Inhibition of T-cell inflammatory cytokines, hepatocyte NF-κB signaling, and HCV infection by standardized silymarin
Inhibition of T-cell inflammatory cytokines, hepatocyte NF-κB signaling, and HCV infection by standardized silymarin
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DOI：
10.1053/j.gastro.2007.02.038
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发表时间：
2007-05-01
期刊：
影响因子：
29.4
通讯作者：
Lee, David Y. -W.
中科院分区：
文献类型：
--
作者：
Polyak, Stephen J.;Morishima, Chihiro;Lee, David Y. -W.
背景与目标：慢性丙型肝炎是一个严重的全球医学问题，需要有效的治疗。由于聚乙二醇干扰素加利巴韦林治疗的标准护理费用昂贵，具有显着的副作用，并且无法治愈约一半的感染，因此许多患者寻求补充和替代药物来改善他们的健康，例如从水飞蓟（Silybum marianum）中提取的水飞蓟素。由于草药产品标准化的可变性，水飞蓟对慢性丙型肝炎的临床益处尚未确定。方法：在当前的研究中，我们重点关注标准化水飞蓟素提取物 (MK-001) 的抗炎和抗病毒特性。结果：MK-001 抑制抗 CD3 刺激的人外周血单核细胞中肿瘤坏死因子-α 的表达以及人肝癌 Huh7 细胞中核因子 κ B 依赖性转录。此外，MK-001剂量依赖性地抑制JFH-1病毒对Huh7和Huh7.5.1细胞的感染。 MK-001 对 HCV 感染具有预防和治疗作用，与干扰素 α 联合使用时，比单独使用干扰素 α 更能抑制 HCV 复制。水飞蓟素的商业制剂也显示出抗病毒活性，尽管其效果不如 MK-001 有效。提取物的抗病毒作用部分归因于 Stat1 磷酸化的诱导，而当通过高效液相色谱对提取物进行生化分级时，表明了与干扰素无关的机制。水飞蓟宾A、水飞蓟宾B和异水飞蓟宾A、异水飞蓟宾B引发最强的抗NF-κB和抗HCV作用。这些作用与 MK-001 诱导的细胞毒性无关。结论：数据表明水飞蓟素具有抗炎和抗病毒作用，并表明基于补充和替代医学的方法可能有助于慢性丙型肝炎患者的治疗。
Background & Aims: chronic hepatitis C is a serious global medical problem necessitating effective treatment. Because standard of care with pegylated interferon plus ribavirin therapy is costly, has significant side effects, and fails to cure about half of all infections, many patients seek complementary and alternative medicine to improve their health, such as Silymarin, derived from milk thistle (Silybum marianum). Milk thistle's clinical benefits for chronic hepatitis C are unsettled due to variability in standardization of the herbal product. Methods: In the current study, we focused on the anti-inflammatory and antiviral properties of a standardized Silymarin extract (MK-001). Results : MK-001 inhibited expression of tumor necrosis factor-alpha in anti-CD3 stimulated human peripheral blood mononuclear cells and nuclear factor kappa B-dependent transcription in human hepatoma Huh7 cells. Moreover, MK-001 dose dependently inhibited infection of Huh7 and Huh7.5.1 cells by JFH-1 virus. MK-001 displayed both prophylactic and therapeutic effects against HCV infection, and when combined with interferon-alpha, inhibited HCV replication more than interferon-alpha alone. Commercial preparations of Silymarin also displayed antiviral activity, although the effects were not as potent as MK-001. Antiviral effects of the extract were attributable in part to induction of Stat1 phosphorylation, while interferon-independent mechanisms were suggested when the extract was biochemically fractionated by high-performance liquid chromatography. Silybin A, silybin B, and isosilybin A, isosilybin B elicited the strongest anti-NF-kappa B and anti-HCV actions. These effects were independent of MK-001-induced cytotoxicity. Conclusions: The data indicate that Silymarin exerts anti-inflammatory and antiviral effects, and suggest that complementary and alternative medicine-based approaches may assist in the management of patients with chronic hepatitis C.