Trends in Molecular Medicine
ReviewGlucosinolates and isothiocyanates in health and disease
Section snippets
Glucosinolates and isothiocyanates
In 1831 Robiquet and Boutron [1] isolated sinalbin from the seeds of white mustard (Sinapis alba), thus introducing the first glucosinolate to the scientific community. Since then, more than 120 distinct glucosinolate (S-β-thioglucoside N-hydroxysulfate) structures (Figure 1a) have been described, with most isolated from cruciferous (Brassicaceae) plants (Box 1) [2]. In plants, glucosinolates are accompanied by, yet physically separated from, β-thioglucosidase enzymes known as myrosinases (EC
Protection against carcinogenesis: models and mechanisms
The first evidence that isothiocyanates are beneficial for human health came from investigations in the 1960s and 1970s using rodent models of chemical carcinogenesis. In a seminal publication, Wattenberg [20] concluded that ‘dietary constituents of this nature may diminish the impact of exposures to chemical carcinogenesis’. A contemporaneous epidemiological study [21] reported that the risk for cancer of the colon and the rectum is increased among individuals with low consumption of cabbage,
Cardiovascular protection
In the spontaneously hypertensive stroke-prone rat, feeding either dried broccoli sprouts or sulforaphane decreased oxidative stress in cardiovascular and kidney tissues, as demonstrated by lower protein nitrosation and increased glutathione, glutathione reductase, and glutathione peroxidase levels 47, 52. In addition, the endothelial-dependent relaxation of the aorta was improved, the number of infiltrating activated macrophages was reduced, and the blood pressure decreased. In an
Protection of the central nervous system
Similar to carcinogenesis and cardiovascular disease, oxidative stress and chronic inflammation are central to the pathogenesis of diseases of the central nervous system, and the protective effects of isothiocyanates are evident in models of nervous tissue injury and neurodegeneration. An example is the protection against light-induced damage of the retina by sulforaphane [54]. Four days after exposure to light, mice treated with sulforaphane had higher numbers of nuclei in the photoreceptor
Protection against diabetic nephropathy and neuropathy
In a mouse model of streptozotocin-induced diabetes, sulforaphane improved renal performance and minimized pathological changes in the glomerulus [71]. Motor nerve conduction velocity, blood flow, and pain behavior were also improved [72]. These very recent findings encourage the potential development of sulforaphane as a therapeutic to alleviate metabolic disorder and protect against renal damage and pain associated with diabetes.
Restoration of skin integrity
In the epidermis, sulforaphane induces the expression of genes coding for the structural proteins keratins 16 and 17 [73]. Because keratin 17 is functionally redundant to keratin 14, the sulforaphane-dependent induction of keratin 17 was evaluated as a potential strategy for reducing skin blistering in keratin 14 knockout mice, a model for the human skin blistering disease epidermolysis bullosa simplex. Three intraperitoneal injections of sulforaphane to a pregnant mouse every other day during
Protection against Helicobacter pylori infection
Sulforaphane also protects against H. pylori infections, which are strongly associated with the development of gastric cancer [74]. Sulforaphane-rich broccoli sprouts administered to mice infected with H. pylori and maintained on a high-salt diet reduced gastric bacterial colonization, attenuated mucosal inflammation, and prevented high salt-induced gastric corpus atrophy [75]. These findings prompted a placebo-controlled intervention study in which 48 subjects infected with H. pylori were
Concluding remarks and future perspectives
There is now a wealth of evidence regarding the protective effects of isothiocyanates. Induction of cytoprotective enzymes, inhibition of inflammatory processes, and modulation of signaling pathways are among the many diverse pharmacological outcomes of exposure to isothiocyanates. Unlike most small molecule pharmacological agents that affect single targets, the intracellular targets of isothiocyanates are multiple. Activation of transcription factor Nrf2 alone, a major outcome of
Acknowledgments
We apologize to all authors whose excellent work in this field has not been cited because of space limitations. We are very grateful to our colleagues for their invaluable contributions to the studies described in this review, and especially to Paul Talalay, Jed W. Fahey, Theresa A. Shapiro, Thomas W. Kensler, and Yuesheng Zhang (all from Johns Hopkins University), and to Research Councils UK, Cancer Research UK (C20953/A10270), the American Cancer Society (RSG-07-157-01-CNE), the Royal
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