title: Anti-pulmonary fibrotic activity of salvianolic acid B was screened by a novel method based on the cyto-biophysical properties.
abstract: Various methods have been used to evaluate anti-fibrotic activity of drugs. However, most of them are complicated, labor-intensive and lack of efficiency. This study was intended to develop a rapid method for anti-fibrotic drugs screening based on biophysical properties. A549 cells in vitro were stimulated with transforming growth factor-β1 (TGF-β1), and fibrogenesis was confirmed by conventional immunological assays. Meanwhile, the alterations of cyto-biophysical properties including morphology, roughness and stiffness were measured utilizing atomic force microscopy (AFM). It was found that fibrogenesis was accompanied with changes of cellular biophysical properties. TGF-β1-stimulated A549 cells became remarkably longer, rougher and stiffer than the control. Then, the effect of N-acetyl-L-cysteine (NAC) as a positive drug on ameliorating fibrogenesis in TGF-β1-stimulated A549 cells was verified respectively by immunological and biophysical markers. The result of Principal Component Analysis showed that stiffness was a leading index among all biophysical markers during fibrogenesis. Salvianolic acid B (SalB), a natural anti-oxidant, was detected by AFM to protect TGF-β1-stimulated A549 cells against stiffening. Then, SalB treatment was provided in preventive mode on a rat model of bleomycin (BLM) -induced pulmonary fibrosis. The results showed that SalB treatment significantly ameliorated BLM-induced histological alterations, blocked collagen accumulations and reduced α-SMA expression in lung tissues. All these results revealed the anti-pulmonary fibrotic activity of SalB. Detection of cyto-biophysical properties were therefore recommended as a rapid method for anti-pulmonary fibrotic drugs screening.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Hanying
authors.initials: H
authors.lastname: Xu
authors.affiliation: Shenyang Institute of Automation China Academy of Sciences, Shenyang, 110016, China.
authors.forename: Lianqing
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Jiangsu Kanion Pharmaceutical Co., Ltd., Nanjing, 222001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: lijianchun0317@sina.com.cn.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China; Jiangsu Kanion Pharmaceutical Co., Ltd., Nanjing, 222001, China. Electronic address: enlong_ma2014@hotmail.com.
authors.forename: Enlong
authors.initials: E
authors.lastname: Ma
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods; D055119:Elastic Modulus; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053630:Depsides
chemical_list: D000975:Antioxidants; D001572:Benzofurans; D001761:Bleomycin; D053773:Transforming Growth Factor beta1; C076944:salvianolic acid B; D053630:Depsides
keywords: A549 cells; Atomic force microscopy (AFM); Cyto-biophysical properties; Idiopathic pulmonary fibrosis (IPF); Salvianolic acid B (SalB); Young's modulus