Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2012;7(7):e41832. doi: 10.1371/journal.pone.0041832. Epub 2012 Jul 25.
Purified silymarin-derived natural products from the milk thistle plant (Silybum marianum) block hepatitis C virus (HCV) infection and inhibit T cell proliferation in vitro. An intravenous formulation of silibinin (SIL), a major component of silymarin, displays anti-HCV effects in humans and also inhibits T-cell proliferation in vitro. We show that SIL inhibited replication of HIV-1 in TZM-bl cells, PBMCs, and CEM cells in vitro. SIL suppression of HIV-1 coincided with dose-dependent reductions in actively proliferating CD19+, CD4+, and CD8+ cells, resulting in fewer CD4+ T cells expressing the HIV-1 co-receptors CXCR4 and CCR5. SIL inhibition of T-cell growth was not due to cytotoxicity measured by cell cycle arrest, apoptosis, or necrosis. SIL also blocked induction of the activation markers CD38, HLA-DR, Ki67, and CCR5 on CD4+ T cells. The data suggest that SIL attenuated cellular functions involved in T-cell activation, proliferation, and HIV-1 infection. Silymarin-derived compounds provide cytoprotection by suppressing virus infection, immune activation, and inflammation, and as such may be relevant for both HIV mono-infected and HIV/HCV co-infected subjects.
水飞蓟素衍生的天然产物可从奶蓟草植物（水飞蓟）中提取，能阻止丙型肝炎病毒（HCV）感染并抑制体外 T 细胞增殖。水飞蓟宾（SIL）是水飞蓟素的主要成分，其静脉制剂在人体内具有抗 HCV 作用，在体外也能抑制 T 细胞增殖。我们发现 SIL 可抑制 TZM-bl 细胞、PBMC 和 CEM 细胞中的 HIV-1 复制。SIL 对 HIV-1 的抑制作用与主动增殖的 CD19+、CD4+和 CD8+细胞的剂量依赖性减少一致，导致表达 HIV-1 共受体 CXCR4 和 CCR5 的 CD4+T 细胞减少。SIL 抑制 T 细胞生长不是由于细胞周期停滞、凋亡或坏死引起的细胞毒性。SIL 还可阻断 CD4+T 细胞上激活标记物 CD38、HLA-DR、Ki67 和 CCR5 的诱导。数据表明，SIL 减弱了与 T 细胞激活、增殖和 HIV-1 感染相关的细胞功能。水飞蓟素衍生的化合物通过抑制病毒感染、免疫激活和炎症提供细胞保护，因此可能与 HIV 单一感染和 HIV/HCV 共感染患者均相关。
