Inula racemosa ameliorates acute lung injury through integrated modulation of innate immune signalling, inflammation activation and redox homeostasis
Abstract
Background: Chronic respiratory diseases are associated with persistent inflammation and dysregulated immune responses. Although corticosteroids are widely used, prolonged therapy may cause immunosuppression and increase susceptibility to secondary infections. Inula racemosa (IR) Hook. F. (Pushkarmool), an Ayurvedic medicinal plant traditionally used for respiratory and inflammatory disorders, contains bioactive sesquiterpene lactones, particularly alantolactone and isoalantolactone, with reported anti-inflammatory and immunomodulatory activities. Methods: The study employed human lung epithelial NCI-H460 cells and an lipopolysaccharide (LPS) induced pulmonary inflammation model in BALB/c mice. Cytotoxicity and inflammatory responses were evaluated following treatment with IR extract. Gene expression of key inflammatory and signalling markers was analysed by RT-qPCR, while protein levels of inflammatory cytokines were quantified using ELISA. Cytokine profiling, BALF cellular analysis, and lung histopathological examination were performed to assess the anti-inflammatory effects of the extract. The expression of genes associated with the TLR4/MyD88/NF-κB, MAPK, NLRP3 inflammasome, and Nrf2/HO-1 pathways was investigated to elucidate the potential molecular mechanisms underlying observed effects. Results: IR extract attenuated LPS-induced inflammatory responses in NCI-H460 cells, with reduced production of TNF-α, IL-6, IL-1β, IL-8, IL-18, IL-4, and CCL2. In LPS-challenged BALB/c mice, treatment reduced inflammatory cell infiltration, including neutrophils, in BAL fluid and improved inflammation-associated histopathological alterations in lung tissue. Conclusions: The findings demonstrate that whole IR extract possesses significant anti-inflammatory activity in cellular and experimental pulmonary inflammation models. Its effects may involve modulation of multiple inflammatory and antioxidant signalling pathways. These findings provide experimental support for the traditional use of IR in respiratory inflammatory conditions and warrant further mechanistic and translational investigations.