Therapeutic effects and mechanisms of paeonol on cigarette smoke‐induced lung inflammation (869.13)

Abstract

Cigarette smoke (CS) is known to cause persistent lung inflammation mainly regulated by redox‐sensitive pathways. Indeed, several investigations from our laboratory reveal that CS can sequentially increased intracellular ROS, activated AMP‐activated protein kinase (AMPK), mitogen‐activated protein kinases (MAPKs) and NF‐κB, increased IL‐8 production in lung cells and finally produced lung inflammation,. Thus, therapeutic targeting of oxidative stress with antioxidants is recognized to be beneficial in the treatment of CS‐induced lung inflammation COPD. Paeonol, a major component of Mu Dan Pi (Paeonia moutan), has been suggested to be a potential antioxidant and anti‐inflammatory drug against diseases in several organs. However, whether paeonol may decrease the CS‐induced oxidative stress and lung inflammation is unknown and what therapeutic mechanisms of this benefit are still unclear. In this study, we investigated the therapeutic effects and mechanisms of on CS‐induced lung inflammation. Using human bronchial epithelial cells (HBECs) received challenge by cigarette smoke extract (CSE) demonstrate the suppressive effects of paeonol on the CSE‐induced increase in intracellular ROS, activation of the AMPK/MAPKs/NF‐κB signaling pathway, and the subsequent induction of IL‐8 chemokine. Using a murine model chronic CS exposure for 4 weeks increased macrophage inflammatory protein 2, and induced lung inflammation. These CS‐induced events were alleviated by treatment with paeonol. Our results suggest a novel role for paeonol in suppressing the CSE‐induced IL‐8 in vitro via its antioxidant function and by inhibiting both ROS‐sensitive AMPK/MAPK signaling pathway and the downstream transcriptional factors NF‐κB and in improving lung inflammation induced by chronic CS exposure in vivo.