Abstract
Introduction: This study aimed to reveal the potential mechanism of Ginkgo biloba extract (GBE) in alleviating pulmonary fibrosis. Methods: We examined cell viability, PTEN-induced putative kinase 1 (PINK1), Parkin, and microtubule-associated protein 1 light chain 3 (LC3) II/I ratio in paraquat (PQ)-stimulated rat alveolar epithelial type II cells (RLE-6TN) receiving GBE treatment. LC3 enrichment in mitochondria was detecting the immunofluorescence co-staining of LC3 and TOMM20. Then, epithelial-mesenchymal transition (EMT) was evaluated by α smooth muscle actin (α-SMA) and E-cadherin using immunofluorescence. Also, p-p38 and p38 were measured to evaluate p38 mitogen-activated protein kinase (MAPK) pathway using Western blot. SB203580 was used to inhibiting p38 in RLE-6TN cells. The changes in histopathological alteration, α-SMA, E-cadherin, PINK1, Parkin, LC3 II/I ratio, and collagen deposition were also investigated in rats with PQ stimulation and GBE treatment. Results: PQ caused the decrease in cell viability and E-cadherin, and the increase in LC3 enrichment, α-SMA, PINK1, Parkin, and LC3 II/I ratio (p < 0.05). p-p38 was increased after PQ stimulation (p < 0.05). In PQ-stimulated RLE-6TN cells, GBE elevated cell viability and E-cadherin and reduced LC3 enrichment, α-SMA, PINK1, Parkin, LC3 II/I ratio, and p-p38 (p < 0.05). Both of GBE and SB203580 significantly reversed PQ-induced changes abovementioned in cells. Rats with PQ stimulation developed the increase in hydroxyproline activity, α-SMA, p-p38, PINK1, Parkin LC3 II/I ratio, and the decrease in E-cadherin (p < 0.05). GBE significantly reversed PQ-induced changes abovementioned in rats. GBE mitigated inflammatory infiltrates, alveolar wall thickening, and collagen deposition in rats undergoing PQ stimulation. Conclusion: GBE significantly inhibited EMT and mitophagy in alveolar epithelial type II cells exposed to PQ via suppressing p38 MAPK pathway.
Journal Section:
Research Article
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