• The Journal of Internal Korean Medicine
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• v.33 no.4
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• pp.533-542
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• 2012

Objectives : We try to compared the efficacy of six herbal medicines, Rhizoma Alismatis (RA), Fructus Crataegi (FC), Fructus Lycii (FL), Radix Curcumae (RC), Radix Salviae Miltiorrhizae (RSM), and Herba Artemisiae Scopariae (HAS), constituting KHchunggan-tang which was previously proven to be hepatoprotective on non-alcoholic fatty liver disease with combined properties of cellular steatosis, ROS production, and cytoprotection. Methods : HepG2 cells were pretreated with aqueous extracts of the six herb medicines at concentrations of 1, 10, 50 and 100 ${\mu}g/ml$ each, and treated with 0.5 mM palmitate consecutively. After 21 hrs, cell viability was assessed using MTT assay, and the percentage of cells with sub-G1 DNA content was measured using fluorescence-activated cell sorting after propidium iodide staining. Results : The first three extracts, RA, FC, and FL restored cell viability reduced by palmitate in MTT assay, and RA, FC, FL and RC inhibited palmitate-induced apoptosis in sub-G1 analysis. FL showed relatively weak potential only at tested maximal dose, and RA showed the greatest higher efficacy on this experimental cellular model of nonalcoholic fatty liver disease. Conclusions : According to this comparative experiment, Rhizoma Alismatis seems to have the most powerful potential among the six herbs constituting KHchunggan-tang, and consecutive further study seems to be required for more standardized and effective clinical application of KHchunggan-tang for treatment of non-alcoholic fatty liver disease.

• 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 Korean Journal of Food And Nutrition
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• v.35 no.5
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• pp.332-342
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• 2022

Nonalcoholic fatty liver disease (NAFLD) is recognized one of the leading metabolic diseases globally, and the younger age population with the disease is rapidly growing, especially in developed countries. Since there has been no approved medicine, losing weight is known to be the only best remedy to control or reverse the disease. Recently, the field of microbiome has attracted much attention to offer more practical choices for patients. Here, we provide experimental evidence that Streptococcus thermophilus LM1012 (LM1012), a safe probiotic strain, is effective for improving NAFLD indexes. In the methionine-choline deficient (MCD) diet induced C57BL/6 mouse model, administration of LM1012 promoted marked reductions of aspartate transaminase (23.8%), total bilirubin (27.8%), hydroxycholesterol (64.2%), triglyceride (29.7%) and IL-1β (68.3%) compared to the MCD diet alone group. Also, the histopathological data imply that LM1012 inhibited fat accumulation and inflammation in the liver, which are the key biomarkers for progression of the disease. Together, these findings suggest that human consumption of LM1012 as a healthy nutritional supplement, may be helpful in reducing the risk of liver damages in NAFLD patients.

• BMB Reports
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• v.54 no.6
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• pp.323-328
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• 2021

Periodontal diseases have been reported to have a multidirectional association with metabolic disorders. We sought to investigate the correlation between periodontitis and diabetes or fatty liver disease using HFD-fed obese mice inoculated with P. gingivalis. Body weight, alveolar bone loss, serological biochemistry, and glucose level were determined to evaluate the pathophysiology of periodontitis and diabetes. For the evaluation of fatty liver disease, hepatic nonalcoholic steatohepatitis (NASH) was assessed by scoring steatosis, inflammation, hepatocyte ballooning and the crucial signaling pathways involved in liver metabolism were analyzed. The C-reactive protein (CRP) level and NASH score in P. gingivalis-infected obese mice were significantly elevated. Particularly, the extensive lobular inflammation was observed in the liver of obese mice infected with P. gingivalis. Moreover, the expression of metabolic regulatory factors, including peroxisome proliferator-activated receptor γ (Pparγ) and the fatty acid transporter Cd36, was up-regulated in the liver of P. gingivalis-infected obese mice. However, inoculation of P. gingivalis had no significant influence on glucose homeostasis, insulin resistance, and hepatic mTOR/AMPK signaling. In conclusion, our results indicate that P. gingivalis can induce the progression of fatty liver disease in HFD-fed mice through the upregulation of CD36-PPARγ axis.

