• Herbal Formula Science
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• v.24 no.4
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• pp.311-321
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• 2016

Chronic or acute alcohol abuse often leads to liver injury associated with alcoholic hepatitis, liver fibrosis, cirrhosis, and liver cancer. In addition to the liver, alcohol abuse also induces a variety of other tissue injuries including pancreatitis, cardiomyopathy, neurotoxicity and muscle loss. Chronic skeletal muscle myopathy, independent of peripheral neuropathy, is well recognised in alcoholic patients. Several mechanisms may be involved in the pathogenesis of alcoholic myopathy. Ethanol is a potent inhibitor of muscle protein synthesis. Gastrocnemius and plantaris muscles are Type II fiber-predominant and usually considered representative of the musculature as a whole. Whereas, soleus muscle is Type I fiber predominant. Shihosogan-san is a traditional Korean medicine that is widely employed to treat indigestion and liver diseases. Muscle diseases are often related to liver diseases and conditions. We therefore tested the hypothesis that treatment with Shihosogan-san could ameliorate the ethanol-induced changes in muscle protein synthesis. Young male Sprague-Dawley rats were orally given 25% ethanol (5ml/kg, body weight) daily with Ethanol for 28 days. Normal group was similarly administrated with saline. In Shihosogan-san treated group, rats were orally administrated Shihosogan-san extract, and rats of EtOH group were given with the vehicle only. After 4 week, the morphology of gastrocnemius and plantaris muscles were assessed by hematoxylin and eosin staining. For comparative purposes, liver function was also investigated. The muscles from rats of EtOH group displayed a significant reduction in average cross section area compared to Normal group. Shihosogan-san treated group had increased fiber compared to the EtOH group. Moreover, Shihosogan-san treated group compared with EtOH group showed significantly decreased pro-apoptotic BAX expression and increased anti-apoptotic Bcl-2 expression. In conclusion, Shihosogan-san extract showed ameliorating effects on chronic alcohol toxicity in skeletal muscle.

• Journal of Applied Biological Chemistry
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• v.59 no.3
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• pp.265-271
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• 2016

Recently, liver damage contributes to big percentage of the morbidity and mortality rates worldwide. Excessive intake of alcohol is one of the major causes of liver injury. When liver injury is repeated and becomes chronic, it leads to development of fibrosis and cirrhosis. In the liver, TGF-${\beta}$ is a profibrogenic cytokine, which participates in various critical events cause liver fibrosis. Seahorse (Hippocampus abdominalis) is a common traditional Chinese medicine and has been widely used for centuries. Seahorse has been known to have a variety of bioactivities, such as anti-oxidant, anti-fatigue, and anti-tumor. Peptide is one of the main compounds of seahorse. In this study, we isolated enzymatic hydrolysate from seahorse H. abdominalis by alcalase hydrolysis and investigated the effect of the hydrolysate on liver injury. In the present in vitro studies, the hydrolysate increases cell viability of Chang cells and protects Huh7 cells from ethanol toxicity. In addition, the hydrolysate inhibits TGF-${\beta}$-induced responses. In vivo studies show that the pretreatment of hydrolysate reduces alcohol-induced increases of serum Glutamic oxaloacetic acid transaminase and Glutamic pyruvate transaminase activities and increases liver weight and body weight. These results suggest that seahorse may have a hepatoprotective effect.

