1. Vinpocetine alleviated alveolar epithelial cells injury in experimental pulmonary fibrosis by targeting PPAR-γ/NLRP3/NF-κB and TGF-β1/Smad2/3 pathways.
- Author
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Hussein ZA, Abu-Raghif AR, Tahseen NJ, Rashed KA, Shaker NS, and Fawzi HA
- Subjects
- Animals, Humans, Male, Mice, Bleomycin adverse effects, Cell Line, Disease Models, Animal, Mice, Inbred BALB C, NF-kappa B metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Oxidative Stress drug effects, PPAR gamma metabolism, Smad2 Protein metabolism, Smad3 Protein metabolism, Transforming Growth Factor beta1 metabolism, Alveolar Epithelial Cells drug effects, Alveolar Epithelial Cells metabolism, Alveolar Epithelial Cells pathology, Pulmonary Fibrosis metabolism, Pulmonary Fibrosis drug therapy, Pulmonary Fibrosis pathology, Pulmonary Fibrosis chemically induced, Signal Transduction drug effects, Vinca Alkaloids pharmacology
- Abstract
This study aimed to investigate the potential anti-fibrotic activity of vinpocetine in an experimental model of pulmonary fibrosis by bleomycin and in the MRC-5 cell line. Pulmonary fibrosis was induced in BALB/c mice by oropharyngeal aspiration of a single dose of bleomycin (5 mg/kg). The remaining induced animals received a daily dose of pirfenidone (as a standard anti-fibrotic drug) (300 mg/kg/PO) and vinpocetine (20 mg/kg/PO) on day 7 of the induction till the end of the experiment (day 21). The results of the experiment revealed that vinpocetine managed to alleviate the fibrotic endpoints by statistically improving (P ≤ 0.05) the weight index, histopathological score, reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. It also alleviated tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators significantly elevated in bleomycin-only induced animals (P ≤ 0.05). Vinpocetine managed to express a remarkable attenuating effect in pulmonary fibrosis both in vivo and in vitro either directly by interfering with the classical TGF-β1/Smad2/3 signaling pathway or indirectly by upregulating the expression of Nrf2 enhancing the antioxidant system, activating PPAR-γ and downregulating the NLRP3/NF-κB pathway making it a candidate for further clinical investigation in cases of pulmonary fibrosis., (© 2024. The Author(s).)
- Published
- 2024
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