title: Osthole Alleviates Bleomycin-Induced Pulmonary Fibrosis via Modulating Angiotensin-Converting Enzyme 2/Angiotensin-(1-7) Axis and Decreasing Inflammation Responses in Rats.
abstract: Studies have shown that angiotensin-converting enzyme 2 (ACE2) plays modulating roles in lung pathophysiology, including pulmonary fibrosis (PF) and acute lung injury. Pulmonary fibrosis is a common complication in these interstitial lung diseases, and PF always has a poor prognosis and short survival. To date, there are few promising methods for treating PF, and they are invariably accompanied by severe side effects. Recent studies have showed that the traditional Chinese herbal extract, osthole, had beneficial effects on lipopolysaccharide (LPS) induced acute lung injury (ALI) via an ACE2 pathway. Here we further investigated the protective effects of osthole on bleomycin induced pulmonary fibrosis and attempted to determine the underlying mechanism. PF mode rats were induced by bleomycin (BLM) and then subsequently administered osthole. Histopathological analyses were employed to identify PF changes. The results showed that BLM resulted in severe PF and diffuse lung inflammation, together with significant elevation of inflammatory factors and a marked increase in expression of angiotensin II (ANG II) and transforming growth factor-beta 1 (TGF-β1). ACE2 and angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. Meanwhile, osthole treatment attenuated BLM induced PF and inflammation, decreased the expression of these inflammatory mediators, ANG II, and TGF-β1, and reversed ACE2 and ANG-(1-7) production in rat lungs. We conclude that osthole may exert beneficial effects on BLM induced PF in rats, perhaps via modulating the ACE2/ANG-(1-7) axis and inhibiting lung inflammation pathways.
authors.affiliation: Department of Radiology, Xijing Hospital, Fourth Military Medical University.
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Hao
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001761:Bleomycin; D003094:Collagen / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D016207:Cytokines; D010446:Peptide Fragments; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D000804:Angiotensin II; D003094:Collagen; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7); C046627:osthol