• The Korea Journal of Herbology
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• v.27 no.4
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• pp.53-58
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• 2012

Objective : Obesity is often defined as a condition associated with accumulations of excessive body fats which resulting from disorder of energy balance in term of energy intake and energy expenditure. Methods : The effects of natural mixture (T) for inhibition of lipid metabolism on the liver, epididymal fat pads and pancreatic zymogen granules of high fat diet (HFD) supplied rats were observed by histopathology and histomorphometry. Results : As results of HFD supply, severe steatohepatitis such as increases of mean diameters of hepatocytes and the percentages regions of fatty changes was detected. In addition, hypertrophy of adipocytes (increase of mean diameters of epididymal fat pads) was also detected with dramatic decreases of pancreatic zymogen granules at histopathological and histomorphometrical observations. However, theses steatohepatitis and hypertrophy of adipocytes induced by HFD supply were inhibited by treatment of 5 % and 10 % T (T5, T10), respectively. Well corresponded as the results of adipocyte hypertrophy and steatohepatitis, the decreases of pancreatic zymogen granules were also dose-dependently inhibited by T treatment as compared with HFD control, respectively. Conclusion : In conclusion, based on the results, it is considered that test materials, T5 and T10, will be showed hepatoprotective and anti-obese effects, may be directly and/or indirectly mediated by pancreatic zymogen granules because they dose-dependently inhibited steatohepatitis, hypertrophy of adipocytes and decreases of pancreatic zymogen granules induced by HFD supply, respectively.

• The Journal of Korean Medicine
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• v.32 no.3
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• pp.50-54
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• 2011

Objective: To understand the characteristic of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and study the traditional Korean medicine (TKM)-based strategies or therapeutics for them. Methods: A male patient with NASH was treated with only Oriental therapies, and then the clinical outcome was evaluated by serum biochemical parameters and radiographs. Result: The clinical and biochemical values of the patient fluctuated over three years according to the treatments and cessation of herbal medicines. Conclusion: NASH or NAFLD are now prevalent and these disorders could be targets of TKM, and this case report would provide useful information.

• The Journal of Korean Medicine
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• v.32 no.3
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• pp.44-49
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• 2011

Objective: This study aimed to get information on the current status of therapies to date for non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). Methods: All randomized clinical controlled trial (RCT)-derived papers for NAFLD or NASH were reviewed via PubMed Database. Results: 39 RCTs met the review criteria, of which 15 and 24 papers were for NAFLD and NASH, respectively. 83% of the papers were released since 2006, and 30 studies were conducted for western medicines, antioxidants and lifestyle intervention whereas nine trials were done using herbal medicine or acupuncture which showed positive outcome. Conclusions: NAFLD and NASH are new epidemic disorders which can be a target of traditional Oriental medicine. This study will be helpful for the Oriental medicine-based strategies or therapeutic development for them.

• The Journal of Internal Korean Medicine
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• v.38 no.2
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• pp.125-130
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• 2017

Objective: The purpose of this case report is to describe the efficacy of treatment with Korean medicine of a patient with nonalcoholic steatohepatitis (NASH) and metabolic syndrome. Methods: The patient was treated with Korean medicine (Saenggangunbi-tang) from April 27, 2016 to October 22, 2016. Results: Post-treatment, the patient's AST and ALT levels were significantly decreased. Triglyceride levels were within the normal range during the treatment. Abdominal ultrasonography revealed a significant improvement in hepatic steatosis. Conclusions: The results suggest that Saenggangunbi-tang could be an effective treatment for NASH with metabolic syndrome.

• YAKHAK HOEJI
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• v.56 no.1
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• pp.14-19
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• 2012

Nonalcoholic steatohepatitis(NASH) is serious metabolic disease related to fatty acid. According to "two hit theory", fatty acid-induced oxidative stress is important factor to progress nonalcoholic steatohepatitis from steatosis. In this study, we evaluated stearic acid induced oxidative stress in human hepatocarcinoma SK-Hep-1 cell. Cell viability, reactive oxygen species (ROS) production, glutathione (GSH), malondialdehyde and expression of antioxidant enzymes were determined at various time-points and concentrations of stearic acid. At 0.2 mM, non-toxic concentration, of stearic acid, production of ROS was significantly increased at 24 hours and the level of GSH was significantly decreased. Expression of superoxide dismutase-1 and 2 was slightly increased in 0.2 mM stearic acid at 24 hours. These results represent that the non-toxic concentration of stearic acid resulted in oxidative stress, suggesting that stearic acid may play a critical role in development of steatohepatitis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1785-1788
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• 2006