• The Journal of the Korea Contents Association
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• v.9 no.6
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• pp.237-246
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• 2009

This study was carried out to investigate of the associations of Alcoholic & Nonalcoholic fatty liver disease(AFLD & NAFLD) with metabolic syndrome(MS) defined by IDF criteria. We conducted a cross-sectional study of 799 adult males with alcohol consumption underwent laboratory investigation(control 297, alcoholic 206, nonalcoholic 296). The ultrasound scan of the liver was performed to determine the presence and the severity of FLD. We analyzed the association between the severity of AFLD & NAFLD and MS by logistic regression analysis. The distribution of metabolic syndrome was 7.4%, 48.8%, 34.9% in control, AFLD & NAFLD. The association of blood pressure, glucose, triglycerides, obesity were risk factor in AFLD & NAFLD. According to the severity of FLD, AFLD was significantly increased with MS, Obesity, low HDL-cholesterol. MS, High triglycerides was increased significantly in NAFLD(p<0.05). The prevalence of AFLD & NAFLD was increased with increasing the number of features of metabolic syndrome. This study shows that AFLD & NAFLD was closely associated with MS and its components. The patients of AFLD & NAFLD should managed and monitored to prevent metabolic abnormalities.

• Toxicological Research
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• v.35 no.4
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• pp.403-410
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• 2019

Curcumin, a hydrophobic polyphenol isolated from the Curcuma longa L. plant, has many pharmacological properties, including antioxidant, anti-inflammatory, and chemo-preventive activities. Curcumin has been shown to have potential in preventing nonalcoholic fatty liver disease (NAFLD). However, the low bioavailability of curcumin has proven to be a major limiting factor in its clinical adoption. Theracurmin, a highly bioavailable curcumin that utilizes micronized technology showed improved biological absorbability in vivo. The aim of this study was to investigate the role of theracurmin in modulating hepatic lipid metabolism in vivo. A fatty liver mouse model was produced by feeding mice a high fat diet (HFD; 60% fat) for 12 weeks. We found that treatment for 12 weeks with theracurmin significantly lowered plasma triacylglycerol (TG) levels and reduced HFD-induced liver fat accumulation. Theracurmin treatment lowered hepatic TG and total cholesterol (T-CHO) levels in HFD-fed mice compared to controls. In addition, theracurmin administration significantly reduced lipid peroxidation and cellular damage caused by reactive oxygen species in HFD-fed mice. Overall, these results suggest that theracurmin has the ability to control lipid metabolism and can potentially serve as an effective therapeutic remedy for the prevention of fatty liver.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.316-324
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• 2021

Background: Korea Red Ginseng (KRG) has been used as remedies with hepato-protective effects in liver-related condition. Microbiota related gut-liver axis plays key roles in the pathogenesis of chronic liver disease. We evaluated the effect of KRG on gut-liver axis in patients with nonalcoholic statohepatitis by the modulation of gut-microbiota. Methods: A total of 94 patients (KRG: 45 and placebo: 49) were prospectively randomized to receive KRG (2,000 mg/day, ginsenoside Rg1+Rb1+Rg3 4.5mg/g) or placebo during 30 days. Liver function test, cytokeraton 18, and fatigue score were measured. Gut microbiota was analyzed by MiSeq systems based on 16S rRNA genes. Results: In KRG group, the mean levels (before vs. after) of aspartate aminotransferase (53 ± 19 vs. 45 ± 23 IU/L), alanine aminotransferase (75 ± 40 vs. 64 ± 39 IU/L) and fatigue score (33 ± 13 vs. 26 ± 13) were improved (p < 0.05). In placebo group, only fatigue score (34 ± 13 vs. 31 ± 15) was ameliorated (p < 0.05). The changes of phyla were not statistically significant on both groups. In KRG group, increased abundance of Lactobacillus was related with improved alanine aminotransferase level and increased abundance of Clostridium and Intestinibacter was associated with no improvement after KRG supplementation. In placebo group, increased abundance of Lachnospiraceae could be related with aggravation of liver enzyme (p < 0.05). Conclusion: KRG effectively improved liver enzymes and fatigue score by modulating gut-microbiota in patients with fatty liver disease. Further studies are needed to understand the mechanism of improvement of nonalcoholic steatohepatitis. ClnicalTrials.gov: NCT03945123 (www.ClinicalTrials.gov).

