Inhibition of HIV by Legalon-SIL is independent of its effect on cellular metabolism

Virology. 2014 Jan 20;449:96-103. doi: 10.1016/j.virol.2013.11.003. Epub 2013 Nov 27.

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.

Keywords: HIV; Metabolism; Silibinin; Silymarin; T cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Biological Transport / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism*
  • Down-Regulation / drug effects
  • Glucose / metabolism
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Milk Thistle / chemistry*
  • Plant Extracts / pharmacology*
  • Silybin
  • Silymarin / pharmacology*
  • Virus Replication / drug effects

Substances

  • Plant Extracts
  • Silymarin
  • Silybin
  • Adenosine Triphosphate
  • Glucose