Polyak Stephen J, Morishima Chihiro, Shuhart Margaret C, Wang Chia C, Liu Yanze, Lee David Y-W
Department of Laboratory Medicine, University of Washington, Seattle, Washington 98104-2499, USA.
Gastroenterology. 2007 May;132(5):1925-36. doi: 10.1053/j.gastro.2007.02.038. Epub 2007 Feb 21.
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.
In the current study, we focused on the anti-inflammatory and antiviral properties of a standardized Silymarin extract (MK-001).
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-kappaB and anti-HCV actions. These effects were independent of MK-001-induced cytotoxicity.
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.
慢性丙型肝炎是一个严重的全球性医学问题，需要有效的治疗方法。由于聚乙二醇化干扰素联合利巴韦林治疗的标准疗法成本高昂、有显著副作用且无法治愈约一半的感染病例，许多患者寻求补充和替代医学来改善健康状况，比如从水飞蓟（水飞蓟属植物）中提取的水飞蓟素。由于该草药产品标准化存在差异，水飞蓟对慢性丙型肝炎的临床益处尚未明确。
在本研究中，我们聚焦于一种标准化水飞蓟素提取物（MK - 001）的抗炎和抗病毒特性。
MK - 001抑制抗CD3刺激的人外周血单个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κB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对丙型肝炎病毒感染显示出预防和治疗作用，并且与α干扰素联合使用时，比单独使用α干扰素更能抑制丙型肝炎病毒复制。水飞蓟素的商业制剂也显示出抗病毒活性，尽管效果不如MK - 001显著。提取物的抗病毒作用部分归因于诱导信号转导和转录激活因子1磷酸化，而当通过高效液相色谱对提取物进行生化分离时，提示存在不依赖干扰素的机制。水飞蓟宾A、水飞蓟宾B、异水飞蓟宾A和异水飞蓟宾B引发最强的抗核因子κB和抗丙型肝炎病毒作用。这些作用独立于MK - 001诱导的细胞毒性。
数据表明水飞蓟素具有抗炎和抗病毒作用，并提示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管理。
