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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

(a) Macroscopic and microscopic views of liver of 20-week-old Pten KO mice without any treatment (upper; control) and 1,8-cineole treatment for eight weeks (lower; 1,8-cineole). The liver in the control group (first line upper) was enlarged, where as the liver in the 1,8-cineole group was smaller than that in the control group. HE stained livers of the control group (100× second line upper) and the 1,8-cineole group (100× second line lower) indicate vacuoles in hepatocytes were decreased in the 1,8-cineole group. Lipid accumulation was confirmed by Oil red O staining (100× control; third upper, 1,8-cineole group; third lower). Sirius red staining of the liver (400× control; fourth upper, 1,8-cineole; fourth lower). In the 1,8-cineole group, fibrotic area is narrower than in the control group; (b) Oil red O positive area (%) is compared between the two groups. *, p < 0.05 vs. control group. Control = 4, 1,8-cineole = 5; (c) Hepatic triglyceride content. Control = 5, 1,8-cineole = 6; (d) Hepatic cholesterol content. n = 3 in each group; content was significantly lower in the 1,8-cineole group compared to the control group. * p < 0.05 vs. control.
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ijms-16-12051-f001: (a) Macroscopic and microscopic views of liver of 20-week-old Pten KO mice without any treatment (upper; control) and 1,8-cineole treatment for eight weeks (lower; 1,8-cineole). The liver in the control group (first line upper) was enlarged, where as the liver in the 1,8-cineole group was smaller than that in the control group. HE stained livers of the control group (100× second line upper) and the 1,8-cineole group (100× second line lower) indicate vacuoles in hepatocytes were decreased in the 1,8-cineole group. Lipid accumulation was confirmed by Oil red O staining (100× control; third upper, 1,8-cineole group; third lower). Sirius red staining of the liver (400× control; fourth upper, 1,8-cineole; fourth lower). In the 1,8-cineole group, fibrotic area is narrower than in the control group; (b) Oil red O positive area (%) is compared between the two groups. *, p < 0.05 vs. control group. Control = 4, 1,8-cineole = 5; (c) Hepatic triglyceride content. Control = 5, 1,8-cineole = 6; (d) Hepatic cholesterol content. n = 3 in each group; content was significantly lower in the 1,8-cineole group compared to the control group. * p < 0.05 vs. control.

Mentions: Eight-week continuous intraperitoneal injection of 1,8-cineole ameliorated lipid accumulation of livers compared to the control group. The body weight, liver weight, liver/body weight %, and serum parameters are listed on Table 1. No significant weight loss was observed between the two groups. Liver weight was significantly lower in the 1,8-cineole group. Serum cholesterol of the 1,8-cineole group was significantly decreased compared to the control group. Serum insulin was significantly increased in the 1,8-cineole group. Figure 1a shows gross appearance of liver, HE staining, Oil red O staining, and Sirius red staining. In the 1,8-cineole group, lipid droplet and fibrotic area were decreased compared to the control group. Figure 1b shows the Oil red O positive area and that of the 1,8-cineole group was significantly lower than the control group. Figure 1c shows triglyceride content and Figure 1d shows cholesterol content of the liver. Both triglyceride and cholesterol contents were significantly decreased in the 1,8-cineole group compared to the control group.


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)

(a) Macroscopic and microscopic views of liver of 20-week-old Pten KO mice without any treatment (upper; control) and 1,8-cineole treatment for eight weeks (lower; 1,8-cineole). The liver in the control group (first line upper) was enlarged, where as the liver in the 1,8-cineole group was smaller than that in the control group. HE stained livers of the control group (100× second line upper) and the 1,8-cineole group (100× second line lower) indicate vacuoles in hepatocytes were decreased in the 1,8-cineole group. Lipid accumulation was confirmed by Oil red O staining (100× control; third upper, 1,8-cineole group; third lower). Sirius red staining of the liver (400× control; fourth upper, 1,8-cineole; fourth lower). In the 1,8-cineole group, fibrotic area is narrower than in the control group; (b) Oil red O positive area (%) is compared between the two groups. *, p < 0.05 vs. control group. Control = 4, 1,8-cineole = 5; (c) Hepatic triglyceride content. Control = 5, 1,8-cineole = 6; (d) Hepatic cholesterol content. n = 3 in each group; content was significantly lower in the 1,8-cineole group compared to the control group. * p < 0.05 vs. control.
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Related In: Results  -  Collection

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ijms-16-12051-f001: (a) Macroscopic and microscopic views of liver of 20-week-old Pten KO mice without any treatment (upper; control) and 1,8-cineole treatment for eight weeks (lower; 1,8-cineole). The liver in the control group (first line upper) was enlarged, where as the liver in the 1,8-cineole group was smaller than that in the control group. HE stained livers of the control group (100× second line upper) and the 1,8-cineole group (100× second line lower) indicate vacuoles in hepatocytes were decreased in the 1,8-cineole group. Lipid accumulation was confirmed by Oil red O staining (100× control; third upper, 1,8-cineole group; third lower). Sirius red staining of the liver (400× control; fourth upper, 1,8-cineole; fourth lower). In the 1,8-cineole group, fibrotic area is narrower than in the control group; (b) Oil red O positive area (%) is compared between the two groups. *, p < 0.05 vs. control group. Control = 4, 1,8-cineole = 5; (c) Hepatic triglyceride content. Control = 5, 1,8-cineole = 6; (d) Hepatic cholesterol content. n = 3 in each group; content was significantly lower in the 1,8-cineole group compared to the control group. * p < 0.05 vs. control.
Mentions: Eight-week continuous intraperitoneal injection of 1,8-cineole ameliorated lipid accumulation of livers compared to the control group. The body weight, liver weight, liver/body weight %, and serum parameters are listed on Table 1. No significant weight loss was observed between the two groups. Liver weight was significantly lower in the 1,8-cineole group. Serum cholesterol of the 1,8-cineole group was significantly decreased compared to the control group. Serum insulin was significantly increased in the 1,8-cineole group. Figure 1a shows gross appearance of liver, HE staining, Oil red O staining, and Sirius red staining. In the 1,8-cineole group, lipid droplet and fibrotic area were decreased compared to the control group. Figure 1b shows the Oil red O positive area and that of the 1,8-cineole group was significantly lower than the control group. Figure 1c shows triglyceride content and Figure 1d shows cholesterol content of the liver. Both triglyceride and cholesterol contents were significantly decreased in the 1,8-cineole group compared to the control group.

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