Abstract

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease with obscure pathogenesis. Increasing evidence suggests that cellular senescence is an important mechanism underlying in IPF. Clinical treatment with drugs , such as pirfenidone and nintedanib , reduces the risk of acute exacerbation and delays the decline of pulmonary function in patients with mild to moderate pulmonary fibrosis , and with adverse reactions. Hesperidin was previously shown to alleviate pulmonary fibrosis in rats by attenuating the inflammation response. Our previous research indicated that the Citrus alkaline extracts, hesperidin as the main active ingredient, could exert anti-pulmonary fibrosis effects by inhibiting the senescence of lung fibroblasts . However, whether hesperidin could ameliorate pulmonary fibrosis by inhibiting fibroblast senescence needed further study. Purpose This work aimed to investigate whether and how hesperidin can inhibit lung fibroblast senescence and thereby alleviate pulmonary fibrosis Methods Bleomycin was used to establish a mouse model of pulmonary fibrosis and doxorubicin was used to establish a model of cellular senescence in MRC-5 cells in vitro . The therapeutic effects of hesperidin on pulmonary fibrosis using h a ematoxylin-eosin staining, Masson staining, enzyme-linked immunosorbent assay, immunohistochemistry , western blotting and quantitative Real-Time PCR. The anti-senescent effect of hesperidin in vivo and in vitro was assessed by western blotting, quantitative Real-Time PCR and senescence-associated β‐galactosidase Results We demonstrated that hesperidin could alleviate bleomycin-induced pulmonary fibrosis in mice. The expression level of senescence marker proteins p53, p21 , and p16 was were downregulated, along with the myofibroblast marker α-SMA. The number of senescence-associated β-galactosidase-positive cells was significantly reduced by hesperidin intervention i