Daily Consumption of Angelica Keiskei Juice Attenuated Hyperlipidaemia and Hepatic Steatosis Caused by Western Diet in C57BL/6J Mice
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2017, Vol 10, Issue 3
Abstract
Background/Objectives: Given that western diet (WD) intake has negative impact on development of non-alcoholic fatty liver disease (NAFLD), the protective effects of Angelica keiskei juice (AK) against hyperlipidemia and hepatic steatosis were investigated in WD-fed C57BL/6J mice. Materials and Methods: Animals were assigned into four groups (n=8/group) to receive normal diet + vehicle, WD + vehicle, WD + low AK (2 g/kg body weight), and WD + high AK (4 g/kg body weight) for 18 weeks. Biochemical analysis was performed for lipid profile in plasma; histological assessment for steatosis, inflammation, and tissue damage in the liver and intestine; and qPCR analysis for intestinal lipoprotein lipase and hepatic endoplasmic reticulum (ER)/oxidative stress markers. Results: AK significantly attenuated WD-induced increases in plasma triglyceride and very low density lipoprotein (P=0.001 for both), and hepatic triglyceride (P<0.001). Particularly, high-dose AK was effective in maintaining intestinal barrier integrity and increasing mRNA expression of hepatic nuclear factor erythroid 2-related factor 2 (P=0.003). It also tended to modify mRNA expressions of intestinal lipoprotein lipase (P=0.004), and hepatic carnitine palmitoyl transferase 1a (P=0.038), endoplasmic reticulum nuclei-1 (P=0.014), and NAD(P)H: quinone oxidoreductase 1 (P=0.047). Conclusions: These findings suggest that daily consumption of AK juice may have potentials to prevent WD-induced NAFLD development through mitigating intestinal barrier damage, intestinal lipid absorption, and hepatic ER oxidative stress. Angelica keiskei, commonly known as Ashitaba, is a cold hardy perennial plant in the genus of Angelica. It has been traditionally used as a tonic to restore vitality [1]. Since 1990s, scientific work has begun to explore the chemo protective effects of chalcone, a bioactive component isolated from Angelica keiskei, both in vitro and in vivo (animals) [2]. In the early 2000s, investigations were expanded to the metabolic effects of Angelica keiskei and/or its bioactives (chalcone and coumarins) including lipid metabolism [3], insulin resistance [4], arterial relaxation [5], oxidative stress [6], inflammation [7], and chemical-induced hepatotoxicity [8,9]. The typical Western diet (WD) is generally characterized by an increase in total fat, saturated fat, and sugars, but a decrease in fiber. The bulk of ingested sugar is rapidly metabolized into glucose6- phosphate which is trapped inside cells. This pathway enables rapid conversion of excess glucose to lipid, resulting in elevated blood lipid levels and exacerbation of triglyceride (TG) storage in the liver. Excess hepatic TG accumulation sensitizes the liver to induce oxidative stress, insulin resistance, and inflammation, eventually leading to hepatocellular damage and death [10]. In addition, high amounts of total fat and saturated fat may alter intestinal barrier integrity and result in direct exposure of intestinal endotoxins to the liver through portal vein [11,12]. Subsequently, these endotoxins can stimulate liver-resident macrophages called Kupffer cells, thereby leading to oxidative stress and inflammation related hepatic damage [13,14]. Furthermore, an additive effect of high-fat and high-sucrose diet on the development of hepatic steatosis was confirmed in mice by Ishimato et al. [15]. Although the best strategy to prevent has not been defined yet, experimental evidence has suggested that plant foods and their constituents might be useful for controlling the onset and progression of WD- induced non-alcoholic fatty liver disease (NAFLD) [16,17]. Based on these findings, we hypothesized that daily consumption of Angelica keiskei might have an impact on reducing WD-induced hyperlipidemia and NAFLD development through enhancing lipid metabolism as well as suppressing the oxidative stress. To test this hypothesis, we performed an animal study using a WD-induced NAFLD mice model. Furthermore, to gain a better understanding on the underlying mechanisms, we analysed histological sections of intestine and liver in relation to intestinal barrier integrity and hepatic steatosis and examined gene expressions associated with oxidative stress in mitochondria and microsome fractions of the liver. To the best of our knowledge, this is the first study that assesses the preventive effect of Angelica keiskei against WD-induced NAFLD. Angelica keiskei juice powder (AK) was provided by Daesang Corp. (Seoul, Korea). Briefly, leaves of Angelica keiskei were grounded, squeezed, and freeze-dried to powder for use in this study. Chemical characteristics of AK were analysed using an Ultimate 3000 UPLC system from Thermo Fisher Scienctific™ (San Jose, CA, USA) and an LTQ Orbitrap Velos Pro™ system mass spectrometer (San Jose, CA, USA). Samples were injected into a Waters ACQUITY® UPLC BEH C18 column (2.1x100mm, 1.7μm) at a temperature of 50 °C. The gradient of elution was performed using mobile phase A (0.1% formic acid in DW) and mobile phase B (0.1% formic acid in methanol) at a flow rate of 0.4mL/min. The gradient condition was regulated as follows: 100% of mobile phase A for 0- 1min, a linear decrease of mobile phase A from 100 to 1% from 1- 13min; and re-equilibration with 100% mobile phase A from 13- 14min. The injection volume of all samples was 5μL. Temperature of the auto sampler was kept at 4 °C. Heated electrospray ionization (HESI) source was used in both positive and negative modes and the capillary temperature was set at 320 °C. The spray voltage was 3.8 kV and the S-lens RF level was 61%. Nitrogen was used as both sheath gas and auxiliary gas. Xcalibur software was used for data analysis.
Authors and Affiliations
Bora Kwon, Soo Yeon Park, Yeni Lim, Byung Hwa Jung, Hyun A Oh, Ji Yeon Kim, Oran Kwon
Keywords
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- EP ID EP587328
- DOI 10.26717/BJSTR.2018.10.001933
- Views 160
- Downloads 0
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