title: Silibinin inhibits HIV-1 infection by reducing cellular activation and proliferation.
abstract: 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.
authors: Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America.
authors: Janela
authors: J
authors: McClure
authors: Erica S
authors: ES
authors: Lovelace
authors: Shokrollah
authors: S
authors: Elahi
authors: Nicholas J
authors: NJ
authors: Maurice
authors: Jessica
authors: J
authors: Wagoner
authors: Joan
authors: J
authors: Dragavon
authors: John E
authors: JE
authors: Mittler
authors: Zane
authors: Z
authors: Kraft
authors: Leonidas
authors: L
authors: Stamatatos
authors: Leonidis
authors: L
authors: Stamatatos
authors: Helen
authors: H
authors: Horton
authors: Stephen C
authors: SC
authors: De Rosa
authors: Robert W
authors: RW
authors: Coombs
authors: Stephen J
authors: SJ
authors: Polyak
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D049109:Cell Proliferation / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D012838:Silymarin; D000077385:Silybin