Dietary intake of glucoraphanin prevents the reduction of dopamine transporter in the mouse striatum after repeated administration of MPTP.

AIMS: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Although diet may influence the development of PD, the precise mechanisms underlying relationship between diet and PD pathology are unknown. Here, we examined whether dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane in cruciferous vegetables, can affect the reduction of dopamine transporter (DAT) in the mouse striatum after repeated administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). METHODS: Normal food pellet or 0.1% GF food pellet was given into male mice for 28 days from 8-week-old. Subsequently, saline (5 mL/kg × 3, 2-hour interval) or MPTP (10 mg/kg × 3, 2-hour interval) was injected into mice. Immunohistochemistry of DAT in the striatum was performed 7 days after MPTP injection. RESULTS: Repeated injections of MPTP significantly decreased the density of DAT-immunoreactivity in the mouse striatum. In contrast, dietary intake of 0.1% GF food pellet significantly protected against MPTP-induced reduction of DAT-immunoreactivity in the striatum. CONCLUSION: This study suggests that dietary intake of GF food pellet could prevent MPTP-induced dopaminergic neurotoxicity in the striatum of adult mice. Therefore, dietary intake of GF-rich cruciferous vegetables may have beneficial effects on prevention for development of PD.

Protective role of (RS )-glucoraphanin bioactivated with myrosinase in an experimental model of multiple sclerosis.

AIM: The discovery of new natural compounds with pharmacological properties is a field of interest widely growing. Recent literature shows that Brassica vegetables (Cruciferae) possess therapeutic effects particularly ascribed due to their content in glucosinolates, which upon myrosinase hydrolysis release the corresponding isothiocyanates. This study examines the potential neuroprotective and immunomodulatory effects of (RS )-glucoraphanin from Tuscan black kale (Brassica oleracea L. var. acephala sabellica) bioactivated with myrosinase (bioactive RS -GRA) (10 mg/kg/day intraperitoneally), in an experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. METHODS: EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG35-55 ) in mice. After immunization, mice were observed daily for signs of EAE and weight loss. Clinical score was evaluated using a standardized scoring system. RESULTS: By Western blot analysis of spinal cord tissues, we have demonstrated that treatment with bioactive RS -GRA significantly decreased nuclear factor (NF)-kB translocation, pro-inflammatory cytokine production such as interleukin-1ß (IL-1ß), and apoptosis (Bax and caspase 3 expression). CONCLUSION: Our results clearly demonstrate that bioactive RS -GRA treatment may represent a useful therapeutic perspective in the treatment of this disease.

Production of the cancer-preventive glucoraphanin in tobacco.

Epidemiological studies have demonstrated reduced risk of developing cancer upon consumption of diets rich in cruciferous vegetables. This chemoprevention has been largely attributed to the presence of the natural products glucosinolates, particularly the methionine-derived glucoraphanin from broccoli. Improved nutrition by functional foods or health-promoting dietary supplements is an attractive means for prevention of lifestyle-based diseases. Towards this goal, we have engineered the glucoraphanin pathway into tobacco. First, we engineered elongation of the side chain of methionine to produce the key intermediate dihomo-methionine. This process is catalyzed through two cycles in a chain-elongation pathway that takes place partly in the cytosol and partly in the chloroplast. Second, by coupling the five enzymes of the chain-elongation pathway to eight enzymes of the glucosinolate pathway, we show production of glucoraphanin together with other glucosinolates derived from chain-elongated isoleucine and/or leucine. The conversion of methionine to glucoraphanin is obtained via 14 intermediates. Demonstrating the production of the high-value glucoraphanin in a heterologous host has great potential in the food and medicinal industry as a means to generate a stable, rich source of glucoraphanin for the benefit of human health.