During the last twenty years, new anti-inflammatory drugs are being discovered and developed as anti-cytokine agents with the massive expansion of the study on inflammatory response [1,2]. People, however, still long for cheaper and more effective alternative approaches to treat inflammation. Medicinal herbs have been used for treating inflammation related diseases, and they are often used to develop new medications [3–6]. It has been shown in a previous study that Fruit of Vitex trifolia subsp. litoralis Steenis, Viticis Fructus (VF), has anti-inflammatory properties, which occur via inhibition of the inflammatory cytokines and the mitogen-activated protein kinase (MAPK)-signaling pathway . VF is widely used in China and Korea for the treatment of pain, cold, headache, migraine, sore eyes, myalgia, and gastrointestinal infections such as bacterial dysentery and diarrhea [7–9]. In one of our recent study, VF extract prevented the development of airway remodeling in asthma . Therefore, we attempted to isolate the active compound from VF. After several rounds of activity-guided fractionations, pyranopyran-1,8-dione (PPY) was isolated (Figure 1) . We previously reported that PPY inhibits inflammation in the ovalbumin-sensitized asthma mouse model . Here, we used the CS-exposed mouse model for better understanding of the biomedical benefits of PPY, a natural chemical isolated from VF, on lung inflammation. In this study, we provide the evidence of PPY as a potent protective agent on lung inflammation.