• Title/Summary/Keyword: Alcoholic Fatty Liver

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A mixture of blackberry leaf and fruit extracts decreases fat deposition in HepG2 cells, modifying the gut microbiome

  • Wu, Xuangao;Jin, Bo Ram;Yang, Hye Jeong;Kim, Min Jung;Park, Sunmin
    • Journal of Applied Biological Chemistry
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    • v.62 no.3
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    • pp.229-237
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    • 2019
  • More effective treatments are needed for non-alcoholic fatty liver disease (NAFLD). We hypothesized that water extracts of blackberry fruits (BF) and leaves (BL) and their combinations (BFL) reduce fat deposition in HepG2 cells and modulate shor-tchain fatty acids (SCFA) and fecal bacteria in vitro. HepG2 cells were treated with BF, BL, BFL1:2, and BFL1:3 for 1 h, and 0.5 mM palmitate was added to the cells. Moreover, low ($30{\mu}g/mL$) and high doses ($90{\mu}g/mL$) of BL and BF were applied to fecal bacteria in vitro, and SCFA was measured by GC. BL, BF, BFL1:2, and BFL1:3 reduced triglyceride deposition in the cells in a dose-dependent manner, and BFL1:2 and BFL1:3 had a stronger effect than BF. The content of malondialdehyde, an index of oxidative stress, was also reduced in BL, BF, and BFL1:2 with increasing superoxide dismutase and glutathione peroxidase activities. The mRNA expression of acetyl CoA carboxylase, fatty acid synthase, and sterol regulatory element-binding protein-1c was reduced in BL, BF, BFL1:2, and BFL1:3 compared to the control, and BFL1:2 had the strongest effect. By contrast, the carnitine palmitolytransferase-1expression, a regulator of fatty acid oxidation, increased mostly in BFL1:2 and BFL1:3. Tumor necrosis factor-${\alpha}$ and interleukin-$1{\beta}$ expression was reduced in BL compared to that in BF and BFL1:2 in HepG2 cells. Interestingly, BL increased propionate production, and BF increased butyrate and propionate production and increased total SCFA content in fecal incubation. BF increased the contents of Bifidobacteriales and Lactobacillales and decreased those of Clostridiales, whereas BL elevated the contents of Bacteroidales and decreased those of Enterobacteriales. In conclusion, BFL1:2 and BFL1:3 may be potential therapeutic candidates for NAFLD.

Health beneficial effects of brown algae ecklonia stolonifera in liver (갈조류 곰피(Ecklonia stolonifera)의 간 건강기능성)

  • Yu, Seungmin;Kim, Wooki
    • Food Science and Industry
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    • v.51 no.4
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    • pp.334-342
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    • 2018
  • People in Korea, a peninsular, have acquired a variety of marine food resources including seaweeds. Ecklonia stolonifera, a brown algae, is commonly dwelling in Korean coasts and their cultivation methods were developed for a mass-production. Recently, studies have revealed that Ecklonia stolonifera is a promising material for the development of health functional foods. In an effort to carefully review the current understating in the effects and mechanisms of Ecklonia stolonifera on liver functions by deduction from relevant literatures, the effective components were identified as phlorotannins, including dieckol, eckstolonol, eckol, phlorofucofuroeckol A, and phlorosterol. Their aiding action on the hepatic functions is categorized as follows. A) Regulation of oxidative stress by anti-oxidant capacity, B) Protection of hepatocytes from toxins, C) Prevention of alcoholic fatty liver and fibrogenesis, D) Regulation of chronic disease by improvement of inflammatory responses and lipid metabolisms, and E) indirect benefit conferred by a personal total wellness.

Hepatoprotective Effect of Bacillus subtilis-fermented Silkworm (Bombyx mori L.) Extract on Non-alcoholic Fatty Liver in Rats (고초균 발효누에 추출물이 비알코올성 지방간 유발 흰쥐에 미치는 간 기능 개선 효과)

