• The Journal of Internal Korean Medicine
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• v.43 no.4
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• pp.643-655
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• 2022

Objective: To investigate the protective effects of Haeganjeon on a thioacetamide (TAA)-induced liver fibrosis mouse model and to determine the Haegan-jeon signaling pathway. Methods: Mice were randomly divided into 4 groups: Normal group (Nor), TAA-induced liver fibrosis group (Con), TAA-induced liver fibrosis group administered 50 mg/kg silymarin (S50), TAA-induced liver fibrosis group administered 200 mg/kg Haegan-jeon (H200). The liver fibrosis mouse model was established by intraperitoneal injection with TAA three times a week for 8 weeks. During the 8 weeks, mice were orally administered silymarin and Haegan-jeon every day. At the end of the study, serum was collected to measure the levels of AST, ALT, ammonia, and myeloperoxidase (MPO). Liver tissue was harvested and analyzed by western blotting and Masson's trichrome staining. Results: Administration of Haegan-jeon suppressed the increase in serum levels of AST, ALT, ammonia, and MPO due to TAA-induced liver fibrosis. Compared to the Con group, the H200 group showed increases in antioxidant-related factors (Nrf2, HO-1, catalase, and GPx-1/2) and decreases in inflammatory-related factors (NF-κB p65, p-IκB-α, Cox-2, iNOS, TNF-α, and IL-1β) in western blots. The H200 treatment inhibited the expression of α-SMA and Collagen I. Conclusions: Haegan-jeon showed a hepatoprotective effect induced by activation of antioxidant-related factors, such as Nrf2, and it regulated the inflammation response by suppression of NF-κB.

• Journal of Nutrition and Health
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• v.54 no.2
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• pp.224-237
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• 2021

Purpose: Paeonia Radix Alba is a traditional herbal medicine used to treat the liver and the spleen. Many studies have reported that Paeonia Radix Alba extract (PR) affects liver injury, but there has been no study on liver injuries induced by thioacetamide (TAA). Therefore, we aimed at evaluating the effect of PR on a TAA-induced acute liver injury (ALI) model. Methods: The antioxidant activity of PR was assayed by the content of total polyphenol, total flavonoid, 1,1-diphenyl-2'-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonicacid) (ABTS) radical scavenging activities in vitro test. ALI was induced via-intraperitoneal injection of TAA (200 mg/kg body weight) for three consecutive days. Also, silymarin (100 mg/kg body weight) and PR (100 or 200 mg/kg body weight) were administered at 1 hours 30 minutes prior to TAA treatment. The levels of ammonia, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were analyzed using an assay kit. The expressions of antioxidant proteins including Nrf2, Keap1, HO-1, SOD, catalase, and GPx-1/2 and oxidative stress-related proteins including NOX2, p47^phox, and p22^phox were evaluated by the western blot analysis. Results: PR showed excellent antioxidant activity in vitro. TAA administration increased the levels of ammonia, GOT, and GPT in the ALI control group compared to the normal group, whereas it was significantly reduced by PR pretreatment. Moreover, NADPH oxidase protein expressions were upregulated after TAA treatment, while the elevated expressions were inhibited by PR pretreatment. The expressions of antioxidant protein were downregulated in the ALI control group, whereas Nrf2 activation in the PR group was accompanied by increased levels of antioxidant enzymes. Conclusion: PR administration increased the antioxidant enzymes via activation of the Keap1/Nrf2 pathway and inhibited the protein levels of NADPH oxidase factors. Taken together, these results showed that PR treatment may be considered to ameliorate acute liver injury induced by TAA.

• Korean Journal of Clinical Laboratory Science
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• v.43 no.4
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• pp.194-204
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• 2011

This study was carried out to compare the histopathological differences of liver lesions in carbon tetrachloride ($CCI_4$), dimethylnitrosamine (DMN), thioacetamide (TAA) and bile duct ligation (BDL)-induced rats. $CCl_4$, DMN and TAA were administered intraperitoneally and conducted bile duct ligation for 4 weeks to induce hepatic fibrosis. Indices of liver cell injury (steatosis, hydropic degeneration, bile duct hyperplasia, hemorrhage & hemosiderin deposition), the extent of liver fibrosis (fibrotic area) and the rate of regeneration (number of PCNA-positive cells) were investigated in each group. Liver tissues were stained with hematoxylin-eosin (HE), sirius red, prussian blue and immunostained with ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), proliferative cell nuclear antigen (PCNA), and quantified using a computerized image analysis system. Liver cell steatosis was significantly increased in $CCl_4$ and TAA groups, and hydropic degeneration and bile duct hyperplasia were significantly increased in TAA and BDL groups when compared with that in normal control, respectively. Fibrosis area was significantly increased in all four groups, especially in $CCl_4$ group. Correlation between ${\alpha}$-SMA and TGF-${\beta}1$ expressions in four groups was good. Hemorrhage area in liver parenchyma was significantly increased in DMN group only when compared with that in normal control, while hemosiderin deposition area was significantly increased in TAA and BDL groups as well as DMN group. The Number of PCNA-positive cells was significantly increased in all four groups, especially in TAA group. These results indicate that the duration and methods of hepatotoxic drug treatment are very important factors to make plans for animal experimentation on the induction of hepatic fibrogenesis in rats.