• The Journal of Korean Medicine
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• v.18 no.1
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• pp.480-498
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• 1997

This study was to investigate the protective and anticirrhotic effects of Mockhyangjokisan and Haewooljoweetang on the liver cirrhosis or fibrosis induced by prolonged bile duct ligation; a new experimental model for cirrhosis and the intraperitoneal injection of dimethylnitrosamine in the rat. The development of fibrosis or cirrhosis and its inhibition by the two prescriptions were examined by the chemical analysis of AST, ALT, and hydroxyproline. The results obtained were as follows. 1. The increase of serum asparate aminotransferase induced by bile duct ligation was inhibited by the administration of Mockhyangjokisan and Haewooljoweetang extract. 2. The increase of serum alanine aminotransferase induced by bile duct ligation was inhibited by the administration of Mockhyangjokisan and Haewooljoweetang extract. 3. The increased level of serum AST and AL T induced by the intraperitoneal injection of dimethylnitrosamine was inhibited by the administration of Mockhyangjokisan and Haewooljoweetang extract. 4. The increasing level of hydroxyproline volume in the damaged liver tissues in the rat was decreased by the oral administration of Mockhyangjokisan and Haewooljoweetang extract. But there were no significant differences in the inhibition rate between the two experimental groups.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.1
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• pp.63-71
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• 2020

Purpose: Autoimmune hepatitis (AIH) is a chronic disease that may lead to cirrhosis. The immunopathogenesis of AIH is not fully understood and it mainly involves T-cell mediated mechanism. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that promotes T cell response and its polymorphism may serve as a severity marker of AIH. No previous study has considered investigating MIF polymorphism in children with AIH. Methods: Forty-two children with definite diagnosis of AIH were enrolled along with 100 age and sex matched controls. All participants were tested for polymorphism at -173GC (rs755622) of MIF gene. All patients received the standard protocol of steroid plus azathioprine to achieve remission. Liver biopsy was performed at time of diagnosis for all patients and only 18 of them underwent a second biopsy after treatment. Results: No statistically significant differences in the frequency of the genotypes GG and GC or in allele distribution were found in both patient and control groups (p=0.590, 0.640 respectively). Initial alanine aminotransferase (ALT) levels at the time of presentation was significantly higher in the GC group than GG group (p=0.020). GC genotype significantly correlated with disease relapse (r=0.41, p=0.007). Regression of necroinflammation and the fibrosis score in the second liver biopsy was statistically significant in the GG group (p<0.0001, p=0.010 respectively). Conclusion: MIF -173GC polymorphism is associated with clinically significant markers of pediatric AIH, including increased initial serum ALT levels, may help predict necroinflammatory/fibrosis regression effectively, following immunosuppressive treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.637-642
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• 2014

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

• The Journal of Internal Korean Medicine
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• v.26 no.4
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• pp.853-863
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• 2005

Object : This study was performed to investigate the anti-fibrogenic effect of Artemisiae Capillaris Herba(ACH) on cultured rat hepatic stellate cells. Methods : Hepatic Stellate Cells were obtained from a 350gm Sprague-Dawley rat by tissue perfusion system, and the cells for the study were selected after 3 passages of culture on non-coated plastic culture dishes which enable the cells to activate, thus producing collagens in the cell media. Cells were treated with various concentrations of Artemisia Capillaris Herba(ACH) extract powder for 24 or 48 hours. After the treatment, Soluble collagen, procollagen levels and the mRNA of the procollagen type I C were measured by using assay kit and RT-PCR method. Results : Procollagen production by the hepatic stellate cells decreased after the treatment in a time-dependent dose-dependent manner. The mRNA expression decreased consistently with the volume of the secreted procollagen which indicates the herb hat inhibitory effect on fibrogenesis of the liver by regulating one of the fibrosis associated genes in transcription. Conclusion : These results suggest that ACH is beneficial in the treatment of cirrhotic patients as well as for the patients with chronic hepatitis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4803-4812
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• 2015

Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.93-106
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• 2005

