Ameliorative effect of Nano berberine in bleomycin- induced lung fibrosis in male rats

Pulmonary fibrosis is a progressive and fatal lung disease characterized by excessive extracellular matrix deposition. Bleomycin (BLM)-induced pulmonary fibrosis is a widely used experimental model that replicates key pathological features of the human disease. Berberine (Brb), a natural phytochemical, exhibits anti-inflammatory and immunomodulatory properties. However, its clinical application is restricted by poor bioavailability. Nano-formulation of Brb (Nano-Brb) may enhance its therapeutic potential. Therefore, this study aimed to evaluate the protective effects of Nano-Brb against BLM-induced pulmonary fibrosis in rats and to elucidate the underlying biochemical, histopathological, immunohistochemical, and molecular mechanisms. Thirty adult male albino rats were randomly assigned into six groups: control, Brb-treated (100 mg/kg body weight), Nano-Brb-treated (100 mg/kg body weight), BLM-treated (single intratracheal dose of 5 mg/kg body weight), BLM + Brb, and BLM + Nano-Brb. Nano-Brb significantly attenuated BLM-induced pulmonary fibrosis, as evidenced by reduced pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-13 (IL-13), and tumor necrosis factor-alpha (TNF-α), as well as decreased matrix metalloproteinases (MMPs). It also modulated nuclear factor kappa B (NF-κB) and transforming growth factor-beta (TGF-β) signaling and reduced collagen type I (Col-I) and collagen type III (Col-III), connective tissue growth factor (CTGF), and neutrophil elastase (NE). Histopathological, histochemical, and immunohistochemical investigations confirmed marked improvement in lung architecture. Furthermore, Nano-Brb reduced transforming growth factor-beta 1 (TGF-β1) expression and upregulated pulmonary sirtuin 3 (SIRT3) gene expression. The present results suggest that Nano-Brb enhanced the lung’s architecture and functional performance by modulating inflammatory cytokines, oxidative stress, gene expression, and histopathological damage.

Created in https://BioRender.com. Schematic representation of the experimental design: rats were administered bleomycin to induce pulmonary fibrosis, followed by treatment with berberine or nano-berberine. The study assessed oxidative stress markers, inflammatory cytokines, histopathological and immunohistochemical changes, and gene expression related to fibrosis and inflammation. The nano-formulation demonstrated superior therapeutic efficacy.