Cortex Mori Radicis mitigates pulmonary fibrosis and inflammation by suppressing the PI3K/AKT pathway

Pulmonary fibrosis (PF) is a devastating, progressive interstitial lung disease characterized by excessive extracellular matrix deposition and lung tissue remodeling, leading to severe respiratory impairment. Current treatments for pulmonary fibrosis are limited, often failing to halt disease progression or reverse established fibrosis. A key pathological event in PF is persistent inflammation, which drives fibroblast activation and hyperproliferation, ultimately triggering fibrotic remodeling. Modulating these inflammatory and fibrotic pathways is crucial for effective intervention. Cortex Mori Radicis (CMR), a traditional Chinese herb, is recognized for its anti-inflammatory and antifibrotic properties, making it a compelling candidate for investigating novel therapeutic strategies against PF.

Researchers investigated the therapeutic effects of Cortex Mori Radicis (CMR) in both in vivo and in vitro models of pulmonary fibrosis. For in vivo studies, they used a bleomycin-induced pulmonary fibrosis model (species not specified, typically rodents) to mimic the disease progression. Animals received CMR treatment (dose and route not specified in abstract) and were evaluated for inflammation, fibrosis, and lung function decline. In vitro experiments utilized A549 lung epithelial cells to assess the impact of CMR on cell migration, proliferation, and epithelial-mesenchymal transition (EMT). Network pharmacological analysis was employed to identify bioactive components and key therapeutic targets of CMR, followed by in vivo validation of the identified core regulatory mechanism.

Cortex Mori Radicis (CMR) treatment demonstrated significant protective effects against pulmonary fibrosis in both experimental models. In vivo, CMR treatment significantly reduced inflammation, attenuated fibrotic remodeling, and alleviated lung function decline. These improvements suggest a broad impact on the disease pathology. In vitro, CMR effectively inhibited the migration, proliferation, and epithelial-mesenchymal transition (EMT) of A549 lung epithelial cells, key processes contributing to fibrosis. Network pharmacological analysis identified 25 bioactive components and 10 key therapeutic targets within 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, underscoring its mechanistic role in attenuating inflammation and fibrotic remodeling.