title: Inhibition of HIV by Legalon-SIL is independent of its effect on cellular metabolism.
abstract: In this report, we further characterized the effects of silibinin (SbN), derived from milk thistle extract, and Legalon-SIL (SIL), a water-soluble derivative of SbN, on T cell metabolism and HIV infection. We assessed the effects of SbN and SIL on peripheral blood mononuclear cells (PBMC) and CEM-T4 cells in terms of cellular growth, ATP content, metabolism, and HIV infection. SIL and SbN caused a rapid and reversible (upon removal) decrease in cellular ATP levels, which was associated with suppression of mitochondrial respiration and glycolysis. SbN, but not SIL inhibited glucose uptake. Exposure of T cells to SIL (but not SbN or metabolic inhibitors) during virus adsorption blocked HIV infection. Thus, both SbN and SIL rapidly perturb T cell metabolism in vitro, which may account for its anti-inflammatory and anti-proliferative effects that arise with prolonged exposure of cells. However, the metabolic effects are not involved in SIL's unique ability to block HIV entry.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA, United States.
authors.forename: Janela
authors.initials: J
authors.lastname: McClure
authors.affiliation: Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
authors.forename: Daciana H
authors.initials: DH
authors.lastname: Margineantu
authors.affiliation: Department of Medicine (Division of Metabolism, Endocrinology, and Nutrition), University of Washington, Seattle, WA, United States.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Sweet
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA, United States; Department of Global Health, University of Washington, Seattle, WA, United States. Electronic address: polyak@uw.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Polyak
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D020944:Silybum marianum / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D010936:Plant Extracts; D012838:Silymarin; D000077385:Silybin; D000255:Adenosine Triphosphate; D005947:Glucose
keywords: HIV; Metabolism; Silibinin; Silymarin; T cell