  • Kim, Tae-Hoon;Ahn, Hee-Young;Kim, Young-Wan;Sim, So-Yeon;Cho, Hyun-Dong;Kim, Man-Do;Lee, You-Jung;Cho, Young-Su
    • Journal of Life Science
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    • v.27 no.9
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    • pp.1031-1039
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    • 2017
  • The aim of this study was to investigate the potential effects of extracts from silkworm Bombyx mori L. fermented with Bacillus subtilis KACC 91157 at levels of 5%(v/w) and 10%(v/w) in Sprague-Dawley rats intoxicated with 1%(w/w) orotic acid (OA) for 10 days. The rats were divided into a normal group (N), a control group (C: OA), and treatment groups (SP10: OA + 10% extracts from B. mori L.; BSP5: OA + 5% extracts from B. mori L. fermented with B. subtilis KACC 91157; BSP10: OA + 10% extracts from B. mori L. fermented with B. subtilis KACC 91157). Serum activities of aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) increased following OA feeding, but the rise was slightly reduced by administration of BSP10. The total lipid, free fatty acid, phospholipid, total cholesterol, and triglyceride contents in serum were significantly lower in the OA treatment groups than in the N group. However, the contents slightly increased following the administration of BSP10. Glutathione concentrations in liver and serum were reduced in the OA-induced fatty liver, but they increased following the administration of BSP10. Hepatocytes in the OA-induced fatty liver contained numerous large droplets. However, SP10, BSP5, and BSP10 feeding prevented OA-induced lipid droplet accumulation in hepatocytes. Accordingly, extracts from silkworm powder fermented with B. subtilis could be an ideal material as a dietary supplement in healthy functional foods to improve the effects of fatty liver.

Effects of Ethanol Extract of Benincasa Seeds on the Experimental Cellular Model of Nonalcoholic Fatty Liver Disease (동과자 에탄올 추출물이 비알코올성 지방간 세포 모델에 미치는 효과)

  • Choi, Jun-Young;Kim, So-Yeon;Kwun, Min-Jung;Kim, Kyun-Ha;Joo, Myung-Soo;Han, Chang-Woo
    • The Journal of Internal Korean Medicine
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    • v.33 no.4
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    • pp.438-447
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    • 2012
  • Objectives : In this study, we investigated the effect and the underlying mechanism of ethanol extract of Benincasa seeds on a cellular model of non-alcoholic fatty liver disease (NAFLD) established by treating HepG2 cells with palmitate. Methods : We evaluated ethanol extract of Benincasa seeds (EEBS) for its hepatic lipid-lowering potential in fatty acid overloaded HepG2 cells. After incubation in palmitate containing media with or without EEBS, intracellular neutral lipid accumulations were quantified by Nile red staining. We also investigated the effect of EEBS on lipogenesis and ${\beta}$-oxidation. $LXR{\alpha}$-dependent SREBP-1c activation, expression of lipogenic genes, and expression of ${\beta}$-oxidation related genes were determined with or without pretreatment of EEBS. Results : EEBS significantly attenuated palmitate-induced intracellular neutral lipid accumulation in HepG2 cells. EEBS suppressed fatty acid synthesis by inhibiting $LXR{\alpha}$-dependent SREBP-1c activation. EEBS also repressed SREBP-1c mediated induction of lipogenic genes, including ACC, FAS, and SCD-1. However, EEBS had no effect on ${\beta}$-oxidation related CPT-1 and $PPAR{\alpha}$ gene expression. Conclusions : Our results suggest that EEBS has an efficacy to decrease hepatic lipid accumulation, and this effect was mediated by inhibiting the $LXR{\alpha}$-SREBP-1c pathway that leads to expression of lipogenic genes and hepatic steatosis. Therefore, the Benincasa seeds may have a potential clinical application for treatment of this chronic liver disease.

Endogenous catalase delays high-fat diet-induced liver injury in mice

  • Piao, Lingjuan;Choi, Jiyeon;Kwon, Guideock;Ha, Hunjoo
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.3
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    • pp.317-325
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    • 2017
  • Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in parallel with worldwide epidemic of obesity. Reactive oxygen species (ROS) contributes to the development and progression of NAFLD. Peroxisomes play an important role in fatty acid oxidation and ROS homeostasis, and catalase is an antioxidant exclusively expressed in peroxisome. The present study examined the role of endogenous catalase in early stage of NAFLD. 8-week-old male catalase knock-out (CKO) and age-matched C57BL/6J wild type (WT) mice were fed either a normal diet (ND: 18% of total calories from fat) or a high fat diet (HFD: 60% of total calories from fat) for 2 weeks. CKO mice gained body weight faster than WT mice at early period of HFD feeding. Plasma triglyceride and ALT, fasting plasma insulin, as well as liver lipid accumulation, inflammation (F4/80 staining), and oxidative stress (8-oxo-dG staining and nitrotyrosine level) were significantly increased in CKO but not in WT mice at 2 weeks of HFD feeding. While phosphorylation of Akt (Ser473) and $PGC1{\alpha}$ mRNA expression were decreased in both CKO and WT mice at HFD feeding, $GSK3{\beta}$ phosphorylation and Cox4-il mRNA expression in the liver were decreased only in CKO-HF mice. Taken together, the present data demonstrated that endogenous catalase exerted beneficial effects in protecting liver injury including lipid accumulation and inflammation through maintaining liver redox balance from the early stage of HFD-induced metabolic stress.

