Protective effects of E-CG-01 (3,4-lacto cycloastragenol) against bleomycin-induced lung fibrosis in C57BL/6 mice

Idiopathic pulmonary fibrosis is an aging-related, chronic lung disease, with unclear pathogenesis and no effective treatment. One of the triggering factors in cell aging is oxidative stress and it is known to have a role in idiopathic pulmonary fibrosis. In this paper, the protective effect of the E-CG-01 (3,4-lacto-cycloastragenol) molecule in terms of its antioxidant properties was evaluated in the bleomycin induced mice lung fibrosis model. Bleomycin sulfate was administered as a single dose (2.5 U/kg body weight) intratracheally to induce lung fibrosis. E-CG-01 was administered intraperitoneally in three different doses (2 mg/kg/day, 6 mg/kg/day, and 10 mg/kg/day) for 14 days, starting three days before the bleomycin administration. Fibrosis was examined by Hematoxylin-Eosin, Masson Trichrome, and immunohistochemical staining for TGF-beta1, Type I collagen Ki-67, and gama-H2AX markers. Activity analysis of catalase and Superoxide dismutase enzymes, measurement of total oxidant, total glutathione, and Malondialdehyde levels. In histological analysis, it was determined that all three different doses of the molecule provided a prophylactic effect against the progression of fibrosis compared to the bleomycin control group. However, it was observed that only the molecule applied in the high dose decreased the total oxidant stress level. Lung weight ratio increased in the BLM group but significantly reduced with high-dose E-CG-01. E-CG-01 at all doses reduced collagen deposition, TGF-β expression, and Ki-67 expression compared to the BLM group. Intermediate and high doses of E-CG-01 also significantly reduced alveolar wall thickness and edema formation. These findings suggest that E-CG-01 has potential therapeutic effects in mitigating lung fibrosis through its antioxidant properties. •E-CG-01, a cycloastragenol derivative, showed significant prophylactic effects against bleomycin-induced lung fibrosis.•reducing alveolar wall thickening, edema and collagen deposition. The efficacy of E-CG-01 was dose-dependent; higher doses were more effective in reducing fibrosis markers and improving lung histology compared to lower doses.•E-CG-01 significantly reduced total oxidant stress (TOS) levels, indicating its important role in attenuating lung fibrosis through its antioxidant properties.•Immunohistochemical analysis revealed that E-CG-01 reduced key fibrosis markers, including TGF-beta1 and type I collagen, suggesting its potential to modulate fibrosis pathways.