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

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. - Highlights: • Silibinin (SbN) and Legalon-SIL (SIL) are cytoprotective mixtures of natural products. • SbN and SIL reduce T cell oxidative phosphorylation and glycolysis in vitro. • SIL but not SbN blocks entry of multiple HIV isolates into T cells in vitro. • SIL's suppression of HIVmore » appears independent of its effects on T cell metabolism. • Metabolic effects of SIL and SbN may be relevant in inflammatory diseases.« less
Authors:
 [1] ;  [2] ;  [3] ;  [1] ;  [4]
  1. Department of Laboratory Medicine, University of Washington, Seattle, WA (United States)
  2. Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
  3. Department of Medicine (Division of Metabolism, Endocrinology, and Nutrition), University of Washington, Seattle, WA (United States)
  4. (United States)
Publication Date:
OSTI Identifier:
22435008
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 449; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADSORPTION; AIDS VIRUS; ATP; BLOOD; DISEASES; GLUCOSE; GLYCOLYSIS; IN VITRO; INFLAMMATION; INHIBITION; MILK; MITOCHONDRIA; MIXTURES; PHOSPHORYLATION; PLANT GROWTH; RESPIRATION; UPTAKE; WATER