Myricetin Alleviates Silica-Mediated Lung Fibrosis via PPARγ–PGC-1α Loop and Suppressing Mitochondrial Senescence in Epithelial Cells

作者：Weixi Xie, Lang Deng, Xiaohua Zhang, Xiaoting Huang, Jinfeng Ding, Wei Liu, Siyuan Tang · 发表于：Journal of Agricultural and Food Chemistry · 年份：2024 · DOI：10.1021/acs.jafc.4c04887 · 被引用次数：17 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Autophagy in Disease and Therapy、Lung Cancer Treatments and Mutations

OBJECTIVE: Long-term inhalation of silica dust particles leads to lung tissue fibrosis, resulting in impaired gas exchange and increased mortality. Silica inhalation triggers the aging of epithelial cells (AECs), which is a key contributor to the development of pulmonary fibrosis. Myricetin, a flavonoid compound extracted from Myrica genus plants, possesses various biological activities, including antioxidant and immunomodulatory effects. However, the mechanisms underlying myricetin's ability to counter senescence and fibrosis need to be further studied. EXPERIMENTAL APPROACH: In vivo, the antifibrotic and anti-senescence effects of myricetin were evaluated using a silica-induced pulmonary fibrosis mouse model. To further elucidate the mechanisms by which myricetin counteracts silica-induced senescence, in vitro experiments were conducted using AECs. RESULTS: Our studies revealed that myricetin treatment alleviated silica-induced mortality, improved lung function, and reduced the severity of pulmonary fibrosis in mice. Immunofluorescence analysis suggests its potential in mitigating senescence of AECs. Under laboratory conditions, myricetin intervened in the cellular senescence pathway induced by silica dust by modulating mitochondrial function. It acted through the PPARγ-PGC1α axis, effectively reducing silica-induced mitochondrial oxidative stress in AECs, promoting mitophagy, and maintaining mitochondrial dynamics. However, the efficacy of myricetin was reversed under PPAR...