• Clinical and Experimental Pediatrics
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• v.59 no.9
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• pp.362-367
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• 2016

Purpose: This study aimed to investigate the clinical significance of serum alanine aminotransferase (ALT) levels in children with nonalcoholic fatty liver disease (NAFLD) and the effect of lifestyle intervention on NAFLD. Methods: The clinical data of 86 children diagnosed with NAFLD were reviewed retrospectively. Forty-six patients belonged to the elevated ALT group and 40 to the normal ALT group. The clinical parameters of patients with NAFLD were also compared based on the status of ALT levels after lifestyle intervention. Results: Patients with elevated ALT had significantly higher body mass index (BMI) scores than those with normal ALT (P<0.05). Of all the patients with elevated ALT, 89% exhibited moderate or severe degree of fatty change in the liver on ultrasonographic examination, whereas most patients with normal ALT exhibited mild or moderate degree changes. Liver biopsy was performed in 15 children with elevated ALT and all showed mild histological changes. Of all patients with elevated ALT, 49% achieved normal ALT levels after lifestyle intervention. Those with more severe histological changes tended to have continuously increasing ALT levels. There was no correlation between the normalization of posttreatment ALT level and BMI, as well as ultrasonographic findings at diagnosis. Conclusion: ALT elevation in NAFLD is highly associated with higher BMI scores and more severe degree of fatty changes on ultrasonographic examination. Lifestyle intervention can significantly improve ALT in children with NAFLD. The degree of histologic changes appears to be a predictor of the treatment response to NAFLD.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.350-361
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• 2020

Background: Black ginseng (BG) is a type of Korean ginseng prepared by steaming and drying raw ginseng to improve the saponin content. This study examined the effects of BG on nonalcoholic fatty liver disease (NAFLD) in HepG2 cells and diet-induced obese mice. Methods: HepG2 cells were treated with free fatty acids to induce lipid accumulation before supplementation with BG. NAFLD-induced mice were fed different doses (0.5%, 1%, and 2%) of BG for 8 weeks. Results: BG significantly reduced lipid accumulation and expression of lipogenic genes, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, sterol regulatory element-binding protein-1c, and fatty acid synthase in HepG2 cells, and the livers of mice fed a 45% high-fat diet with 10% fructose in the drinking water (HFHF diet). BG supplementation caused a significant reduction in levels of aspartate aminotransferase and alanine aminotransferase, while antioxidant enzymes activities were significantly increased in 45% high-fat diet with 10% fructose in the drinking water diet-fed mice. Expression of proliferator-activated receptor alpha and carnitine palmitoyltransferase I were upregulated at the transcription and translation levels in both HepG2 cells and diet-induced obese mice. Furthermore, BG-induced phosphorylation of AMP-activated protein kinase and acetyl CoA carboxylase in both models, suggesting its role in AMP-activated protein kinase activation and the acetyl CoA carboxylase signaling pathway. Conclusion: Our results indicate that BG may be a potential therapeutic agent for the prevention of NAFLD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.3
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• pp.168-174
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• 2015

Purpose: Recent studies have suggested that decreased serum potassium level may contribute to various metabolic disorders in adult patients including nonalcoholic fatty liver disease (NAFLD). We aimed to study the correlation between serum potassium levels and the histologic severity of NAFLD in children. Methods: Pediatric patients with biopsy-proven NAFLD were included in this study. Demographic, clinical, and histopathological data were obtained. Multivariable logistic regression analysis was used to assess whether potassium levels are associated with the presence of nonalcoholic steatohepatitis (NASH) or fibrosis after adjusting for possible confounders. A p-value <0.05 was considered statistically significant. Results: Among 125 biopsies, 49.6% (62) had evidence of NASH while 66.4% (83) had some degree of fibrosis (stage 1-3). Mean serum potassium was significantly lower in NASH group as compared to non-NASH group ($4.4{\pm}0.42mmoL/L$ vs. $4.8{\pm}0.21$, p<0.001). Higher potassium level had negative correlation with presence of steatosis, ballooning, lobular inflammation, fibrosis and NAFLD activity score (p<0.05). On multivariable analysis and after adjusting for the metabolic syndrome and insulin resistance, higher potassium level was significantly associated with lower likelihood of having a histological diagnosis of NASH on biopsy (odds ratio [OR], 0.12; 95% confidence interval [95% CI], 0.05-0.28; p<0.001). Similarly, the likelihood of having fibrosis decreases by 76% for every 0.5 mmoL/L increase in potassium (OR, 0.24; 95% CI, 0.11-0.54; p<0.001). Conclusion: Our study shows an inverse relationship between serum potassium levels and the presence of aggressive disease (NASH and fibrosis) in children with NAFLD.