Dietary polyphenols have antioxidant and antiinflammatory properties that may explain their beneficial effects (Arts and Hollman 2005
). Curcumin is an active principle of the perennial herb Curcuma longa
(commonly known as turmeric). Turmeric has a long traditional use in the Orient for many ailments, particularly as an antiinflammatory agent. Recent studies have reported that curcumin inhibits NF-κ B expression/activation, IL-8 release, cyclo-oxygenase (COX)-2, heme oxygenase-1, cytokines, and neutrophil recruitment in the lungs (Shishodia et al 2003
; Biswas et al 2005
). Curcumin has multiple properties to protect against cigarette smoke-mediated oxidative stress (Shishodia et al 2003
). It acts as oxygen radical and hydroxyl radical scavenger, increases antioxidant glutathione levels by induction of GCL, and acts as an antiinflammatory agent through inhibition of NF-κ B and IL-8 release in lung cells. Resveratrol, a flavonoid found in red wine, is an effective inhibitor of inflammatory cytokine release from macrophages in COPD patients (Culpitt, Rogers, Fenwick, et al 2003
). This antiinflammatory property of resveratrol may be due to its ability to induce sirtuins and HDAC activity (Howitz et al 2003
). A recent in vivo study has shown that resveratrol inhibits inflammatory cytokine expression in response to lipopolysaccharide in rat lungs (Birrell et al 2005
). The molecular mechanisms of antiinflammatory properties of dietary polyphenols against cigarette smoke/ oxidative stress have not yet been studied. This compound may induce phase II detoxifying genes by Nrf-2-dependent mechanisms.
Recent studies from our laboratory show that these dietary polyphenols restore glucocorticoid functions in response to oxidative stress imposed by cigarette smoke by up-regulation of HDAC activity in the monocyte/ macrophage (U937) and MonoMac6 cell lines (Rahman et al 2005
). This was associated with restoration of HDAC1, HDAC2, and HDAC3 levels, suggesting that dietary polyphenol-mediated inhibition of proinflammatory cytokines increases formation of HDAC-p65 complex with glucocorticoid receptor, hence rendering NF-κ B ineffective. The other possible mechanism of polyphenol-mediated inhibition of inflammatory response is by quenching oxidants and aldehydes and inhibiting histone deacetyl-transferase activity. Catechins present in green tea (epigal-locatechin-3-gallate) in addition to theophylline may be effective in cigarette smoke-mediated oxidative stress and inflammatory response (Schwartz et al 2005
). However, this compound has never been tested in in vitro or in vivo smoking models. Overall, these dietary polyphenols and flavonols may not only act as antioxidant/antiinflammatory agents, but also possibly increase the efficacy of glucocorticoids in COPD.
Bioflavonoids possess both antioxidant and antiinflammatory properties and hence may influence chronic inflammatory diseases such as COPD. Tabak and colleagues (2001)
studied the intake of catechins, flavonols, and flavones in relation to pulmonary function and COPD symptoms in 13 651 adults from three Dutch cities. Dietary intake of catechin (eg, green tea polyphenols, epigallocatechin gallate), flavonol (eg, quercetin and kaempferol), and flavone (eg, apigenin and luteolin) was positively associated with FEV1
and inversely associated with chronic cough and breathlessness, but not chronic phlegm. More importantly, single-component (such as catechin) intake was independently associated with FEV1
and all three COPD symptoms, whereas flavonol and flavone intake was independently associated with chronic cough only. The importance of this study was further substantiated by a study by Walda and colleagues (2002)
, who showed the beneficial protective effect of fruit containing polyphenols and vitamin E against COPD symptoms in 20-year COPD mortality from three European countries, in Finnish, Italian, and Dutch cohorts. These important studies certainly encourage further multinational studies to demonstrate the beneficial effects of a high intake of nutraceuticals (polyphenols/bioflavonoids) against COPD symptoms.