• 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.

• BMB Reports
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• v.49 no.3
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• pp.139-148
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• 2016

In the past decade, the incidence of type 2 diabetes (T2D) has rapidly increased, along with the associated cardiovascular complications. Therefore, understanding the pathophysiology underlying T2D, the associated complications and the impact of therapeutics on the T2D development has critical importance for current and future therapeutics. The prevailing feature of T2D is hyperglycemia due to excessive hepatic glucose production, insulin resistance, and insufficient secretion of insulin by the pancreas. These contribute to increased fatty acid influx into the liver and muscle causing accumulation of lipid metabolites. These lipid metabolites cause dyslipidemia and non-alcoholic fatty liver disease, which ultimately contributes to the increased cardiovascular risk in T2D. Therefore, understanding the mechanisms of hepatic insulin resistance and the specific role of liver lipids is critical in selecting and designing the most effective therapeutics for T2D and the associated co-morbidities, including dyslipidemia and cardiovascular disease. Herein, we review the effects and molecular mechanisms of conventional anti-hyperglycemic and lipid-lowering drugs on glucose and lipid metabolism.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.3
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• pp.199-206
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• 2016

Purpose: To analyze the associations among the degrees of nonalcoholic fatty liver disease (NAFLD) by ultrasonography and metabolic syndrome, degrees of obesity in children, and degrees of parental obesity. Methods: A total of 198 children with obesity who visited a pediatric obesity clinic were prospectively enrolled in this study. The severity of NAFLD based on ultrasonography was classified into no, mild, moderate, or severe NAFLD group. The degree of obesity based on the percentage over standard weight for height per sex was classified into mild, moderate, or severe. Results: Of 132 patients evaluated for the degree of NAFLD and metabolic syndrome, the p-value of correlation between the two factors was 0.009. Therefore, metabolic syndrome might significantly affect the degree of NAFLD. Of 158 patients evaluated for the degree of NAFLD and the degree of obesity, the p-value of correlation between the two factors was 0.122. Of 154 patients evaluated for the degree of obesity and father's obesity, the p-value was 0.076. Of 159 patients evaluated for the degree of obesity and mother's obesity, the p-value was 0.000, indicating that mother's obesity could significantly affect the degree of obesity in children. Of 142 patients evaluated for the degree of obesity and metabolic syndrome, the p-value was 0.288. Conclusion: Metabolic syndrome might significantly affect the degree of nonalcoholic fatty liver in children. In addition, mother's obesity might be a significant factor that affects the degree of obesity in children.

• Health Policy and Management
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• v.31 no.4
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• pp.472-478
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• 2021

Background: Early identification of patients who are highly likely to develop severe illness among confirmed cases of coronavirus disease 19 (COVID-19) can be expected to lead to effective treatment. This study therefore aimed to determine whether the presence of nonalcoholic fatty liver disease (NAFLD) has an impact on the exacerbation of COVID-19 symptoms. Methods: The study used the Korean National Health Insurance claim data for treatment of COVID-19 patients in 2020. NAFLD includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The outcome variables used were hospitalization and the use of medical devices. Hospitalization was defined by a length of stay exceeding one day and the use of medical devices was defined as one or more uses of a ventilator or extracorporeal membrane oxygenation. Multivariable logistic regression analysis was performed to determine if there was a difference in the hospitalization and use of medical devices of COVID-19 patients depending on the presence of NAFLD. Results: The odds ratio of hospitalization was 1.059, indicating slightly higher odds of hospitalization for patients with NAFL or NASH compared to those without the conditions, but it was not statistically significant (0.969-1.156). On the other hand, the odds ratio of use of medical devices was high at 1.667 and was statistically significant (1.111-2.501). Conclusion: The study results found NAFLD to be a risk factor that can exacerbate symptoms in COVID-19 patients. Accordingly, it is necessary to identify NAFLD patients through preemptive screening and provide them with appropriate treatments.

• The Journal of Internal Korean Medicine
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• v.41 no.3
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• pp.542-551
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• 2020

Objectives: The purpose of this study was to retrospectively assess the effectiveness of Chunggan plus extract (CGX) in improving liver function in a Korean medical clinic. Methods: We collected the data of inpatients who received CGX to improve abnormal liver function test (LFT) results from March 2016 to February 2020. We analyzed the changes in LFT and adverse events based on subjective symptom changes and creatinine results. Results: The data of eight patients, three male and five female, were selected by inclusion criteria (patients who did LFT before and after the prescription of CGX and who prescribed CGX more than 6 days) and exclusion criteria (patients who administered other herbal medicine for improving liver function except CGX and who are diagnosed with terminal stage of hepatobiliary cancer). As a cause of abnormal LFT, one case was diagnosed with alcoholic liver disease, two cases with non-alcoholic fatty hepatitis, and one case with cholecystitis. Three of the other four were suspected to have drug-induced hepatitis, and one case was determined to have an unknown cause. Most patients showed a decrease in LFT results (Aspartate transaminase 87.5%, Alanine transaminase 87.5%, and Alkaline Phosphatase 100%) without any critical adverse events. Conclusions: CGX may be an efficient and convenient herbal medicine for improving liver function regardless of the chief impression. Further study should be conducted to evaluate the effectiveness of CGX.

• 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.

• 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.

• 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.

• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.391-398
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• 2022

Polyploidization is a process by which cells are induced to possess more than two sets of chromosomes. Although polyploidization is not frequent in mammals, it is closely associated with development and differentiation of specific tissues and organs. The liver is one of the mammalian organs that displays ploidy dynamics in physiological homeostasis during its development. The ratio of polyploid hepatocytes increases significantly in response to hepatic injury from aging, viral infection, iron overload, surgical resection, or metabolic overload, such as that from non-alcoholic fatty liver diseases (NAFLDs). One of the unique features of NAFLD is the marked heterogeneity of hepatocyte nuclear size, which is strongly associated with an adverse liver-related outcome, such as hepatocellular carcinoma, liver transplantation, and liver-related death. Thus, hepatic polyploidization has been suggested as a potential driver in the progression of NAFLDs that are involved in the control of the multiple pathogenicity of the diseases. However, the importance of polyploidy in diverse pathophysiological contexts remains elusive. Recently, several studies reported successful improvement of symptoms of NAFLDs by reducing pathological polyploidy or by controlling cell cycle progression in animal models, suggesting that better understanding the mechanisms of pathological hepatic polyploidy may provide insights into the treatment of hepatic disorders.

• 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.