title: Inhibitory effects of amines from Citrus reticulata on bleomycin-induced pulmonary fibrosis in rats.
abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease for which, thus far, there are no effective treatments. The pericarp of Citrus reticulata, as a traditional herbal drug, has been used for the clinical treatment of lung-related diseases in China for many years. In the present study, the amines from the pericarp of Citrus reticulata were isolated, and their hydrochlorides were prepared. The results of screening using cultured human embryonic lung fibroblasts (hELFs) revealed that, of the amines, 4-methoxyphenethylamine hydrochloride (designated as amine hydrochloride 1) possessed the most potent inhibitory effect. Further in vivo experiments using a rat model of bleomycin-induced pulmonary fibrosis demonstrated that the oral administration of amine hydrochloride 1 significantly lowered the hydroxyproline content in both serum and lung tissue, and alleviated pulmonary alveolitis and fibrosis. Immunohistochemical analysis revealed that amine hydrochloride 1 exerted its inhibitory effect against IPF through the downregulation of lung transforming growth factor (TGF)-β1 protein expression. Our results demonstrated that amine hydrochloride 1 prevented the development of bleomycin‑induced lung fibrosis in rats. Thus, our data suggest that the amines from the pericarp of Citrus reticulata have therapeutic potential for use in the treatment of IPF.
authors.affiliation: Department of Respiratory Medicine, The Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xian-Mei
authors.initials: XM
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210017, P.R. China.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Cao
authors.affiliation: Department of Respiratory Medicine, The Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210023, P.R. China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Li
mesh_terms: D000588:Amines / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D002681:China; D002957:Citrus / Q000737:chemistry; D004195:Disease Models, Animal; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000588:Amines; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D001761:Bleomycin