Magnolol alleviates inflammation and oxidative stress in COPD via MAPK and Nrf2 signaling pathways

Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic and progressive lung disease which is closely related to inflammation and oxidative-stress. Magnolol (MAG) is a polyphenolic compound that possesses extensive pharmacological actions, including anti-inflammatory and anti-oxidative activities. However, the therapeutic role of MAG in COPD remains unclear. This study aimed to explore the effect and underlying mechanism of MAG in COPD using lipopolysaccharide (LPS) and cigarette smoke (CS)-induced rats model, LPS-induced RAW264.7 cells, and CS extract (CSE)-induced epithelial BEAS-2B cells. Here, MAG significantly alleviated the symptoms and lung pathological changes of COPD rats by regulating the inflammatory response and oxidative stress. Moreover, it attenuated inflammation by suppressing the production of pro-inflammatory cytokines (NO, IL-6, IL-1β, and TNF-α) in LPS-induced RAW264.7 cells, and relieved CSE-induced oxidative stress by reducing ROS accumulation and increasing the levels of antioxidant enzymes (SOD, HO-1, and NQO1) in BEAS-2B cells. Mechanistically, MAG inhibited MAPK signaling pathway via down-regulating the phosphorylation level of p38, ERK1/2 and JNK, and activated Nrf2 signaling pathway via promoting Nrf2 nucleus translocation and subsequently up-regulating the protein expressions of HO-1, NQO1, and Keap1 in vitro and in vivo. Collectively, these findings demonstrated that MAG may be a promising candidate for COPD treatment.

Keywords

• COPD
• Magnolol
• Inflammation
• Oxidative stress
• MAPK signaling pathway
• Nrf2 signaling pathway