Caffeoylquinic Acid-Rich Extract of Aster glehni F. Schmidt Ameliorates Nonalcoholic Fatty Liver through the Regulation of PPARδ and Adiponectin in ApoE KO Mice

Hindawi PPAR Research Volume 2017, Article ID 3912567, 19 pages https://doi.org/10.1155/2017/3912567 Research Article Caffeoylquinic Acid-Rich Extract of Aster glehni F. Schmidt Ameliorates Nonalcoholic Fatty Liver through the Regulation of PPAR𝛿 and Adiponectin in ApoE KO Mice Yong-Jik Lee,1 Yoo-Na Jang,1 Yoon-Mi Han,1,2 Hyun-Min Kim,1,2 Jong-Min Jeong,1,2 Min Jeoung Son,3 Chang Bae Jin,3 Hyoung Ja Kim,3 and Hong Seog Seo1,2 1 Cardiovascular Center, Korea University, Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, Republic of Korea Department of Medical Science, Korea University College of Medicine (BK21 Plus KUMS Graduate Program), Main Building 6F Room 655, 73 Inchon-ro (Anam-dong 5-ga), Seongbuk-gu, Seoul 136-705, Republic of Korea 3 Molecular Recognition Research Center, Materials and Life Science Research Division, Korea Institute of Science and Technology, Hwarangno 14 Gil 5, Seoul 136-791, Republic of Korea 2 Correspondence should be addressed to Hyoung Ja Kim; and Hong Seog Seo; Received 11 April 2017; Revised 4 June 2017; Accepted 10 September 2017; Published 23 October 2017 Academic Editor: Henrike Sell Copyright © 2017 Yong-Jik Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aster glehni is well known for its therapeutic properties. This study was performed to investigate the effects of A. glehni on nonalcoholic fatty liver disease (NAFLD) in atherosclerotic condition, by determining the levels of biomarkers related to lipid metabolism and inflammation in serum, liver, and adipose tissue. Body and abdominal adipose tissue weights and serum triglyceride level decreased in all groups treated with A. glehni. Serum adiponectin concentration and protein levels of peroxisome proliferator-activated receptor 𝛿, 5󸀠 adenosine monophosphate-activated protein kinase, acetyl-CoA carboxylase, superoxide dismutase, and PPAR𝛾 coactivator 1-alpha in liver tissues increased in the groups treated with A. glehni. Conversely, protein levels of ATP citrate lyase, fatty acid synthase, tumor necrosis factor 𝛼, and 3-hydroxy-3-methylglutaryl-CoA reductase and the concentrations of interleukin 6 and reactive oxygen species decreased upon A. glehni. Triglyceride concentration in the liver was lower in mice treated with A. glehni than in control mice. Lipid accumulation in HepG2 and 3T3-L1 cells decreased upon A. glehni treatment; this effect was suppressed in the presence of the PPAR𝛿 antagonist, GSK0660. Our findings suggest that A. glehni extracts may ameliorate NAFLD through regulation of PPAR𝛿, adiponectin, and the related subgenes. 1. Introduction Nonalcoholic fatty liver disease (NAFLD), characterized by the accumulation of triglyceride in hepatocytes, is one of the most common diseases today. Metabolic disorders such as obesity, diabetes mellitus, and hyperlipidemia are major risk factors for NAFLD and nonalcoholic steatohepatitis (NASH), which is a more severe form of NAFLD [1, 2]. Furthermore, NAFLD can be used as a representative clinical index of hypertension, cardiovascular disease, and diabetic complications [3, 4]. Adiponectin is an adipocytokine consisting of 244 amino acid residues and is specifically and highly expressed in adipose tissues [5]. Its expression is closely related to various metabolic diseases such as obesity, type 2 diabetes, atherosclerosis, and cardiovascular disease [6, 7]. In addition, soybean embryo ameliorates nonalcoholic fatty liver through adiponectin mediated 5󸀠 adenosine monophosphate-activated protein kinase 𝛼 (AMPK 𝛼) pathway [8]. AMPK normalizes lipid homeostasis through several mechanisms. It downregulates cholesterol and fatty acid syntheses by inactivating the enzymes 3-hydroxy-3methylglutaryl-CoA reductase (HMGCR) and fatty acid synthase (FASN), respectively. Further, AMPK upregulates fatty acid oxidation by inhibiting acetyl-CoA carboxylase (ACC) [9–11]. Throughout human history, many plants have been consumed not only as food, but also for preventing or even curing certain diseases. For instance, Aster glehni has been used in 2 cooking and as traditional medicine for hundreds of years in Korea. In the Dongui Bogam, a Korean traditional medical encyclopedia, it is recorded that A. glehni exhibits antipyretic and analgesic activities and reduces phlegm and coughing. In addition, various therapeutic functions of A. glehni extract such as antiobesity, antioxidation, anti-inflammation, and antiwrinkle activities have been recently reported [12–14]. These studies suggest the potential antiadipogenesis and antiobesity effects of A. glehni and its therapeutic potential in treating obesity-related diseases. Hitherto, there are few studies on the effects of A. glehni on metabolic diseases. Because many studies have reported a close correlation between NAFLD and cardiovascular diseases such as hypertension and atherosclerosis, we investigated the effect of A. glehni on nonalcoholic fatty liver in atherosclerotic mice and it was conducted with focusing on PPAR𝛿. The present findings can be beneficial in further understanding the role of phytomedicines in treating atherosclerosis and fatty liver disease. 2. Materials and Methods 2.1. Plant Material. Parboiled and dried A. glehni F. Schmidt (family Compositae) were purchased from Ulleung Island, Gyeongsangbuk-do, Korea, in November 2012 and identified by Professor Chang-Soo Yook (Department of Pharmacognosy, Kyung Hee University, Seoul, Korea). Voucher specimens (971-12A-P) were deposited in the herbarium of the Korea Institute of Science and Technology. 2.2. Extraction Procedure. Chopped leaves and stem of A. glehni (12 kg) were extracted three times with methanol (70 L) at room temperature to give a methanol-soluble extract. The dried extract residue (2.6 kg) was suspended in water and partitioned with ethyl acetate. The ethyl acetate fraction was evaporated under reduced pressure to yield 41.0 g of residue. Organic solvents used in the extraction procedure were purchased from Sigma-Aldrich (St. Louis, MO, USA). 2.3. High-Performance Liquid Chromatography (HPLC) Analysis for Ethyl Acetate Extract of A. glehni. The ethyl acetate extract of A. glehni was analyzed using reverse-phase highperformance liquid chromatography (Waters 1500 Series System), with a 2998 PDA Detector (Waters, Worcester, MA, USA). Separation was performed using a Luna C18 column (5 𝜇m, 250 × 4.6 mm, Phenomenex, Torrance, CA, USA) at 25∘ C with a sample injection volume of 10 𝜇L. The mobile phase was a gradient of methanol and 1% acetic acid. The following gradient was used: 30% methanol (0 min), 40% methanol (0∼10 min), 60% methanol (10∼20 min), 80% methanol (20∼30 min), and 100% methanol (30∼40 min). The flow rate of the mobile phase was 1.0 ml/min. Organic solvents used in HPLC analysis were purchased from SigmaAldrich. 2.4. Cell C (...truncated)