Unravelling the potential of Vitex negundo leaf extract in LPS-induced acute lung injury in mice through modulation of the TLR-4/NF-κB p65/iNOS pathway: Insights from integrated phytochemical characterization, in silico, and in vivo analysis

Fuente: PubMed "medicinal and aromatic plants"
Tissue Cell. 2026 Mar 13;101:103470. doi: 10.1016/j.tice.2026.103470. Online ahead of print.ABSTRACTBACKGROUND: Vitex negundo L. is a traditionally used medicinal plant with documented anti-inflammatory, antioxidant, and immunomodulatory properties. Although previous studies have demonstrated its efficacy in allergic asthma, its protective potential in acute lung injury (ALI) remains unexplored. The present study aimed to investigate the effects and underlying molecular mechanism of Vitex negundo L. leaf extract (VNE) against lipopolysaccharide (LPS)-induced acute lung injury in mice model.MATERIALS AND METHODS: Phytochemical characterization of VNE was performed using High-Performance Liquid Chromatography (HPLC), Gas Chromatography-Mass Spectrometry (GC-MS), and Fourier Transform Infrared Spectroscopy (FTIR). Hematological, biochemical, histopathological, cytokine, and molecular analysis, along with in silico docking studies, were conducted to assess the protective effects of VNE on LPS-induced lung injury.RESULTS: GC-MS and FTIR confirmed the presence of diverse phytoconstituents, whereas HPLC identified agnuside as a major bioactive compound. VNE effectively mitigated LPS-induced pathological alterations and pulmonary edema. It significantly reduced WBC and lymphocyte counts, C-reactive protein, LDH, pro-inflammatory cytokines, and myeloperoxidase activity, while restoring antioxidant markers and decreasing malondialdehyde content. VNE also downregulated TLR-4 mRNA expression and reduced iNOS and NF-κB p65 protein levels, suggesting inhibition of the TLR-4/NF-κB p65/iNOS signaling pathway. Molecular docking demonstrated strong binding affinity of agnuside with TLR-4, NF-κB p65, and iNOS through hydrogen bonding and hydrophobic interactions, supporting its ability to inhibit these key inflammatory mediators.CONCLUSION: VNE exerts potent protective effects against LPS-induced ALI by modulating TLR-4/NF-κB p65/iNOS signaling pathway, validating its ethnopharmacological relevance and therapeutic potential in lung inflammatory disorders.PMID:41844019 | DOI:10.1016/j.tice.2026.103470