Nonalcoholic steatohepatitis(NASH) may progress to advanced liver disease. The diagnosis is made on liver biopsy when investigating a patient with raised transaminases and an otherwise negative biochemical and serological work-up. The subject was a obese male patient who had unexplained raised GOT, GPT. He had no alcoholic consumption and drug ingested. On serological examination, HBsAg and Anti-HCV test are negative. The subject was diagnosed as NASH, and was treated with oriental treatment for obesity. After 2months treatment the raised GOT, GPT decreased to normal range.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.459-466
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• 2019

Dipeptidyl peptidase (DPP)-4 inhibitors, or gliptins, are a class of oral hypoglycemic drugs that have been widely used as a second-line treatment for type 2 diabetes. Gliptins, which were introduced for clinical use a decade ago, have been shown to be beneficial against nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) in animals and humans. Cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor type 2 and 5, is currently under investigation against NASH and fibrosis. It was previously discovered that evogliptin (EVO) reduces hepatic steatosis in diet-induced obese animals but the effectiveness of EVO on NASH remains unexplored. Here, we compared the effectiveness of EVO and CVC against NASH and fibrosis in mice fed a high-fat and high-fructose diet (HFHF). Biochemical and histological analyses showed that mice fed a HFHF for 20 weeks developed severe hepatic steatosis and inflammation with mild fibrosis. Administration of EVO (0.2% wt/wt) for the last 8 weeks of HFHF feeding significantly reduced hepatic triglyceride accumulation, inflammation, and fibrosis as well as restored insulin sensitivity, as evidenced by lowered plasma insulin levels and the improvement in insulin tolerance test curves. Treatment of mice with CVC (0.1% wt/wt) inhibited hepatic inflammation and fibrogenesis with similar efficacy to that of EVO, without affecting hepatic steatosis. CVC treatment also reduced plasma insulin concentrations, despite no improvement in insulin tolerance. In conclusion, EVO administration efficiently ameliorated the development of NASH and fibrosis in HFHF-fed mice, corroborating its therapeutic potential.

• Journal of Yeungnam Medical Science
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• v.36 no.2
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• pp.67-77
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• 2019

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.133-139
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• 2018

Nonalcoholic steatohepatitis (NASH) is becoming common chronic liver disease because of the increasing global prevalence of obesity and consequently Nonalcoholic fatty liver disease (NAFLD). However, the mechanism for progression of NAFLD to NASH and then cirrhosis is not completely understood, yet. The triggering of these hepatic diseases is thought from hepatocyte injury caused by over-accumulated lipid toxicity. Injured hepatocytes release damage-associated molecular patterns (DAMPs), which can stimulate the Kupffer cells (KCs), liver-resident macrophages, to release pro-inflammatory cytokines and chemokines, and recruit monocyte-derived macrophages (MDMs). The increased activation of KCs and recruitment of MDMs accelerate the progression of NAFLD to NASH and cirrhosis. Therefore, characterization for activation of hepatic macrophages, both KCs and MDMs, is a baseline to figure out the progression of hepatic diseases. The purpose of this review is to discuss the current understanding of mechanisms of NAFLD and NASH, mainly focusing on characterization and function of hepatic macrophages and suggests the regulators of hepatic macrophages as the therapeutic target in hepatic diseases.

• Journal of Yeungnam Medical Science
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• v.29 no.2
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• pp.73-76
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• 2012

More and more children are becoming obese and overweight due to several factors that include a high energy density in the diet (a high fat intake) and low energy expenditure. Consequently childhood obesity is becoming a significant health problem. Fat tissue releases many cytokines such as resistin, tumor necrosis factor-${\alpha}$, leptin, interleukin-6. These adipocytokines induce obesity-related insulin resistance. Insulin resistance is a key component of obesity-related metabolic problems such as hypertension, type 2 diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, acanthosis nigricans and polycystic ovarian syndrome. This review article focused on insulin resistance and its related metabolic diseases.