Chronic obstructive pulmonary disease (COPD) is a complex disease in which airflow obstruction is not fully reversible [1]. It is mainly characterized by airflow limitation and is defined by its character of dyspnea, cough, and sputum production, symptoms that aggravate disease severity and disease exacerbation [29]. It includes emphysema, which is characterized by airspace enlargement and destruction of lung parenchyma, and chronic bronchitis [2]. It is a chronic, progressive inflammatory condition of the small airways and lung parenchyma resulted from elevated pulmonary macrophages, neutrophils, and CD8+ T cells. Proinflammatory mediators, including IL-8, MCP-1, and IL-1β, are elevated in bronchoalveolar lavage fluid (BALF) and sputum samples obtained from patients with COPD [3-6].
Cigarette smoke is a major trigger of airways inflammation [7, 8] due to its concoction of many hundreds of toxic or otherwise bioactive substances, many of which may act in synergy [9]. Cigarette smoke has been identified as the most important risk for the development of COPD [10]. Smoking is the leading risk factor for compromised lung function stemming from COPD pathogenesis [11]. The exposure to cigarette smoke (CS) is associated with emphysema. In addition to chronic lung inflammation, emphysema is known mainly for the complex pathogenesis associated with imbalance of proteolytic and antiproteolytic activites, oxidative stress, and apoptosis of lung structural cells [12].
Roflumilast is a drug which acts as a selective, long-acting inhibitor of the enzyme PDE-4. It has anti-inflammatory effects and is under development as an orally administered drug for the treatment of inflammatory conditions of the lungs such as asthma, and chronic obstructive pulmonary disease (COPD). Its’ mechanism of action is to increase cAMP levels in eosinophils, monocytes and neutrophils through selective, competitive inhibition of PDE4. This is achieved by the failure of PDE4, when inhibited, to inactivate cAMP [13]. Increased cAMP levels in these inflammatory cells reduces their activation, thereby attenuating the inflammatory response [14]. It is thought that the accumulation of cAMP within localized immune cells and lung tissue is important in preventing the pathogenesis of COPD, particularly inflammation [30].
The fruits of Viticis Fructus has long been used in China and Korea in traditional medicine, particularly for treatment of inflammation of the respiratory system. Recently, an experimental study proved the ability of Viticis Fructus to prevent airway inflammation in an asthma model to be effective [31]. Scientific evidences of its anti-nociceptive, anti-inflammatory characteristics have supported its potential for the treatment of inflammatory disease [15-17]. It contains the flavonoids artemetin, quercetagetin, 5,3’-dihydroxy-6,7,4’-trimethoxyflava- none, and casticin, of which casticin is the primary active compound, and several studies have investigated the chemical constituents of the extracts of this fruit and the molecular mechanisms responsible for its effects [18][31][32].
In the present study, I pursued to investigate the anti-inflammatory effects of Viticis Fructus in a cigarette smoke-induced pulmonary inflammation in an animal model. The data suggest that Viticis Fructus effectively attenuated cigarette smoke-induced pulmonary inflammation through inhibition of inflammatory cell infiltration, and reduction of pro-inflammatory cytokine secretion in lung.