Objectives : The aim of this study is to characterize the effect of Chungganhaeju-tang on $TGF-{\beta}l$-induced hepatic fibrosis. Materials and Methods : mRNA and protein expression levels of $TGF-{\beta}l$ in Chungganhaeju-tang treated HepG2 cells were compared to untreated cells using quantitative RT-PCR and ELISA assay, respectively. mRNA expression levels of the $TGF-{\beta}l$ signaling pathway genes $(T{\beta}R-I,\;T{\beta}R-II,\;Smad2,\;Smad3,\;Smad4,\;and\;PAI-1)$ and fibrosis-associated genes (CTGF, fibronectin, and collagen type $l{\alpha}$) were evaluated by quantitative RT-PCR. The effect of Chungganhaeju-tang on cell proliferation of T3891 human fibroblast was evaluated using $[^3H]Thymidine$ Incorporation Assay. Results : Inhibition of $TGF-{\beta}l$ mRNA expression and protein production was observed with treatment of Chungganhaeju-tang and seen to be dose and time dependent. Whereas $TGF-{\beta}l$-mediated induction of PAI-1 was suppressed with treatment of Chungganhaeju-tang, expression of the $TGF-{\beta}l$ signaling pathway genes such as $T{\beta}R-I$, $T{\beta}R-II$, Smad2, Smad3, and Smad4 was not affected. With treatment of Chungganhaeju-tang, inhibition of $TGF-{\beta}l$-induced cell proliferation of T3891 human fibroblast was observed, as well as abrogation of $TGF-{\beta}l$-mediated transcriptional up-regulation of CTGF, fibronectin, and collagen type $I{\alpha}$. Conclusion : This study strongly suggests that the liver cirrhosis-suppressive activity of Chungganhaeju-tang may be derived at least in part from its inhibitory effect on $TGF-{\beta}l$ functions, such as blockade of $TGF-{\beta}l$ stimulation of fibroblast cell proliferation and fibrosis-related gene expression as well as expression of $TGF-{\beta}l$ itself.

• The Journal of Internal Korean Medicine
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• v.30 no.1
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• pp.74-84
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• 2009

Objectives : This study was performed to investigate the anti-fibrogenic effect of Injinchunggan-tang on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells(HSC-T6) were treated with various concentrations of Injinchunggan-tang extract for 24, 48, and 72 hours. The extraction was done with distilled water. After the treatment, cell viability, proliferation, procollagen levels and the mRNA of the TIMP-1, TIMP-2, and ASMA were measured by using MTT assay. BrdU assay, procollagen type I C-peptide EIA kit and RT-PCR. Results : The proliferation, mRNA expression and synthesis of collagen of the hepatic stellate cells were inhibited by Injinchunggan-tang treatment in a dose-dependent manner. This indicates the prescription has inhibitory effect on fibrogenesis of the liver by regulating the fibrogenesis associated genes in transcription. Cell viability was inhibited in time- and dose-dependent manners. It seemed that the drug should be used with sufficient dose to acquire treatment effect. Conclusion : These results suggest that Injinchunggan-tang is beneficial in the treatment of cirrhotic patients as well as for the patients with chronic hepatitis.

• Korean Journal of Food Science and Technology
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• v.41 no.5
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• pp.597-601
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• 2009

Activation of hepatic stellate cells (HSCs) is known to be responsible for hepatic fibrosis and cirrhosis. When round-shape quiescent HSCs go to activation by liver injury, production of extracellular matrix is increased, and its shape becomes myofibroblast-like shape. The activated HSCs are characterized by the high rate of proliferation and the increased production of extracellular matrix. One way of the regeneration of activated HSCs is an apoptosis induction followed by removing the activated myofibroblast-like cells. The effect of extract of Terminalia chebula Retz. (TCE) on cytotoxicity was evaluated using the rat primary hepatocyte, HepG2 and T-HSC/Cl-6 by incubating these cells with TCE up to the dose of $1,000{\mu}g/mL$. At the maximum dose of TCE, no cytotoxicity was found on primary hepatocyte and HepG2, but cytotoxic effect of TCE was found on activated HSCs, and T-HSC/Cl-6 in a U-shaped dose-response manner with the highest effect at $500{\mu}g/mL$ of TCE. Finally, we confirmed the occurrence of apoptotic cell death by annexin-V/PI double staining. The population of annexin-V positive cells was increased in a dose dependent manner.