• 대한본초학회지
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• 제33권5호
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• pp.1-8
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• 2018

Objectives : The aim of this study is to investigate the preventive effect of Puerariae Flos ethanol extract (PE) on methionin and choline deficient (MCD)-diet-induced Nonalcoholic fatty liver disease (NAFLD) in C57BL/6J mice. Methods : In the in vivo experiments, C57BL/6J mice were divided into 4 groups; Normal group, Control group, MCD+PE 100 group, and MCD+PE 300 group. After 4 weeks, body weight, liver weight, biochemical parameters for liver function test, histological changes, reverse transcription polymerase chain reaction (RT-PCR), and Western blot were assessed. Results : Mice lost body weight with the MCD-diet and the MCD+PE 100 group and MCD+PE 300 groups lost less than the control group, though showed no statistical significance. Liver weights were decreased by the MCD diet, but MCD+PE 300 groups were increased significantly. In the liver function test, all the values were decreased with the MCD-diet, MCD+PE 100 group and MCD+PE 300 groups were increased significance. In histological findings of the livers, MCD-diet induced severe fatty accumulation in the livers, but this fatty change was reduced in the MCD+PE 100 group and MCD+PE 300 groups was inhibited respectively. In lipid accumulation factors (such as SREBP-1c, $C/EBP{\alpha}$, PPAR-${\gamma}$), MCD+PE 100 group and MCD+PE 300 groups showed inhibitory effect on liver lipogenesis by reducing associated gene expressions caused by MCD diet. Conclusions : We were able to know that Puerariae Flos ethanol extract (PE) shown hepatoprotective effects via a decrease on the hepatic lipogenesis factors in the experimental NAFLD Models.

• 대한한방내과학회지
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• 제30권2호
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• pp.410-421
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• 2009

Objective : The aim of this study is to investigate the preventive effect of Injinchunggan-tang (YJCGT) & Injinysaryung-san (YJSRS) on MCD-diet-induced NASH in A/J mice. Methods : A/J mice were divided into 4 groups: Normal group (normal diet without any treatment). Control group (MCD diet only), YJCGT group (MCD diet with YJCGT), and YJSRS group (MCD diet with YJSRS). After 5 weeks, body weight, liver weight, biochemical parameters for liver function test, histological changes, and real-time PCR were assessed. Results : Mice lost body weight with the MCD diet and the YJCGT and YJSRS groups lost less than the control group, though showed no statistical significance. Liver weights were decreased by the MCD diet, but not significantly. In the liver function test, all the values were increased with the MCD diet, though some did not show significance. Alp and ALT levels were significantly less increased by YJCGT compared to the normal (p<0.05). All values were decreased or increased compared to the control by treatment though showed no significance possibly due to insufficient sample numbers. In histological findings of the livers. MCD-diet induced severe fatty change and collagen accumulation in the livers, but this fatty change was reduced in the YJCGT and YJYRS groups and fibrogenesis was inhibited significantly with p<0.05 and p<0.01, respectively. In real-time PCR analysis, YJCGT and YJYRS showed inhibitory effect on liver fibrogenesis by reducing associated gene expressions caused by MCD diet. Conclusion : YJCGT and YJSRS are considered to be possible candidates for the treatment of patients with NASH and/or liver fibrosis.

• Journal of Nutrition and Health
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• 제56권6호
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• pp.589-601
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• 2023