Fermented Protaetia brevitarsis Larvae Ameliorates Chronic Ethanol-Induced Hepatotoxicity in Mice via AMPK and TLR-4/TGF-β1 Pathways

  • Hyo Lim Lee;Jong Min Kim;Min Ji Go;Seung Gyum Joo;Tae Yoon Kim;Han Su Lee;Ju Hui Kim;Jin-Sung Son;Ho Jin Heo
    • Journal of Microbiology and Biotechnology
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    • v.34 no.3
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    • pp.606-621
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    • 2024
  • This study evaluated the hepatoprotective effect of fermented Protaetia brevitarsis larvae (FPB) in ethanol-induced liver injury mice. As a result of amino acids in FPB, 18 types of amino acids including essential amino acids were identified. In the results of in vitro tests, FPB increased alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. In addition, FPB treatment increased cell viability on ethanol- and H2O2-induced HepG2 cells. FPB ameliorated serum biomarkers related to hepatoxicity including glutamic oxaloacetic transaminase, glutamine pyruvic transaminase, total bilirubin, and lactate dehydrogenase and lipid metabolism including triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Also, FPB controlled ethanol metabolism enzymes by regulating the protein expression levels of ADH, ALDH, and cytochrome P450 2E1 in liver tissue. FPB protected hepatic oxidative stress by improving malondialdehyde content, reduced glutathione, and superoxide dismutase levels. In addition, FPB reversed mitochondrial dysfunction by regulating reactive oxygen species production, mitochondrial membrane potential, and ATP levels. FPB protected ethanol-induced apoptosis, fatty liver, and hepatic inflammation through p-AMP-activated protein kinase and TLR-4/NF-κB signaling pathways. Furthermore, FPB prevented hepatic fibrosis by decreasing TGF-β1/Smad pathway. In summary, these results suggest that FPB might be a potential prophylactic agent for the treatment of alcoholic liver disease via preventing liver injury such as fatty liver, hepatic inflammation due to chronic ethanol-induced oxidative stress.

The Effects of Ecklonia stolonifera Extracts on Improvement of Hepatic Function: a Double-Blind, Randomized, Placebo-Controlled Clinical Study (곰피추출물의 간기능 개선 효과 평가를 위한 12주, 무작위배정, 이중맹검, 위약-대조 인체적용시험)

  • Kim, Junghee;Kim, Eun Jin;Kang, Dahye;Kim, Hyung-Bin;Jang, Jae Young;Om, Ae-Son;Kim, Jongwook
    • Journal of Food Hygiene and Safety
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    • v.37 no.3
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    • pp.198-205
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    • 2022
  • Hepatic diseases are divided into two types: alcoholic and non-alcoholic. Non-alcoholic liver injury finally induces fatty liver and damages liver function. Many studies have demonstrated that Ecklonia stolonifera has antioxidative, anti-inflammatory, and hepatoprotective activities. We conducted a 12-week double-blind, placebo-controlled, randomized trial to examine the efficacy of E. stolonifera extracts (ESE) on biochemical markers of hepatic function. Sixty-five subjects with mild or moderate liver injuries were randomly allocated to receive either 420 mg/d of ESE or a placebo for 12 weeks. Fifty-five participants completed the trial. No significant adverse events were observed among the subjects during the study. The primary end points were changes in plasma levels of aspartate transaminase (AST), alanine transaminase (ALT), and γ-glutamyltransferase (γ-GT). The secondary end points were changes in lipid profile levels, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Compared with the baseline, AST and ALT levels decreased significantly in the ESE group compared to those in the placebo group (P<0.001). In addition, γ-GT levels in the ESE group were significantly lower than those in the placebo group (P=0.016). There were no differences in the TC, TG, HDL, and LDL levels between groups. In conclusion, ESE consumption for 12 weeks improved liver parameters in subjects with liver injury. Regular consumption of ESE could maintain liver health in individuals at risk of hepatic damage.

