Crocin-I mitigates diquat-induced pulmonary fibrosis via activation of the SIRT3/FOXO3a pathway

Background: Diquat (DQ) is a potent Herbicide known for its significant toxicity to humans and Animals, often resulting in severe pulmonary fibrosis, a serious and potentially life-threatening complication of DQ poisoning. Currently, there are no effective pharmacological treatments for this condition. Crocin-I, a primary bioactive component derived from crocin, possesses notable antioxidant and anti-inflammatory properties; however, its potential to inhibit DQ-induced pulmonary fibrosis has not been fully explored. This study aimed to elucidate the underlying mechanisms and therapeutic effects of crocin-I on DQ-induced pulmonary fibrosis.

Methods: C57BL/6 mice exposed to DQ served as a model of pulmonary fibrosis. Pathological characteristics were assessed with hematoxylin and eosin staining, and Collagen deposition was measured using Masson's trichrome staining. The expression of epithelial-mesenchymal transition markers was measured using Western blotting and quantitative real-time polymerase chain reaction. Additionally, proteins associated with the SIRT3/FOXO3a signaling pathway were analyzed through Western blotting and quantitative real-time polymerase chain reaction.

Results: Administration of crocin-I at a dosage of 40 mg/kg significantly reduced pulmonary fibrosis, as indicated by decreased Collagen deposition. Furthermore, treatment with crocin-I enhanced the expression of SIRT3 and FOXO3a, leading to altered levels of EMT-associated markers, specifically decreased E-cadherin and increased vimentin and α-SMA.

Conclusion: These findings suggest that crocin-I activates the SIRT3/FOXO3a pathway and alleviates DQ-induced pulmonary fibrosis, highlighting its potential as a therapeutic agent for lung injury and paving the way for further research into its clinical applications.

Crocin-I; Diquat; Diquat poisoning; Pulmonary fibrosis; SIRT3.