Ganoderic acid a potential protective impact on bleomycin (BLM) -induced lung fibrosis in albino mice: Targeting caveolin 1/TGF-β/ Smad and P38MAPK signaling pathway

• Published in: Archives of biochemistry and biophysics 2025-02, Vol.764, p.110284, Article 110284
• Main Authors: Elshamy, Amira M., El Tantawy, Asmaa F., Basha, Eman H., Eltabaa, Eman F., Arakeeb, Heba M., Ahmed, Ahmed S., Abdelsattar, Amal M., Ibrahim, Rowida Raafat, El Deeb, Omnia Safwat, Eid, Asmaa M., Mashal, Shaimaa S., Safa, Mohamed A., Shalaby, Amany Mohamed, Ibrahim, Hoda A.
• Format: Article
• Language: English
• Subjects: Caveolin 1; Ganoderic acid A; Lung fibrosis; P38MAPK; Smad; TGF-β
• ISSN: 0003-9861; 1096-0384; 1096-0384
• DOI: 10.1016/j.abb.2024.110284

Bleomycin (BLM), an anticancer medication, can exacerbate pulmonary fibrosis by inducing oxidative stress and inflammation. Anti-inflammatory, anti-fibrotic, and antioxidant properties are exhibited by ganoderic acid A (GAA). So, we aim to assess GAA's protective impact on lung fibrosis induced via BLM. Forty mice were randomly classified into four groups. Lung fibrosis was induced by injection of BLM intraperitoneally (15 mg/kg body weight). GAA was given by oral gavage (25 mg/kg body weight). Lung tissue MDA, TAC, and GSH were assessed spectrophotometrically. As well, TGFβ, p38 MAPK, TNF-α, IL-1β, and CAV1 levels were measured by enzyme-linked immunosorbent assay. Gene expression of tumor growth factor beta (TGF-β), Smad2, Smad3, and glutamate-cysteine ligase (GCL) were also evaluated. GAA had significantly improved biochemical biomarkers as well as histopathology of the lung. The protective impact of GAA may be linked to the upregulation of GCL gene expression and subsequent GSH levels. In addition, the GAA-treated group showed a significant decrement in the levels of TGF-β, Smad2&3, P38 MAPK, TNF-α, IL1β, and MDA compared to BLM induced lung fibrosis group. GAA has a protective impact on lung fibrosis induced by BLM via downregulation of TGF-β and upregulation of CAV1 level and GCL expression which may play a critical role in the improvement of the pathogenesis of lung fibrosis induced via BLM. [Display omitted] •Ganoderic acid A has a Mitigative effect on BLM-induced lung fibrosis by improving antioxidants the levels, increasing CAV 1 with concomitant opposite decrement of TGF-β/Smad and MAPK.•GAA has an anti-inflammatory effect by reducing TGF-β, TNFα & IL-6.•GAA ameliorate GCL gene expression.•GAA mediates its effect via targeting the TGF-β signaling pathway.