A Study on the Effects and Mechanisms of the Combination Extract of Ephedrae Herba and Coicis Semen on Lipid Accumulation and Glucose Absorption in Non-Alcoholic Fatty Liver Disease (마황과 의이인 혼합추출물이 비알콜성 지방간 모델에서 지질 축적 및 포도당 흡수에 미치는 효과 및 기전 연구)

  • Ga-Ram Yu;Hye-Lin Jin;Dong-Woo Lim;Won-Hwan Park
    • Journal of Korean Medicine for Obesity Research
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    • v.24 no.1
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    • pp.1-12
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    • 2024
  • Objectives: Ephedrae herba (EH) and Coicis semen (CS) has been frequently prescribed for the treatment of obesity. However, effects of combinational extracts of these two herbs on non-alcoholic fatty liver disease are unknown. The aim of the present study was to investigate the effects of EH and CS on lipid accumulation and glucose absorption in free fatty acids (FFAs) or palmitic acid (PA)-treated HepG2 cells. Methods: Five samples of EH and CS were extracted by combination ratios (S1=0:100, S2=25:75, S3=50:50, S4=75:25, S5=100:0). Oil Red O staining was used to measure lipid accumulation in FFAs-induced steatosis cells. Intracellular triglycerides and total cholesterol levels were measured in FFAs-induced steatotic HepG2 cells. In PA-treated cells, intracellular 2-NBDG was detected using a fluorescence microplate reader and flow cytometry. Phosphorylation of key metabolism-related factors of AMP-activated protein kinase and acetyl-CoA carboxylase, expression of key lipid synthesis-related factors carnitine palmitoyltransferase 1 alpha (CPT1α), sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer binding protein alpha (C/EBPα) were confirmed by western blot. Results: Treatment of EH-CS combination in the FFAs-induced steatotic HepG2 cells significantly reduced lipid accumulation. As the relative ratio of Ephedrae herba increased, the lipid-lowering effects of the combination were increased. However, S1 and S5 of Ephedrae herba and Coicis semen did not significantly reduce triglycerides and total cholesterol induced by FFAs. However, the combination of Ephedrae herba and Coicis semen restored glucose absorption in PA-induced HepG2 cells. Major makers of SREBP1, PPARγ, C/EBPα, and CPT1α expression tended to decrease with EH ratio. Conclusions: The EH-CS combination has advantages over sole EH and CS extracts in improving lipid and glucose metabolism in liver steatosis models.

Anti-Lipogenic Effect of Functional Cereal Samples on High Sucrose Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice (고당식이로 유도된 비알코올성 지방간 마우스에서 기능성 잡곡의 지질 대사 개선 효과)

  • Lee, Ko-Eun;Song, Jia-Le;Jeong, Byung-Jin;Jeong, Jong-Sung;Huh, Tae-Gon;Park, Kun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.6
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    • pp.789-796
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    • 2016
  • The anti-lipogenic effect of cereal samples on high sucrose diet (HSD)-induced non-alcoholic fatty liver disease (NAFLD) in mice was studied. We divided C57BL/6 mice into various groups based on 8 weeks of treatment with three types of cereal samples (HSD+WR, HSD diet containing 40% white rice; HSD+MCG, HSD diet containing 40% mixed cereal grain; HSD+AO-MCG, HSD diet containing 40% mixed antiobesity-cereal grain). After the experimental period, body weight changes, liver weights, serum lipid profiles, and hepatic fatty acid metabolism-related gene expression levels were determined. We found that HSD+WR, HSD+MCG, and HSD+AO-MCG treatments reduced body weight and liver weight, especially HSD+MCG and HSD+AO-MCG effectively reduced levels of serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol. However, high density lipoprotein cholesterol levels increased compared to the control group. Furthermore, expression of hepatic lipogenic genes such as sterol regulatory element-binding protein-1c, acetyl-coenzyme A carboxylase, fatty acid synthase, stearoyl-coenzyme A desaturase-1, cluster of differentiation, and $PPAR-{\gamma}$ (peroxisome proliferator activated receptor ${\gamma}$) decreased, whereas expression of ${\beta}-oxidation$ genes such as $PPAR-{\alpha}$ and carnitine palmitoyl transferase-1 increased following HSD+MCG and HSD+AO-MCG treatment compared with levels in HSD+WR and control groups. These results suggest that the functional cereal samples, especially HSD+AO-MCG treatment, improved hepatic steatosis triggered by an HSD-induced imbalance in hepatic lipid metabolism.