title: 1,8-Cineole Ameliorates Steatosis of Pten Liver Specific KO Mice via Akt Inactivation.
abstract: Hepatocyte-specific Phosphatase and tensin homolog (Pten)-knockout (KO) mice exhibit hepatic lesions analogous to non-alcoholic steatohepatitis (NASH). 1,8-cineole is a monoterpene oxide and it has several biological effects including hepatoprotective effects. In this study we revealed that 1,8-cineole ameliorates NASH of Pten KO mice. Pten KO mice were assigned to a control group without any medication or to a 1,8-cineole group injected with 50 mg/kg i.p. twice per week for eight weeks. At eight weeks, livers from each group were processed to measure triglyceride (TG) content, gene expression analysis, western blot analysis, and histological examination including Oil red O staining. 1,8-cineole ameliorated hepatic steatosis in Pten KO mice, revealed by TG content and Oil red O staining. Moreover, 1,8-cineole downregulated collagen 1a1 expression and improved liver fibrosis. Thus, 1,8-cineole has potential as a candidate to treat NASH by inactivating the Akt/PI3-kinase pathway.
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. soichiro@md.tsukuba.ac.jp.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Murata
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. k-ogawa@md.tsukuba.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. t-matsuz@md.tsukuba.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuzaka
authors.affiliation: Department of Biomedical Sciences, Division of Medical Life Sciences, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan. mchiba32@cc.hirosaki-u.ac.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Chiba
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. kenken.nakayama@gmail.com.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. pinpon1225@yahoo.co.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. yuuhaku@gmail.com.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurokawa
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. sanuuuh19@gmail.com.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sano
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. tomohito316@hotmail.com.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Tanoi
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. nokochi3@md.tsukuba.ac.jp.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ohkohchi
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003511:Cyclohexanols / Q000008:administration & dosage* / Q000494:pharmacology; D000077591:Eucalyptol; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D039821:Monoterpenes / Q000008:administration & dosage* / Q000494:pharmacology; D009928:Organ Specificity; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D003511:Cyclohexanols; D039821:Monoterpenes; D014280:Triglycerides; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D000077591:Eucalyptol
keywords: 1,8-cineole; Akt; LXR alpha; NASH; PTEN