Astragalin Inhibits Pulmonary Inflammation in Cigarette Smoking-Induced Embolism
Abstract Objectives Thrombin generation is crucial to the regulation of hemostasis and thrombosis and is essential to the pathogenesis of cardiovascular disease and venous thrombosis. Pulmonary embolism is a blockage in one of the pulmonary arteries in your lung caused by blood clots due to risk factors including tobacco use. Astragalin (kaempferol 3-O-glucoside) is a flavonoid present in persimmon leaves and green tea seeds and exhibits diverse activities such as asthma and obstructive pulmonary disease. This study investigated that astragalin encumbered pulmonary inflammation caused by cigarette smoking-induced embolism. Methods Pulmonary embolism was evoked through exposure of BALB/c mice to cigarette smoke for 30 min, five days a week for eight weeks. Mice were orally administrated with 10 or 20 mg/kg astragalin for 8 weeks. For the in vitro studies, 10 U/ml thrombin was loaded to alveolar epithelial A549 cells in the absence and presence of 1–20 μM astragalin. Results Oral supplementation of astragalin reduced tissue factor and urokinase-type plasminogen activator elevated in cigarette smoking-exposed lungs. In addition, 1–20 μM astragalin attenuated the induction of protease activated receptor-1 known as coagulation factor II (thrombin) receptor-like-1, in 10 U/ml thrombin-loaded alveolar epithelial cells. Astragalin curtailed induction of the inflammatory mediators of cyclooxygenase-2, intercellular adhesion molecule-1 and inducible nitric oxide synthase in alveolar cells subjected to thrombin. Furthermore, astragalin inhibited inflammatory signaling entailing MAPK/ERK pathway. Conclusions Astragalin may be a potential agent alleviating pulmonary inflammation induced by cigarette smoking-induced embolism. Funding Sources This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1A6A3A01094891).