Amides Constituents of Achillea millefolium Repairs Hepatic mTOR/AKT Signalling and Attenuates Lipid Abnormity in Obesity Mice with Fatty Liver

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Background: The accumulation of free fatty acids plays a role in the induction of steatosis and mitochondria dysfunction in hepatocyte. Thus factors that effect lipogenesis and mitochondria dysfunction may be used to modulate fatty liver. Increase in mTOR activity and due to an alteration in fat vesicle in hepatocytes. In obesity and obesity-related liver disease the mTOR/AKT pathway can contribute to mitochondria dysfunction, to lipid abnormity, and to progression of fatty liver disease. Achillea millefolium is one kind of Asteraceae plants. It was distributed in the northern hemisphere. It has been used as a curative from number of ailments, such as bleeding, cold, stomach complaints and reduced blood glucose. Thus, developing protective strategies from herbal medicine to minimize the liver injury in steatotic livers is an urgent need. Material and Methods: The fresh whole plant of A. millefolium was extracted by methanol. The crude extract was suspended in water and partitionated with n-hexane, EtOAc, separately. Each layer was analysed by column chromatography, thin layer chromatography to isolate pure compounds. The compounds were isolated from the A. millefolium. Their structures were determined by spectral analysis and compared with literature data. The main purpose of the current study will evaluate whether the “amides” constituents from A. millefolium reduce the vulnerability of steatotic livers. The second purpose of this study will evaluate whether the benefits of the “amides” constituents from A. millefolium involving in hepatic steatosis could be explained by change in hepatic mTOR/AKT signaling pathways. The third aim of this study will test whether the protection by the “amides” constituents from A. millefolium against fatty livers is associated with reduce HIF-1α activation, oxidative stress, and mitochondria dysfunction. Accordingly, the fourth aim of the present study will address whether the the “amides” constituents from A. millefolium is able to against fatty liver injury and affect the SREBP-1, which mediates the gene response to lipid accumulation in a mouse model of obesity. For this purpose, we chose the high fat diet induced obese mouse, characterized by hyperphagia, decreased energy expenditure, and early onset of obesity. In the first year, we challenged hepatocytes with high concentrations of a mixture of oleate and palmitate (HFFA) as a model of hepatic lipogenesis and impairment of mitochondria function. The “amides” constituents from A. millefolium may prevented HFFA -stimulated change in intracellular triglyceride levels, the generation of ROS, and mitochondria membrane potential (MMP), and reverse impairments in the phosphorylation factors associated with signaling as mTOR and AKT expression. In the second year,, the “amides” constituents from A. millefolium may suppression of steatosis was reflected by a lowering in liver triglyceride content as compared with male C57BL/6 mice which fed high fat diet for 20 weeks obese animals. In addition, the “amides” constituents from A. millefolium. may simultaneously decreased hepatic fatty acid synthesis (SREBP-1c, FAS) and increased β-oxidation (CPT-1, CPT-2) genes expression of obesity mice. Potential significant: Therefore, we will identify and study the “amides”constituents, originated from A. millefolium responsible for lipogenesis and steatosis. Especially investigate the amides constituents involving in the mechanisms by signaling in regulation of fatty acid synthase in vitro and in vivo study. Understanding of the molecular mechanisms of A. millefolium, especially on the role of mTOR/AKT pathways may lead to develop more effective therapeutic strategies in liver diseases in the future.

Project IDs

Project ID:PC10108-0922
External Project ID:NSC101-2320-B182-017
Effective start/end date01/08/1231/07/13


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