Sesquiterpene lactones from the traditional Chinese medicine Eupatorium lindleyanum DC. and their preliminary protective effects against nano-SiO₂-induced injury

Eupatorium lindleyanum DC. is a traditional Chinese medicinal plant containing sesquiterpene lactones, but its sesquiterpene lactone constituents and their biological relevance remain insufficiently characterized. In this study, sesquiterpene lactones from E. lindleyanum were systematically isolated and structurally characterized by HRESIMS, NMR spectroscopic analysis, and stereochemical methods. Selected compounds were evaluated for their protective effects in MLE-12 lung epithelial cells injured by nano-sized silicon dioxide (nano-SiO₂), and eupalinolide B was further investigated as a representative active compound in a mouse model of nano-SiO₂-induced pulmonary injury. Oxidative stress-related indicators and selected antioxidant proteins were analyzed, while molecular docking and molecular dynamics simulations were used as exploratory tools to predict possible protein–ligand interactions. As a result, 40 sesquiterpene lactones, including 20 undescribed analogues, were isolated and identified. Preliminary biological evaluation showed that several selected compounds attenuated nano-SiO₂-induced MLE-12 cell injury, among which eupalinolide B exhibited relatively prominent activity. In vivo, eupalinolide B alleviated histopathological lung damage and modulated oxidative stress-related indicators, accompanied by changes in Nrf2- and γ-GCSc-related antioxidant proteins. These findings enrich the chemical knowledge of sesquiterpene lactones from E. lindleyanum and identify eupalinolide B as a representative bioactive compound with preliminary protective effects against nano-SiO₂-induced pulmonary injury.