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.

The Essential Oils and Eucalyptol From Artemisia vulgaris L. Prevent Acetaminophen-Induced Liver Injury by Activating Nrf2–Keap1 and Enhancing APAP Clearance Through Non-Toxic Metabolic Pathway

“…AV is one of the famous Artemisia species compared to others such as A. absinthium , A. nilagirica , and A. deserti , (Kazemi et al, 2013; Pelkonen et al, 2013; Sati et al, 2013). AV-EOs have a high content of eucalyptol and Cis-β-Terpineol, which shown anti-inflammatory and antioxidant effects against various diseases, including respiratory disease, pancreatitis, colon damage, and non-alcoholic steatohepatitis (Murata et al, 2015; Seol and Kim, 2016). In our present study, treatment with AV-EOs and eucalyptol significantly attenuated APAP overdose (300 mg/kg) and induced the increase of serum aminotransferase and hepatic histopathological lesions ( Figure 3 ) , suggesting that AV-EOs possess the ability to prevent APAP-induced hepatotoxicity.…”

“…Eucalyptol acted as a strong inhibitor of proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β and showed an analgesic effect in an inflammatory model. Even though there is a report about eucalyptol acting against fatty liver in mammals and zebrafish (Cho, 2012; Murata et al, 2015), the effect and mechanism of eucalyptol against drug-induced liver injury remain unclear.…”

CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice

“…The Oil Red staining was performed as previous described to visualize lipids 46 . Liver sections were de-waxed, rehydrated and stained for standard IHC.…”

“…Liver tissues were fixed in 4% formalin overnight, embedded in paraffin, sectioned at 4 μm and stained with hematoxylin and eosin (H&E) for pathology. The Oil Red staining was performed as previous described to visualize lipids 46 . Liver sections were de-waxed, rehydrated and stained for standard IHC.…”

Amomum cardamomum L. ethyl acetate fraction protects against carbon tetrachloride-induced liver injury via an antioxidant mechanism in rats

“…Another reports suggest that essential oils treatment containing α, β-pinene, d-camphor, and 1,8-cineole inhibited liver injury in animal models [ 27 – 29 ]. 1,8-Cineole, the bicyclic monoterpene rich in A. cardamomum has been reported to have protective bioactivity on liver against steatosis, and 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) in vivo [ 30 , 31 ]. Another study revealed relation between antioxidant activity and hepatoprotection [ 32 , 33 ] which suggests potential effect of A. cardamomum on the liver disease related to free radical and other ROS production.…”