Purpose: Baicalein, a natural flavone found in herbs, exhibits diverse biological activities. Nonalcoholic steatohepatitis (NASH) is an irreversible condition often associated with a poor prognosis. This study aimed to evaluate the effects of baicalein on the development of NASH in mice. Methods: Male C57BL/6J mice were randomly divided into four groups. Three groups were fed a methionine-choline-deficient (MCD) diet to induce NASH and were simultaneously treated with baicalein (at doses of 50 and 100 mg/kg) or vehicle only (sodium carboxymethylcellulose) through oral gavage for 4 weeks. The control group was fed a methionine-choline-sufficient (MCS) diet without the administration of baicalein. Results: The baicalein treatment significantly reduced serum levels of alanine aminotransferase and aspartate aminotransferase, suggestive of reduced liver damage. Histological analysis revealed a marked decrease in nonalcoholic fatty liver activity scores induced by the MCD diet in the mice. Similarly, baicalein treatment at both doses significantly attenuated the degree of hepatic fibrosis, as examined by Sirius red staining, and hepatocellular death, as examined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Baicalein treatment attenuated MCD-diet-induced lipid peroxidation, as evidenced by lower levels of hepatic malondialdehyde and 4-hydroxynonenal, demonstrating a reduction in oxidative stress resulting from lipid peroxidation. Moreover, baicalein treatment suppressed hepatic protein levels of 12-lipoxygenase (12-Lox) induced by the MCD diet. In contrast, baicalein enhanced the activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Additionally, baicalein treatment significantly reduced hepatic non-heme iron concentrations and hepatic ferritin protein levels in mice fed an MCD diet. Conclusion: To summarize, baicalein treatment suppresses hepatic lipid peroxidation, 12-Lox expression, and iron accumulation, all of which are associated with the attenuation of NASH progression.

• Clinical and Experimental Pediatrics
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• 제49권2호
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• pp.187-191
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• 2006

목 적 : MCD는 항경련제에 반응하지 않는 난치성 간질의 중요한 원인으로 수술적 치료의 대상으로 고려되어지지만, 병변의 범위나 분포에 따라 제한적이고 치료효과에 있어서도 차이가 보고되고 있다. 케톤생성 식이요법은 최근까지 대부분의 연구들에서 뛰어난 간질 억제효과를 보고하고 있으나, MCD 병변을 보이는 난치성 간질을 대상으로 시행한 케톤생성 식이요법의 치료 효과에 대한 보고는 국내외적으로 지금까지 없는 상태로, 본 연구에서는 이 환자군들에 대해 간질 수술보다 덜 침습적인 치료법인 케톤생성 식이요법의 간질 억제효과를 알아보고자 하였다. 방 법 : 1998년 이후 난치성 간질로 케톤생성 식이요법을 시행하였던 소아 환아들 중 뇌 MRI상 MCD 소견을 보이는 30명을 대상으로 후향적 의무기록 고찰과 분석을 시행하였으며, 케톤 생성 식이요법 시행 후 경련의 감소효과를 분석하였다. 결 과 : 전체 대상 30명 환아들의 남녀비는 1 : 1.1이었고, 경련을 처음 시작한 연령은 평균 $2.0{\pm}2.9$세, 케톤생성 식이요법을 시작한 평균 연령은 $5.4{\pm}4.6$세, 케톤생성 식이요법을 시작할 때까지의 경련 지속기간은 평균 $3.5{\pm}3.3$년, 환아들의 추적 관찰기간은 평균 $29.0{\pm}21.0$개월이었다. MCD의 종류는 대뇌 피질 이형성증(cortical dysplasia)이 24명(80.0%)으로 가장 많았고, MCD의 분포는 일측 대뇌 반구에만 있는 경우가 23명(76.7%), 양측 대뇌 반구 모두에 병변이 있는 경우가 7명(23.3%)이었다. 케톤생성 식이요법에 의한 경련의 감소 정도는 전체 30명의 환아 중 9명(30.0%)에서 경련이 완전히 소실되었으며, 50% 이상 경련이 감소된 경우는 14명(46.7%)이었는데, 경련을 처음 시작한 연령이나 케톤생성 식이요법을 시작할 때까지의 경련 지속기간은 경련의 감소효과와 통계학적 유의성이 없었고, 케톤생성 식이요법을 시작한 나이가 어릴수록, 케톤생성 식이요법의 기간이 길수록 경련의 감소효과가 높은 경향을 나타내었으나 통계적 유의성은 없었으며, MCD의 분포에 따른 특별한 연관관계는 없었다. 결 론 : 케톤생성 식이요법이 MCD 소견을 동반하고 있어 수술적 치료가 고려되어지는 난치성 소아 간질 환아에서도 간질 수술의 여러 가지 제한적인 측면과 침습성을 고려해 볼 때 효과적인 치료 결과를 기대할 수 있을 것으로 판단되며, 아직까지 국내외적으로 MCD를 동반한 난치성 소아 간질 환아에 대한 케톤생성 식이요법의 효과에 대한 자료가 미미한 상태이므로 전향적인 대규모의 비교 연구 및 분석이 필요할 것으로 사료된다.

