title: Bicyclol: a novel antihepatitis drug with hepatic heat shock protein 27/70-inducing activity and cytoprotective effects in mice.
abstract: Heat shock proteins (HSPs) are the best-known endogenous factors that protect against cell injury under various pathological conditions and that can be induced by various physical, chemical, and biological stressors. New research seeks to discover a compound that is clinically safe and can induce the accumulation of HSPs in patients. This paper reports that the oral administration of three doses of bicyclol, a novel antihepatitis drug, induced hepatic HSP27 and HSP70 expression in a time- and dose-dependent manner, and that bicyclol treatment stimulated heat shock factor 1 (HSF1) activation in mice. The inducing effects of bicyclol on HSP27, HSP70 and HSF1 were all blocked by quercetin, an inhibitor of HSP biosynthesis. The cytoprotective effect of HSP27/70 induced by bicyclol against hepatotoxicity of acetaminophen (AP) was assessed in mice. The prior administration of bicyclol markedly suppressed AP-induced liver injury as indicated by the reduction in the elevation of serum alanine aminotransferase and aspartate aminotransferase, in liver necrosis, in the release of cytochrome c and apoptosis-inducing factor from mitochondria, as well as in hepatic deoxyribonucleic acid fragmentation in mice. However, all the above actions of bicyclol against AP-induced mouse liver injuries were significantly attenuated by quercetin. This is the first report to show that bicyclol induces hepatic HSP27/70 expression via activation of HSF1 and that the cytoprotective action of bicyclol against liver injury is mediated by its induction of HSP27/70. These results provide new evidence for elucidating the mechanism of the hepatoprotective action of bicyclol in animals and patients.
authors.affiliation: Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing, China.
authors.forename: Xiu Qi
authors.initials: XQ
authors.lastname: Bao
authors.forename: Geng Tao
authors.initials: GT
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001713:Biphenyl Compounds / Q000378:metabolism* / Q000627:therapeutic use; D019610:Cytoprotection; D004268:DNA-Binding Proteins / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006505:Hepatitis / Q000188:drug therapy*; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D011794:Quercetin / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D004268:DNA-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C490017:Hsf1 protein, mouse; C486699:Hspb2 protein, mouse; D014157:Transcription Factors; C477843:bicyclol; D011794:Quercetin