Trigonelline mitigates bleomycin-induced idiopathic pulmonary fibrosis in mice

Abstract

Objective: To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis (IPF) and to explore its underlying mechanisms using network pharmacology. Methods: IPF was induced in C57BL/6 mice by a single intratracheal instillation of bleomycin (5 mg/kg). Trigonelline was administered at doses of 25, 50, and 100 mg/kg/day orally from the 2nd day post-bleomycin induction up to the 14th day. In IPF-induced mice, lung coefficient, immune cell infiltration in bronchoalveolar lavage fluid, and oxidative stress were measured. Histological alterations in lung tissues were also assessed. Moreover, network pharmacology approach was conducted to reveal molecular interactions of bleomycin and trigonelline with targets of IPF. Results: Trigonelline treatment reduced bleomycin-induced oxidative stress and immune cell infiltration, and mitigated physiological changes in the lung tissues of mice. Moreover, trigonelline alleviated bleomycin-induced histological alterations in lung tissues. Network pharmacology analysis showed that bleomycin and trigonelline interacted with IPF targets, such as NFKB1, HDAC2, HIF1A, and TLR4. Conclusions: The interaction of trigonelline with key IPF targets and its ameliorative effects on lung damage and oxidative stress highlight its potential in treating IPF. It may be considered an antifibrotic agent for further clinical development.

Keywords

Trigonelline / Idiopathic pulmonary fibrosis / Antifibrotic / Bleomycin / Network pharmacology

Conflict of interest statement

The authors declare no conflict of interest.

Funding

This study received no extramural funding.

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

SG performed literature searches, conducted experiments, data acquisition, statistical analysis, and manuscript preparation. CG and GM assisted in study design and performed data and statistical analysis, and manuscript review. VSP and HMP contributed to network pharmacology, prepared figures, and manuscript revision and drafting. SK, BD, BB, and CNK assisted in preparing the first manuscript draft and executed a literature search. CRP designed the concept and study, literature search, supervised experimental studies, data, and statistical analysis, manuscript preparation, editing, and review. All authors have read, contributed to, and approved the final version of manuscript.

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