The Anti-Pulmonary Fibrosis Code of Plant Anthocyanins-A Multi-Targeted Anti-Fibrotic Bioactive Compound by Inhibiting the NLRP3 Inflammasome.

Abstract

Pulmonary fibrosis (PF) is a fatal disease lacking effective treatments. Although anthocyanins possess pleiotropic biological activities, their potential in PF treatment remains insufficiently evaluated. This study intends to systematically assess the anti-fibrotic efficacy of selected anthocyanins and clarify their mechanisms of action.Data mining of six common anthocyanins identified three with the highest anti-fibrotic potential and their therapeutic targets. Animal studies revealed that these anthocyanins ameliorated bleomycin (BLM)-induced PF. Analysis identified 83 common core targets shared between the anthocyanin components and PF pathogenesis, primarily enriched in stimulus response and positive regulation of biological processes. Treatment with all three anthocyanins significantly reduced PF-associated mortality, inhibited weight loss, decreased lung coefficient, and lowered hydroxyproline (HYP) and malondialdehyde (MDA) levels in lung tissue. Furthermore, they suppressed mRNA expression of inflammatory cytokines IL-1β and TNF-α, promoted expression of the epithelial marker E-cadherin, reduced levels of fibrotic markers α-SMA and Collagen I, and modulated the inflammasome NLRP3-Caspase-1 axis ameliorates PF.Anthocyanins, especially anthocyanin-3-O-galactoside (C3G), improve BLM-induced PF by regulating the NLRP3-Caspase-1 inflammasome axis.