Project Details
Abstract
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
External Project ID:NSC101-2320-B182-017
Status | Finished |
---|---|
Effective start/end date | 01/08/12 → 31/07/13 |
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.