇通过抑制核因子κB和IkappaB激酶的活性有效地抑制了核因子κB信号通路。因此，白藜芦醇可能为治疗炎症相关疾病和癌症提供一种新的方法。
