Elsholtzia Bodinieri vaniot dichloromethane extract exerts anti-inflammatory effects in acute lung injury mice by regulating the CCR1 and FLT1

Background Acute lung injury (ALI) is a disease characterized by diffuse dysfunction leading to systemic inflammation, increased vascular permeability and loss of alveolar epithelial cell function. Elsholtzia bodinieri Vaniot is a traditional folk medicinal and edible plant endowed with heat-clearing(Qingre) and detoxifying efficacies. Methods The dichloromethane fraction of E. bodinieri Vaniot extract (EBED) was isolated and evaluated for anti-inflammatory activity. Chemical profiling of EBED was performed using untargeted metabolomics. Putative target genes of EBED were predicted through bioinformatics analysis, and the anti-inflammatory effects of EBED were assessed both in vitro and in vivo using a model of acute lung injury (ALI). Mechanistic validation focused on CC chemokine receptor 1 (CCR1)- and Fms-like tyrosine kinase 1 (FLT1)-mediated downstream signaling pathways by Western blot and inflammatory mediator detection. In addition, the impact of EBED on gut microbiota composition was evaluated in ALI mice via fecal microbiome analysis, with particular attention to changes in the relative abundances of specific bacterial genera. Results EBED exerted markedly superior anti-inflammatory activity compared with other fractions. A total of 1775 chemical metabolites were identified in EBED. Bioinformatics analysis predicted that CCR1 and FLT1 serve as potential target genes for EBED to exert anti-inflammatory activity against ALI, which was subsequently validated in inflammatory pathways. In vitro and in vivo experiments collectively demonstrated that EBED mitigates inflammatory responses via modulating CCR1 and FLT1, as well as their downstream signaling cascades including CCR1/Ca 2+ , FLT1/PRKCA and FLT1/PRKD2, thereby regulating the expression of inflammatory mediators. Furthermore, EBED remodeled the gut microbiota structure in ALI mice. Specifically, the abundances of beneficial bacteria including Akkermansia, Lactobacillus, Ruminococcus and Coriobacteriaceae_UCG-002 were markedly elevated, while those of harmful bacteria such as Rikenellaceae, Tyzzerella and Paraprevotella were distinctly decreased. Conclusion In summary, the EBED demonstrates potent anti-inflammatory activity against ALI. This effect is mediated through the modulation of key target genes CCR1 and FLT1. Additionally, EBED exerts a favorable remodelling effect on the gut microbiota of ALI mice. These findings position EBED as a promising functional food ingredient and a potential therapeutic candidate for the prevention and treatment of ALI.