• Nutrition Research and Practice
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• v.11 no.6
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• pp.470-478
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• 2017

BACKGROUND/OBJECTIVE: Orostachys japonicus A. Berger (Crassulaceae) has been used in traditional herbal medicines in Korea and other Asian countries to treat various diseases, including liver disorders. In the present study, the anti-fibrotic effects of O. japonicus extract (OJE) in cellular and experimental hepatofibrotic rat models were investigated. MATERIALS/METHODS: An in vitro hepatic stellate cells (HSCs) system was used to estimate cell viability, cell cycle and apoptosis by MTT assay, flow cytometry, and Annexin V-FITC/PI staining techniques, respectively. In addition, thioacetamide (TAA)-induced liver fibrosis was established in Sprague Dawley rats. Briefly, animals were divided into five groups (n = 8): Control, TAA, OJE 10 (TAA with OJE 10 mg/kg), OJE 100 (TAA with OJE 100 mg/kg) and silymarin (TAA with Silymarin 50 mg/kg). Fibrosis was induced by treatment with TAA (200 mg/kg, i.p.) twice per week for 13 weeks, while OJE and silymarin were administered orally two times per week from week 7 to 13. The fibrotic related gene expression serum biomarkers glutathione and hydroxyproline were estimated by RT-PCR and spectrophotometry, respectively, using commercial kits. RESULTS: OJE (0.5 and 0.1 mg/ mL) and silymarin (0.05 mg/mL) treatment significantly (P < 0.01 and P < 0.001) induced apoptosis (16.95% and 27.48% for OJE and 25.87% for silymarin, respectively) in HSC-T6 cells when compared with the control group (9.09%). Further, rat primary HSCs showed changes in morphology in response to OJE 0.1 mg/mL treatment. In in vivo studies, OJE (10 and 100 mg/kg) treatment significantly ameliorated TAA-induced alterations in levels of serum biomarkers, fibrotic related gene expression, glutathione, and hydroxyproline (P < 0.05-P < 0.001) and rescued the histopathological changes. CONCLUSIONS: OJE can be developed as a potential agent for the treatment of hepatofibrosis.

• The Korea Journal of Herbology
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• v.33 no.1
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• pp.47-55
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• 2018

Objectives : The current study is to evaluate the hepatoprotective effect of youngyanggak-san (YGS) on thioacetamide (TAA)-induced acute liver injury in rats. Methods : YGS is composed of Glycyrrhizae Radix, Asiasari Radix, Cimicifugae Rhizoma, Saigae Tataricae Cornu. While N-YGS (non-youngyanggak-san) doesn't include Saigae Tataricae Cornu. Two samples were administrated TAA together for 3 days. Thirty-six rats were divided into four groups. Rats except for the normal group were received TAA (200 mg/kg of body weight, I.P) were divided into three groups (n=9/group) : Group 1 (TAA only), Group 2 (TAA + 200 mg/kg YGS) and Group 3 (TAA + 200 mg/kg N-YGS). Acute liver damage confirmed using histological examination, The factors associated with oxidative stress and liver function activity measured in serum. Also, expressions of inflammation related proteins were investigated by western blot analysis. Results : Oxidative stress factors such as ROS and $ONOO^-$ in the Group 2 was manifested by a significant rise compared with Group 1. YGS markedly decreased the elevated ROS and $ONOO^-$. Furthermore, YGS significantly reduced the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) The nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) activation induced by TAA led to increase both inflammatory mediators and cytokines. While YGS administration remarkably suppressed such the overexpression. In addition, the histopathological analysis showed that the liver tissue lesions were improved obviously in YGS treatment. Conclusion : YGS provided a hepatoprotective effect on acute liver damage through the suppression of oxidative stress. Especially, this effect enhanced markedly when Saigae Tataricae Cornu is included.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.973-978
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• 2003

A polymeric film composed of Carbopol, Poloxamer and hydroxypropyl methylcellulose was prepared to develop a buccal patch and the effects of composition of the film on adhesion time, swelling ratio, and dissolution of the film were studied. The effects of plasticizers or penetration enhancers on the release of triamcinolone acetonide (TAA) were also studied. The hydrogen bonding between Carbopol and Poloxamer played important role in reducing swelling ratio and dissolution rate of polymer film and increasing adhesion time. The swelling ratio of the composite film was significantly reduced and the adhesion time was increased when compared with Carbopol film. As the ratio of Poloxamer to hydroxypropyl methylcellulose increased from 0/66 to 33/33, the release rate of TAA decreased. However, no further significant decrease of release rate was observed beyond the ratio of 33/33. The release rate of TAA in the polymeric film containing polyethylene glycol 400, a plasticizer, showed the highest release rate followed by triethyl citrate, and castor oil. The release rate of TAA from the polymeric film containing permeation enhancers was slower than that from the control without enhancers. Therefore, these observations indicated that a preparation of a buccal patch is feasible with the polymeric film composed of Cabopol, Poloxamer and hydropropyl methylcellulose.

