Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways

Abstract

BackgroundIt is widely recognized that deep inspiration (DI), either before methacholine (MCh) challenge (Bronchoprotection, BP) or after MCh challenge (Bronchodilation, BD) protects against this challenge in healthy individuals, but not in asthmatics. Sulforaphane, a dietary antioxidant and antiinflammatory phytochemical derived from broccoli, may affect the pulmonary bronchoconstrictor responses to MCh and the responses to DI in asthmatic patients.MethodsForty-five moderate asthmatics were administered sulforaphane (100 μmol daily for 14 days), BP, BD, lung volumes by body-plethsmography, and airway morphology by computed tomography (CT) were measured pre- and post sulforaphane consumption.ResultsSulforaphane ameliorated the bronchoconstrictor effects of MCh on FEV1 significantly (on average by 21 %; p = 0.01) in 60 % of these asthmatics. Interestingly, in 20 % of the asthmatics, sulforaphane aggravated the bronchoconstrictor effects of MCh and in a similar number was without effect, documenting the great heterogeneity of the responsiveness of these individuals to sulforaphane. Moreover, in individuals in whom the FEV1 response to MCh challenge decreased after sulforaphane administration, i.e., sulforaphane was protective, the activities of Nrf2-regulated antioxidant and anti-inflammatory genes decreased. In contrast, individuals in whom sulforaphane treatment enhanced the FEV1 response to MCh, had increased expression of the activities of these genes. High resolution CT scans disclosed that in asthmatics sulforaphane treatment resulted in a significant reduction in specific airway resistance and also increased small airway luminal area and airway trapping modestly but significantly.ConclusionThese findings suggest the potential value of blocking the bronchoconstrictor hyperresponsiveness in some types of asthmatics by phytochemicals such as sulforaphane.

Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes

“…Renal tubular secretion is suggested to play a major role in the elimination (37). Safety studies using BSE corresponding to 50 to 400 mmol SFN daily have shown that BSE is well tolerated without clinically significant adverse effects (42)(43)(44)(45).…”

A Randomized Controlled Trial of the Effect of Broccoli Sprouts on Antioxidant Gene Expression and Airway Inflammation in Asthmatics

“…In this study, there was no overall effect of daily ingestion of BSE for 14 days on airway hyper-responsiveness. A post-hoc analysis, however, indicated that BSE ameliorated the bronchoconstrictor effects of methacholine in 60% of the participants, but aggravated the effects among 20% of the participants 28 . Although the study lacked a placebo group, leaving the findings difficult to interpret, the heterogeneity of the lower airways response to BSE suggests that there are genetic factors that determine whether an individual is likely to have a therapeutic or adverse response to BSE.…”

Isothiocyanates: Translating the Power of Plants to People

“…Influenza virus-induced markers of inflammation were significantly lower in smokers after consumption of broccoli sprout homogenates [84]. In another study, daily 100 μmol SFN for 14 days was shown to improve the bronchoprotective response in asthmatics [85]. Broccoli sprout extract (dose equivalent to consumption of 100 - 200 g broccoli) was also shown to reduce the nasal allergic response to diesel exhaust particles in human subjects [86].…”