Research Article: Ulmus macrocarpa Hance modulates lipid metabolism in hyperlipidemia via activation of AMPK pathway

Date Published: May 23, 2019

Publisher: Public Library of Science

Author(s): Hye-Ju Han, Xinjie Song, Dhananjay Yadav, Mi Sun Hwang, Joo Hee Lee, Chang Hoon Lee, Tae Hee Kim, Jeong Jun Lee, Jungkee Kwon, Vivek K. Bajpai.


Ulmus macrocarpa Hance as an oriental medicinal plant has shown enormous potential for the treatment of several metabolic disorders in Korea. Hyperlipidemia, which is characterized by the excess accumulation of lipid contents in the bloodstream, may lead to several cardiovascular diseases. Therefore, in this study, anti-hyperlipidemic potential of U. macrocarpa water extract (UME) was examined in vitro and in vivo using HepG2 cells and experimental rats, respectively. The hyperlipidemia in experimental rats was induced by the high-cholesterol diet (HCD) followed by oral administration of various concentrations (25, 50 and 100 mg/kg) of UME for 6 weeks. As a result, the UME significantly improved the biochemical parameters such as increased the level of triglyceride, total cholesterol, and low-density lipoprotein cholesterol as well as reduced the high-density lipoprotein cholesterol in the HCD-fed rats. In addition, UME also prevented lipid accumulation through regulating AMPK activity and lipid metabolism proteins (ACC, SREBP1 and HMGCR) in the HCD-fed rats as compared to the controls. Moreover, similar pattern of gene expression levels was confirmed in oleic acid (OA)-treated HepG2 cells. Taken together, our results indicate that UME prevents hyperlipidemia via activating the AMPK pathway and regulates lipid metabolism. Thus, based on the above findings, it is estimated that UME could be a potential therapeutic agent for preventing the hyperlipidemia.

Partial Text

Hyperlipidemia is known as an abnormal state of lipid metabolism, which is characterized by imbalanced levels of lipid content specifically, increased levels of low-density lipoprotein cholesterol (LDL), total blood cholesterol (TC), and triglyceride (TG) and along with decreased levels of high-density lipoprotein cholesterol (HDL) [1,2]. Moreover, hyperlipidemia places patients at high risk for the development of cardiovascular disease (CVD), including myocardial infarction and stroke [3,4].

Hyperlipidemia is a key risk factor for cardiovascular diseases, which are among the leading causes of mortality throughout the globe [14]. Common characterizations of hyperlipidemia include enhanced levels of TC, TG, and LDL and decreased HDL. These are known to be critical factors in heart diseases, including atherosclerosis and coronary heart disease [15–17]. Previous studies have reported on various statin drugs such as fluvastatin and atorvastatin, which are used to induce hypolipidemia or to prevent hyperlipidemia. Atorvastatin acts by inhibiting HMGCR, the rate-limiting enzyme of the cholesterol biosynthetic pathway [18]. Previous studies have shown that omega-3 reduces TG in hyperlipidemic individuals and may extend to normolipidemic populations [19,20]. Thus, we used these drugs and functional foods as positive controls in the in vivo experiments.




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