An article published online on October 17, 2011 in the Journal of Clinical Investigation revealed that sulforaphane, a compound that occurs in broccoli and other cruciferous vegetables, improves sensitivity to corticosteroid drugs used to treat chronic obstructive pulmonary disease (COPD), a condition that is mainly the result of smoking, characterized by chronic bronchitis and emphysema. The disease is currently treated with corticosteroids, however, the drugs only reduce symptoms by approximately 20 percent.
Individuals diagnosed with COPD experience a reduction in their lungs of histone deacetylase 2 (HDAC2), a substance that is essential to the anti-inflammatory pathway initiated by steroid drugs. In the current research, a team from Johns Hopkins University discovered that S-nitrosylation of HCAC2 due to cigarette smoke exposure resulted in HDAC2 dysfunction in lung macrophages derived from individuals with COPD. "This study provides the mechanism of exaggerated inflammation observed in COPD patients during exacerbations, which has been a barrier to developing effective therapy," stated coauthor Rajesh Thimmulappa, PhD, who is an assistant scientist at Johns Hopkins Bloomberg School of Public Health's Department of Environmental Health Sciences.
It was further discovered that sulforaphane denitrosylates HDAC2, which restored corticosteroid sensitivity. In previous research, the team demonstrated that sulforaphane activates a pathway known as Nrf2. "Restoring corticosteroid sensitivity in patients with COPD by targeting the Nrf2 pathway holds promise for effectively treating exacerbations," noted senior author Shyam Biswal, PhD, who is a professor at the Bloomberg School's Department of Environmental Health Sciences and Division of Pulmonary and Critical Care Medicine.
"Nrf2 activators such as sulforaphane can counteract oxidative and nitrosative stress and mediate glutathione-dependent denitrosylation, thereby restoring HDAC2 activity," the authors write. "The small-molecule Nrf2 activator sulforaphane may be useful as an adjuvant therapy to augment the antiinflammatory effects of glucocorticosteroids in COPD and other inflammatory diseases."
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