(1) Increases synthesis of glutathione [117]. |
This has implications for oxidative stress and detoxification as glutathione is the substrate for both pathways. Glutathione is also an antioxidant in its own right. |
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(2) Inhibits some Phase 1 detoxification enzymes that activate chemical carcinogens [118]. |
This reduces the level of toxic intermediates with carcinogenic potential. It also allows Phase 2 to “keep pace” with Phase 1 processing. |
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(3) Increases activity of Phase 2 detoxification enzymes. Sulforaphane is considered the most potent of the Phase 2 inducing substances [79]. |
As a monofunctional inducer, sulforaphane is considered to be a significant component of the anticarcinogenic action of broccoli. |
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(4) Provides significant antioxidant activity, largely due to its ability to induce glutathione synthesis. |
Glutathione is a critical factor in protecting organisms against toxicity and disease [119]. The ability of sulforaphane to upregulate glutathione synthesis is highly significant. |
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(5) Acts as a histone deacetylase inhibitor, providing DNA protection [120–122]. |
Development of histone deacetylase inhibitors is a key avenue for cancer drug research. |
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(6) Induces apoptosis, inhibits MMP-2 (metastasis), and inhibits angiogenesis and cell cycle arrest [28, 105, 123, 124] (interacts at several levels). |
Therapeutic interventions which exhibit several related actions targeting the same underlying defect are considered highly desirable. |
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(7) Limits proinflammatory effects of diesel chemicals by upregulation of Phase 2 enzymes [125]. |
Environmental pollutants are known to contribute to various lung diseases. Removal of the toxins reduces tendency to disease. |
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(8) Induces thioredoxin (Trx) as part of the ARE. |
Thioredoxin is implicated in cardioprotection by triggering several survival proteins [126]. Sulforaphane may have beneficial effects in cardiovascular disease. |
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(9) Bactericidal against Helicobacter pylori and also blocks gastric tumour formation in animals [127]. |
Helicobacter is known to contribute to development of stomach cancer. Elimination of the organism without the use of typical antimicrobial Triple Therapy could protect the colonic microflora. |
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(10) Protects dopaminergic cells from cytotoxicity and subsequent neuronal death (cell culture) [128]. |
Dopaminergic neurones are associated with Parkinson's disease. Pharmaceuticals to treat Parkinsonism are not without risk and the disease is not usually detected until more than 50% of the neurones have been lost. A chemoprotective tool could prevent premature loss. |
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(11) Increases p-53 (associated with tumour suppression) and bax protein expression, thereby enhancing cellular protection against cancer [129]. |
Sulforaphane is an attractive chemotherapeutic agent for tumours with a p53 mutation [62]. |
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(12) Limits effect of aflatoxin on liver cells [26]. |
Interventions which can offer significant protection against environmental and food-borne pollutants could prevent the consequences of these factors. Appropriate doses of sulforaphane-yielding substances are yet to be determined. |
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(13) Enhances natural killer cell activity and other markers of enhanced immune function [117]. |
The immune system is a critical part of the body's defences against inflammatory as well as infectious diseases. Most diseases benefit from enhancement to immune function. |
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(14) Suppresses NF-κB, a key regulator of inflammation [117]. NF-κB expression is downregulated by sulforaphane and as such downregulates inducible proinflammatory enzymes such as cyclooxygenase (COX-2) and NO synthase (iNOS). |
As an inhibitor of NF-κB as well as an activator of Nrf2, SF modulates many cancer-related events, including susceptibility to carcinogens, cell death, cell cycle, angiogenesis, invasion, and metastasis [117]. |
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(15) Sulforaphane is not directly antioxidant. Instead, it exhibits a weak prooxidant effect [130]. |
Because sulforaphane is not directly antioxidant but exerts its antioxidant effect primarily by induction of glutathione and other antioxidant compounds, it is considered to exhibit an indirect antioxidant effect. |
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(16) Potent inducer of HO-1 (haemoxygenase-1). |
Haemoxygenase-1 plays an important role in modulating the effects of oxidants in the lungs [131]. |