Protective effect of pteryxin on LPS-induced acute lung injury via modulating MAPK/NF-κB pathway and NLRP3 inflammasome activation

Ethnopharmacological relevance: Peucedanum praeruptorum seed root is a common medicinal herb with antipyretic, expectorant, antitussive, and therapeutic effects against bronchitis and furuncle. The roots of this herb contain many coumarin compounds, including pteryxin. Aim of this study: To investigate whether pteryxin can alleviate the LPS-induced lung injury and the mechanism involved. Material and methods: Male BALB/C mice were orally given sodium carboxymethylcellulose (CMC-Na) (0.5%, 1mL/100g) and pteryxin (suspended in CMC-Na; 0.5%) at 5, 10, 25 mg/kg once daily for 7 days. Subsequently, the mice received a single intratracheal instillation of 5 mg/kg LPS or saline as the control. After 8 hours, the mice were sacrificed to collect bronchoalveolar lavage fluid (BALF) and lung tissues. These samples were used to determine the lung W/D (wet/dry) weight ratio, total protein (TP) levels, inflammatory cytokines (IL-6, TNF-alpha, and IL-1 beta) and expression of protein involved in MAPK/NF-kappa B pathway and NLRP3 inflammasome. H&E staining was carried out on tissue sections to explore the pathological alterations induced by LPS. The protein expression of F4/80 and NLRP3 in lung tissues was analyzed using immunohistochemical staining. The binding of pteryxin to target proteins (MAPK, NF-kappa B and NLRP3) was determined based on molecular docking tests. Results: Treatment with pteryxin reduced the lung W/D weight ratio, total protein (TP) level and levels of inflammatory cytokines (TNF alpha, IL-6 and IL-1 beta) significantly. Therefore, it ameliorated LPS-induced inflammatory response in BALB/C mice. Moreover, pteryxin suppressed LPS-induced upregulation of proteins involved in MAPK/NF-kappa B signaling pathway and NLRP3 inflammasome activation. The expression level of F4/80 and NLRP3 was also downregulated by pteryxin pretreatment in lung tissues. Docking analysis revealed that pteryxin bound to target proteins (MAPK, NF- kappa B and NLRP3) with a fit-well pattern . Conclusion: Pteryxin may attenuate LPS-induced acute lung injury by dampening MAPK/NF-kappa B signaling and NLRP 3 inflammasome activation.