• Yonsei Medical Journal
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• 제59권9호
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• pp.1064-1071
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• 2018

Purpose: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. Materials and Methods: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. Results: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory ($TGF-{\alpha}$, $IL-1{\beta}$, IL-6) and profibrogenic cytokines ($TGF-{\beta}1$, COL1A1, ${\alpha}-SMA$) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. Conclusion: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

• 대한본초학회지
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• 제33권6호
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• pp.61-70
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• 2018

Objectives : Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of hepatic triglycerides (TG) that leads to inflammation and fibrosis. Crataegi Fructus ethanol extract (CE) is a korean traditional herb that used for digestive diseases. It has been investigated that CE has the effect that prevent hepatotoxicity caused by CCl4 or GaIN and regulate the inflammatory in several organs. However, a hypolipidemic effect of CF has not been reported. Methods : The purpose of this study is that examine the lipid accumulation inhibitory effect of CE on NAFLD. We checked the body and liver weight change of MCD-diet induced mice with/without administration of CE. The blood lipid levels of C57BL/6J mice were checked by biochemistry. Also we observed the liver histology of MCD-diet induced mice and investigate the molecular mechanisms in MCD-diet-induced NAFLD in C57BL/6J mice. Results : CE improved MCD-diet-induced lipid accumulation and TG and TC levels. Also, CE decreased hepatic lipogenesis such as SREBP-1, $C/EBP{\alpha}$, $PPAR{\gamma}$, ACC and FAS. Besides, we also found out that CE increased AMPK phosphorylation. These results indicated that CE has the same ability to activate AMPK and then reduce SREBP-1, and FAS expression, finally leading to inhibit hepatic lipogenesis and hepatic antioxidative ability. Conclusions : In this report, we found CE exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in MCD-diet induced NAFLD model. Therefore, CE extract may be active in the prevention of fatty liver.

• 한국약용작물학회지
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• 제28권4호
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• pp.276-286
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• 2020

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with multiple metabolic disorders. The medicinal plant Curcuma longa L. is widely distributed in Asia and has been used to treat a spectrum diseases in clinical practice. To date, there are inadequate reports of the effects of C. longa 50% EtOH extract (CE) on NAFLD. Therefore, in this study, we evaluate the CE on an NAFLD animal and elucidate the mechanism of action. Methods and Results: C57BL/6J mice fed a methionine-choline deficient diet (MCD) were treated with CE or milk thistle, and changes in inflammation and stetosis were assessed. Experimental animals were divided into six group (n = 10); Normal, MCD, MCD + CE 50 mg/kg/day (CE 50), MCD + CE 100 mg/kg/day (CE 100), MCD + CE 150 mg/kg/day (CE 150), and the Control, MCD + Milk thistle 150 mg/kg/day (MT 150). Body weight, liver weight, liver function, and histological changes were assessed in experimental animals. Quantitative real-time polymerase chain reaction and western blot analyses were performed on samples collected after 4 weeks of treatment. We observed that CE administration improved MCD-diet-induced lipid accumulation, and triglyceride (TG) and total cholesterol (TC) levels in serum. Treatment with CE also decreased hepatic lipogenesis through modulation of the sterol regulatory element binding protein-1 (SREBP-1), CCAAT-enhancer binding protein α (C/EBPα), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor γ (PPARγ) expresion. In addition, the use of CE increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the up-regulation of toll-like receptor (TLR)-2 and TLR-4 signaling and the production of inflammatory mediators. Conclusions: In this report, we observed that CE regulated lipid accumulation in an MCD dietinduced NAFLD model by decreasing lipogenesis. These data suggeste that CE could effectively protect mice against MCD-induced NAFLD, by inhibiting the TLR-2 and TLR-4 signaling cascades.

