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1,8-Cineole Ameliorates Steatosis of Pten Liver Specific KO Mice via Akt Inactivation.

Murata S, Ogawa K, Matsuzaka T, Chiba M, Nakayama K, Iwasaki K, Kurokawa T, Sano N, Tanoi T, Ohkohchi N - Int J Mol Sci (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. soichiro@md.tsukuba.ac.jp.

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.

No MeSH data available.


Related in: MedlinePlus

RT-PCR of the liver messenger RNA in the two groups. (a) fatty acid synthase (FASN); (b) fibroblast growth factor 21 (FGF21); (c) collagen 1A1 (COL1A1); (d) Liver X Receptor alpha (LXR alpha); (e) ATP-binding cassette, sub-family A, member 1 (Abca1); and (f) Glucose 6 Phosphatase (G6P). Data shows relative expression normalized to Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). * p < 0.05, ** p < 0.01 vs. control. n = 3.
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ijms-16-12051-f003: RT-PCR of the liver messenger RNA in the two groups. (a) fatty acid synthase (FASN); (b) fibroblast growth factor 21 (FGF21); (c) collagen 1A1 (COL1A1); (d) Liver X Receptor alpha (LXR alpha); (e) ATP-binding cassette, sub-family A, member 1 (Abca1); and (f) Glucose 6 Phosphatase (G6P). Data shows relative expression normalized to Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). * p < 0.05, ** p < 0.01 vs. control. n = 3.

Mentions: By RT-PCR analysis, FASN, FGF21, and COL1A1 expression were decreased significantly in the 1,8-cineole group compared to the control group (Figure 3a–c). LXR alpha and downstream Abca1 were upregulated significantly compared to the control group (Figure 3d,e). As insulin concentration was restored in the 1,8-cineole group, G6P was upregulated compared to the control group (Figure 3f).


1,8-Cineole Ameliorates Steatosis of Pten Liver Specific KO Mice via Akt Inactivation.

Murata S, Ogawa K, Matsuzaka T, Chiba M, Nakayama K, Iwasaki K, Kurokawa T, Sano N, Tanoi T, Ohkohchi N - Int J Mol Sci (2015)

RT-PCR of the liver messenger RNA in the two groups. (a) fatty acid synthase (FASN); (b) fibroblast growth factor 21 (FGF21); (c) collagen 1A1 (COL1A1); (d) Liver X Receptor alpha (LXR alpha); (e) ATP-binding cassette, sub-family A, member 1 (Abca1); and (f) Glucose 6 Phosphatase (G6P). Data shows relative expression normalized to Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). * p < 0.05, ** p < 0.01 vs. control. n = 3.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490428&req=5

ijms-16-12051-f003: RT-PCR of the liver messenger RNA in the two groups. (a) fatty acid synthase (FASN); (b) fibroblast growth factor 21 (FGF21); (c) collagen 1A1 (COL1A1); (d) Liver X Receptor alpha (LXR alpha); (e) ATP-binding cassette, sub-family A, member 1 (Abca1); and (f) Glucose 6 Phosphatase (G6P). Data shows relative expression normalized to Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). * p < 0.05, ** p < 0.01 vs. control. n = 3.
Mentions: By RT-PCR analysis, FASN, FGF21, and COL1A1 expression were decreased significantly in the 1,8-cineole group compared to the control group (Figure 3a–c). LXR alpha and downstream Abca1 were upregulated significantly compared to the control group (Figure 3d,e). As insulin concentration was restored in the 1,8-cineole group, G6P was upregulated compared to the control group (Figure 3f).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. soichiro@md.tsukuba.ac.jp.

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.

No MeSH data available.


Related in: MedlinePlus