• The Journal of Internal Korean Medicine
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• v.42 no.6
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• pp.1223-1236
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• 2021

Objectives: The aim of the current study was to investigate the effect of Sosiho-tang on thioacetamide (TAA)-induced liver fibrosis in mice and to elucidate its underlying mechanisms. Methods: The mice were divided into 4 groups: Normal mice (Normal), TAA-induced control mice (Control), TAA-induced and silymarin-treated (50 mg/kg) mice (Silymarin), and TAA-induced and Sosiho-tang treated (200 mg/kg) mice (SSHT). Liver fibrosis was induced via intraperitoneal injection of TAA three times a week for 8 weeks. Silymarin and Sosiho-tang were concomitantly administered for 8 weeks. Serum and liver tissues were then collected and the anti-oxidant and inflammatory protein levels in the liver tissues were evaluated using western blotting. Results: SSHT administration significantly reduced the levels of AST, ALT, ammonia, and MPO in the serum. SSHT also significantly down-regulated liver NADPH oxidase and regulated the Nrf2/Keap1 signaling pathway. SSHT treatment downregulated the liver NF-κB levels and suppressed inflammatory cytokines. SSHT treatment also decreased bile acid-related factors, such as CYP7A1 and NTCP, and fibrosis-related factors, such as α-SMA and Collagen I. Conclusions: Taken together, these data suggest that SSHT administration suppressed the progression of liver fibrosis by activating the Nrf2/Keap1 pathway and inhibiting NF-κB.

• Journal of Korean Foot and Ankle Society
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• v.26 no.3
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• pp.111-117
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• 2022

Despite the lack of evidence-based standard guidelines to select the best surgical treatment option for end-stage ankle osteoarthritis, the rate of total ankle arthroplasty (TAA) is increasing rapidly relative to ankle arthrodesis (AA) with the development of implant designs and surgical techniques. Physicians and patients would benefit from a more comprehensive understanding of the differences in postoperative pain relief, functional improvement, the rates of complication or reoperation, and restoration of gait ability and sports activity. This paper overviews the current consensus on indications and contraindications for TAA and provides a literature review on a comparison of the clinical and functional results between TAA and AA.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.252-260
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• 2007

As it is needed to assay possible feasibility of extrapolation between in vivo and in vitro systems and to develop a new in vitro method for toxicity testing, we investigated global gene expression from both animal and cell line treated with thioacetamide (TAA) and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with TAA and sacrificed at 6 and 24 h. For in vitro study, TAA was administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose TAA-treated group, there was centrilobular necrosis (in vivo) and cellular toxicity with an elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified several common pathways existed between in vivo and in vitro system such as glutathione metabolism, bile acid biosynthesis, nitrogen metabolism, butanoate metabolism for hepatotoxicty caused by TAA. Our results suggest it may be feasible to develop toxicogenomics biomarkers by comparing in vivo and in vitro genomic profiles specific to TAA for application to prediction of liver toxicity.

• Journal of Korean Foot and Ankle Society
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• v.25 no.3
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• pp.111-116
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• 2021

Purpose: Variations in the preferred conservative and operative treatment methods for ankle arthritis may be observed in the practice of orthopedic surgeons. This study is based on the Korean Foot and Ankle Society (KFAS) member survey and aims to report the current trend and changes in the management of ankle arthritis over the last few decades. Materials and Methods: A web-based questionnaire containing 24 questions was sent to all KFAS members in July 2021. The questions were mainly related to the preferred techniques and clinical experience in osteotomy, arthrodesis, and total ankle arthroplasty (TAA) for patients with ankle arthritis. Results: Sixty-three out of 550 surgeons (11.5%) responded to the survey. The responses to 6 out of the total of 24 questions (25.0%) achieved the levels needed to reflect a tendency. Answers that showed a tendency were related to the following: a surgical approach for arthrodesis (anterior approach), use of auto-bone graft for arthrodesis (iliac bone), a nonunion rate of more than 10% following arthrodesis, main reason related to unsatisfactory results after arthrodesis (nonunion or delayed union), the main reason to change total ankle prosthesis (unstable supply of prosthesis), the unusualness of revision TAA and conversion of fusion to TAA. Diversity was found in several aspects of treatment (degree of experience and satisfaction in supramalleolar osteotomy, fixation method for arthrodesis, preferred TAA prosthesis and longevity, degree of experinece, annual number of TAA operation. Conclusion: This study proposes updated information with regard to the current trends in the management of ankle arthritis in Korea. Both consensus and variations in the approach to patients with ankle arthritis were identified through this survey. With an increasing preference for TAA, the need for the development of a prosthesis optimized for Koreans and a stable supply of prostheses were the suggestions made by the study.