Hydrogen sulfide mediates the vasoactivity of garlic

Departments of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/2007; 104(46):17977-82. DOI: 10.1073/pnas.0705710104
Source: PubMed


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 (H(2)S), an endogenous cardioprotective vascular cell signaling molecule. This H(2)S production, measured in real time by a novel polarographic H(2)S 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. H(2)S 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 (RS(n)H), a key intermediate during the formation of H(2)S. Organic polysulfides (R-S(n)-R'; n > 2) also undergo nucleophilic substitution at a sulfur atom, yielding RS(n)H and H(2)S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H(2)S. The vasoactivity of garlic compounds is synchronous with H(2)S production, and their potency to mediate relaxation increases with H(2)S yield, strongly supporting our hypothesis that H(2)S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H(2)S can be used to standardize garlic dietary supplements.

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Available from: Scott Isbell, Apr 20, 2015
    • "3-MST generates H2S from 3-mercaptopyruvate which is itself generated by cysteine aminotransferase (CAT; (Kimura, 2010)). Red blood cells can generate H2S non-enzymatically from inorganic polysulfides, a finding which has prompted the idea that H2S may mediate the beneficial vascular effects of dietary garlic (Benavides et al., 2007). H2S is also known to be liberated in a redox-or pH-sensitive manner from sulfur 'stores'; i.e. sulfur bound to proteins in mitochondria or the cytosol (Kimura, 2010). "
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    ABSTRACT: Ion channels represent a large and growing family of target proteins regulated by gasotransmitters such as nitric oxide, carbon monoxide and, as described more recently, hydrogen sulfide. Indeed, many of the biological actions of these gases can be accounted for by their ability to modulate ion channel activity. Here, we report recent evidence that H2 S is a modulator of low voltage-activated T-type Ca(2+) channels, and discriminates between the different subtypes of T-type Ca(2+) channel in that it selectively modulates Cav3.2, whilst Cav3.1 and Cav3.3 are unaffected. At high concentrations, H2 S augments Cav3.2 currents, an observation which has led to the suggestion that H2 S exerts its pro-nociceptive effects via this channel, since Cav3.2 plays a central role in sensory nerve excitability. However, at more physiological concentrations, H2 S is seen to inhibit Cav3.2. This inhibitory action requires the presence of the redox-sensitive, extracellular region of the channel which is responsible for tonic metal ion binding, and which particularly distinguishes this channel isoform from Cav3.1 and 3.3. Further studies indicate that H2 S may act in a novel manner to alter channel activity by potentiating the zinc sensitivity / affinity of this binding site. This review discusses the different reports of H2 S modulation of T-type Ca(2+) channels, and how such varying effects may impact on nociception, given the role of this channel in sensory activity. This subject remains controversial, and future studies are required before the impact of T-type Ca(2+) channel modulation by H2 S might be exploited as a novel approach to pain management. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · The Journal of Physiology
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    • "Garlic has been used as an herbal remedy for thousands of years (Chen, Kao, Tseng, Chang, & Hsu, 2014; Kim, Kang, & Gweon, 2013; Ota et al., 2012); while its health benefits especially the cardioprotective effects have been documented in some clinical studies (Qidwai & Ashfaq, 2013; Rohner, Ried, Sobenin, Bucher, & Nordmann, 2014; Stabler, Tejani, Huynh, & Fowkes, 2012), the mechanisms remain elusive. Benavides and co-workers (Benavides et al., 2007) provided a completely new mechanism by showing that garlic extracts, as well as its major compounds diallyl trisulphide (DATS) and diallyl disulphide (DADS), could be converted into H2S by human red blood cells or by rat aorta, and the resulting H2S was able to relax rat aorta ring. Another group reported that S-allyl cysteine , the major water soluble compound of aged garlic extract, was protective against myocardial infarction through an H2S dependent mechanism (Chuah, Moore, & Zhu, 2007). "
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    ABSTRACT: Hydrogen sulphide (H2S), viewed as a deadly environmental pollutant, is now intensively researched as the third gaseous signalling molecule, ubiquitously present and with a myriad of physiological functions. We studied garlic (Allium sativum L.) scapes, the underexplored yet widely consumed “flower stalks” of garlic, for their organosulphide constituents and H2S-releasing activity. Oils obtained from pH-adjusted (pH 3.0–9.0) puree contained 15 organosulphides that showed sensitivity to the pH values of the processing media. Disulphides are significantly higher in the oil obtained at basic pH while trisulphides and cyclic organosulphides were much higher in the oils isolated at the acidic to weakly acidic pH values. A cell-based fluorescent method was used to quantify the H2S-releasing capacity, expressed as diallyl trisulphide equivalents (DATS-E in mmol DATS/g). DATS-E values significantly increased with increasing concentrations of trisulphides and tetrasulphides but showed inverse relationship with the increase in disulphides concentration. Common cooking method of stir-frying resulted in loss of more than 96% of the organosulphides and the oil obtained had an 85-fold lower DATS-E value.
    Full-text · Article · Aug 2015 · Journal of Functional Foods
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    • "There is also a wealth of evidence that the enteric flora contributes to the pathogenesis of NSAIDenteropathy , but it is unclear if the bacteria play a primary role in ulcer formation, or merely exacerbate injury once it has occurred (Uejima et al., 1996; Hagiwara et al., 2004). In the present study, we have examined the possibility that a garlic-derived H2S donor, diallyl disulphide (DADS) (Benavides et al., 2007), could prevent NSAID-induced enteropathy in a rat model. We also attempted to determine if "
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    ABSTRACT: Background and purpose: Hydrogen sulphide is an important mediator of gastrointestinal mucosal defence. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is significantly limited by their toxicity in the gastrointestinal tract. Particularly concerning is the lack of effective preventative or curative treatments for NSAID-induced intestinal damage and bleeding. We evaluated the ability of a hydrogen sulphide donor to protect against NSAID-induced enteropathy. Experimental approach: Intestinal ulceration and bleeding were induced in Wistar rats by oral administration of naproxen. The effects of suppression of endogenous hydrogen sulphide synthesis or administration of a hydrogen sulphide donor (diallyl disulphide) on naproxen-induced enteropathy was examined. Effects of diallyl disulphide on small intestinal inflammation and intestinal microbiota were also assessed. Bile collected after in vivo naproxen and diallyl disulphide administration was evaluated for cytotoxicity in vitro using cultured intestinal epithelial cells. Key results: Suppression of endogenous hydrogen sulphide synthesis by β-cyano-L-alanine exacerbated naproxen-induced enteropathy. Diallyl disulphide co-administration dose-dependently reduced the severity of naproxen-induced small intestinal damage, inflammation and bleeding. Diallyl disulphide administration attenuated naproxen-induced increases in the cytotoxicity of bile on cultured enterocytes, and prevented or reversed naproxen-induced changes in the intestinal microbiota. Conclusions and implications: Hydrogen sulphide protects against NSAID-enteropathy in rats, in part reducing the cytotoxicity of bile and preventing NSAID-induced dysbiosis.
    Full-text · Article · Oct 2014 · British Journal of Pharmacology
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