Cortex Mori Radicis Mitigates Inflammation and Fibrosis in Pulmonary Fibrosis Through PI3K/AKT Pathway Suppression.

Abstract

Early in the pathogenesis of pulmonary fibrosis (PF), there are multiple inflammatory cell infiltrations in the damaged lung tissue. When lung injury persists, inflammatory cytokines prompt local fibroblasts migration and hyperproliferation, triggering abnormal deposition of extracellular matrix in the lung interstitium. This excessive repair leads to interstitial cell reorganization, triggering lung tissue fibrosis and further activation of inflammatory cells. Therefore, modulation of inflammatory mediators is of great significance in the treatment and prevention in the process of fibrosis. Cortex Mori Radicis (CMR) is a traditional Chinese herb with anti-inflammatory and antifibrotic properties. In this study, we investigated the therapeutic effects of CMR on bleomycin-induced PF using in vivo and in vitro models. In vivo experiments showed that CMR treatment significantly reduced inflammation, attenuated fibrosis, and alleviated lung function decline. In vitro, CMR inhibited migration, proliferation, and epithelial-mesenchymal transition (EMT) in A549 lung epithelial cells. Network pharmacological analysis identified 25 bioactive components and 10 key therapeutic targets in CMR, with the PI3K/AKT signaling pathway emerging as the core regulatory mechanism. Subsequent in vivo validation confirmed that CMR could inhibit the activation of the PI3K/AKT pathway. In conclusion, CMR exerts protective effects against PF by modulating the PI3K/AKT pathway, thereby attenuating inflammation and fibrotic remodeling. This study provides both pharmacodynamic evidence and mechanistic insight supporting the clinical potential of CMR and underscores the advantages of multitargeted intervention strategies offered by traditional Chinese medicine in the treatment of PF.