Rubiadin-1-methyl ether at 10 mg/kg reduced inflammatory cells in BALF by ~47.2% and downregulated fibrosis markers Fn1, Col1a1, and Acta2 by ~52.4%, ~30.8%, and ~44.3%, respectively.
Does Rubiadin-1-methyl ether improve bleomycin-induced pulmonary fibrosis in a mouse model?
Rubiadin-1-methyl ether attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting M2 macrophage polarization, presenting a potential novel plant-derived therapeutic candidate.
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To investigate the therapeutic effects of Rubiadin-1-methyl ether (RBM) on bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism by which it inhibits fibrosis through the modulation of macrophage polarization. A C57BL/6 mouse model of pulmonary fibrosis was established by intratracheal injection of BLM (3 mg/kg), followed by oral administration of RBM (3, 10, 30 mg/kg). Lung injury was assessed through histopathological examinations (HE and Masson staining), lung coefficient measurements, bronchoalveolar lavage fluid (BALF) inflammatory cell counts, and cytokine detection (TGF-β1, IL-6, etc.). Flow cytometry was employed to analyze M2 macrophages (F4/80⁺CD206⁺) in lung tissue, and qRT-PCR was used to measure the expression of fibrosis markers (Fn1, Col1a1, Acta2) and M2-related genes (Mrc1, Arg1, Tgfb1, Il10). RBM at 10 mg/kg exhibited the most potent therapeutic effect: it significantly ameliorated BLM-induced weight loss, reduced the elevated lung coefficient, and attenuated lung tissue pathological damage. In BALF, RBM reduced the total number of inflammatory cells by ~ 47.2%, with significant decreases in neutrophils (~ 59.4%) and lymphocytes (~ 25.6%) compared to the BLM group. Additionally, RBM downregulated the mRNA expression of fibrosis-associated genes: Fn1 (by ~ 52.4%), Col1a1 (by ~ 30.8%), and Acta2 (by ~ 44.3%). Flow cytometry analysis showed that RBM inhibited M2 macrophage polarization, reducing the proportion of F4/80⁺CD206⁺ cells from 28.4% ± 5.7% (BLM group) to 19.8% ± 1.8%. Correspondingly, the mRNA levels of M2 marker genes were significantly downregulated: Mrc1 (by ~ 48.3%), Arg1 (by ~ 46.1%), Tgfb1 (by ~ 59%), and Il10 (by ~ 38.7%). RBM also reduced the secretion of pro-inflammatory and pro-fibrotic factors in BALF: TGF-β1 (by ~ 28.7%), IL-6 (by ~ 26.5%), IL-1β (by ~ 55%), and TNF-α (by ~ 51%). RBM significantly attenuates pulmonary inflammation and collagen deposition, likely by inhibiting macrophage M2 polarization and suppressing the TGF-β1 signaling pathway, thereby offering a promising novel therapeutic strategy for pulmonary fibrosis. As a natural anthraquinone derivative isolated from widely distributed Rubiaceae plants (e.g., Rubia cordifolia), RBM exhibits favorable safety profiles and holds considerable potential as a plant-derived treatment candidate for idiopathic pulmonary fibrosis (IPF)—a devastating disease for which current approved therapies (e.g., nintedanib and pirfenidone) merely slow progression and are associated with significant adverse effects. Future studies should focus on elucidating RBM’s pharmacokinetic properties in preclinical models, confirming its antifibrotic efficacy in larger and more translational animal models, and exploring potential synergistic effects with existing antifibrotic agents to further enhance therapeutic outcomes.
Zhen et al. (Thu,) reported a other. Rubiadin-1-methyl ether at 10 mg/kg reduced inflammatory cells in BALF by ~47.2% and downregulated fibrosis markers Fn1, Col1a1, and Acta2 by ~52.4%, ~30.8%, and ~44.3%, respectively.
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