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PNAS 104 (46): 17977-17982

Copyright © 2007 by the National Academy of Sciences.

From the Cover


Hydrogen sulfide mediates the vasoactivity of garlic

Gloria A. Benavides*,{dagger}, Giuseppe L. Squadrito*,{dagger}, Robert W. Mills*, Hetal D. Patel{ddagger}, T. Scott Isbell{dagger},§, Rakesh P. Patel{dagger},§, Victor M. Darley-Usmar{dagger},§, Jeannette E. Doeller*,{dagger}, and David W. Kraus*,{dagger},{ddagger}

Departments of *Environmental Health Sciences, {ddagger}Biology, and §Pathology and {dagger}Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294

Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved September 12, 2007

Received for publication June 18, 2007.

Abstract: The consumption of garlic is inversely correlated with the progression of cardiovascular disease, although the responsible mechanisms remain unclear. Here we show that human RBCs convert garlic-derived organic polysulfides into hydrogen sulfide (H2S), an endogenous cardioprotective vascular cell signaling molecule. This H2S production, measured in real time by a novel polarographic H2S sensor, is supported by glucose-maintained cytosolic glutathione levels and is to a large extent reliant on reduced thiols in or on the RBC membrane. H2S production from organic polysulfides is facilitated by allyl substituents and by increasing numbers of tethering sulfur atoms. Allyl-substituted polysulfides undergo nucleophilic substitution at the {alpha} carbon of the allyl substituent, thereby forming a hydropolysulfide (RSnH), a key intermediate during the formation of H2S. Organic polysulfides (R-Sn-R'; n > 2) also undergo nucleophilic substitution at a sulfur atom, yielding RSnH and H2S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H2S. The vasoactivity of garlic compounds is synchronous with H2S production, and their potency to mediate relaxation increases with H2S yield, strongly supporting our hypothesis that H2S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H2S can be used to standardize garlic dietary supplements.

Key Words: Allium • aorta • polysulfides • red blood cells • vasorelaxation

Author contributions: G.A.B., G.L.S., V.M.D.-U., J.E.D., and D.W.K. designed research; G.A.B., R.W.M., H.D.P., T.S.I., and D.W.K. performed research; G.L.S., T.S.I., R.P.P., and D.W.K. contributed new reagents/analytic tools; G.A.B., G.L.S., J.E.D., and D.W.K. analyzed data; and G.A.B., G.L.S., T.S.I., R.P.P., V.M.D.-U., J.E.D., and D.W.K. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

See Commentary on page 17907.

To whom correspondence should be addressed at: Departments of Biology and Environmental Health Sciences, University of Alabama at Birmingham, Ryals 530B, 1665 University Boulevard, Birmingham, AL 35294-0022. E-mail: dwkraus{at}

© 2007 by The National Academy of Sciences of the USA

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