• 약학회지
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• 제56권2호
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• pp.99-107
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• 2012

The protective effect of AI-1367 (Alnus japonica extract) on liver injury was investigated. Primary rat hepatocyte intoxication was induced by tert-butyl hydroperoxide (tBH), carbon tetrachloride ($CCl_4$), or D-glactosamine (D-GalN). Liver injury was induced by $CCl_4$, D-GalN or MCD (methionine choline deficient)-diet in mouse. The cellular leakage of lactate dehyrogenase and cell viability followed by the treatment of hepatotoxicants were significantly improved by AI-1367 treatment at a concentration range of 5~50 ${\mu}g/ml$ for tBH, 5~50 ${\mu}g/ml$ for D-GalN, and 5~100 ${\mu}g/ml$ for $CCl_4$, respectively. Treatment with AI-1367 (20, 10, 5 mg/kg, p.o.) on liver injury induced by subcutaneous injection of $CCl_4$ or D-GalN reduced significantly the levels of aspartate transaminase and alanine transaminase in serum. Histological observations revealed that fatty acid changes, hepatocyte necrosis and inflammatory cell infiltration in $CCl_4$ (D-GalN)-induced liver injury was improved by administration of AI-1367. AI-1367 treatment (10, 5, 2.5 mg/kg, p.o.) also significantly recovered the body weight change and serum levels of aspartate transaminase, alanine transaminase and triglyceride in liver injury induced by MCD diet. From these results, AI-1367 shows protective effects against tBH, $CCl_4$, D-GalN, or MCD diet-induced hepatotoxicity in vitro or in vivo.

• 한국식품영양학회지
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• 제35권5호
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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.

• 한국식품영양과학회지
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• 제27권5호
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• pp.980-986
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• 1998

The effects of mungbean sprout juice on cadmium-induced hepatotoxicity in rats were investigated. Sprague-Dawley rats weighing about 90g were divided into 4 groups and raised for 6 weeks. ; control group(CON), mungbean sprouts juice-administered group(MSJ), cadmium-administered group(CAD) fed water containing 40 ppm cadmium chloride and mung bean sprouts juice and cadmium-administered group(MCD). The diet was supplied every day for the measurement of feed efficiency ratio(FER) and net weight gain was measured every 3 days. The activities of serum glutamic oxaloactic transaminase(GOT) and glutamic pyruvic transaminase(GPT), superoxide dimutase(SOD), catalase and glutathione peroxidase(GSH-Px) in the liver and the hepatic contents of glutathione were examined. The contents of Cd in liver and kidney of the rats were determined by using ICP(Inductively Coupled Plasma Emission Spectrophotometer). Growth rate and FER were decreased in CAD group, compared with CON group but the changes were not significant in MCD group. The activities of serum GOT and GPT, SOD, catalase and GSH-Px in the liver were increased by Cd administration, but the alterations were decreased by supplementation with mungbean sprouts juice. The level of glutathione decreased in CAD group(26.8$\pm$9.0mg/g liver), whereas it increased in MCD group(36.4$\pm$15.8mg gliver). The content of Cd in the liver and kidney in MCD group(9.57 ppm, 4.88 ppm) was decreased, compared with CAD group(12.81 ppm, 5.46 ppm). This result suggested that mungbean sprout juice has a lowering effect on the accumulation of Cd in the liver and kidney and it is believed that the juice has some protective effects to Cd-induced hepatotoxicity in rats, but the mechanism of these effects was obscure.