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Standardized Salvia miltiorrhiza Extract as a Therapeutic Candidate for the Treatment and Prevention of Non-alcoholic Steatohepatitis
표준화 단삼추출물에 의한 비알콜성 지방간염 치료 및 예방 효과에 관한 연구

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dc.contributor.advisor김영식-
dc.contributor.author이학성-
dc.date.accessioned2017-07-13T16:31:07Z-
dc.date.available2017-07-13T16:31:07Z-
dc.date.issued2015-02-
dc.identifier.other000000024832-
dc.identifier.urihttps://hdl.handle.net/10371/120030-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 제약학과, 2015. 2. 김영식.-
dc.description.abstractNon-alcoholic fatty liver disease (NAFLD) refers to a broad spectrum of liver damage, which ranges from simple steatosis or intracellular triglyceride accumulation to inflammation (non-alcoholic steatohepatitis-
dc.description.abstractNASH) fibrosis and cirrhosis. The aim of this study was to investigate the effect of standardized extract of Salvia miltiorrhiza (SME) on gene and protein expression of NASH-related factors in activated human hepatic stellate cells (HSC), and in mice with steatohepatitis induced by a methionine-choline deficient (MCD) diet. Male C57BL/6J mice were placed on an MCD or control diet for 8 weeks and SME (0, 0.1, 0.5 and 1 mg/kg body weight) was administered orally every other day for 4 or 6 weeks. HSCs from the LX-2 cell line were treated with transforming growth factor β-1 (TGF-β1) or TGF-β1 plus SME (0.1–10 μg/mL). To investigate the effect of SME on reactive oxygen species (ROS)-induced condition, LX-2 cells were treated with hydrogen peroxide (H2O2) or H2O2 plus SME (0.1–100 μg/mL). MCD administration for 12 weeks increased mRNA expression of tumor necrosis factor (TNF-α), TGF-β1, interleukin-1β (IL-1β), C-reactive protein (CRP), α-smooth muscle actin (α-SMA), type I collagen, matrix metalloproteinase-2 (MMP-2) and MMP-9. TGF-β1-induced LX-2 cells exhibited similar gene expression patterns. SME treatment significantly reduced the mRNA and protein expression of NASH-related factors in the mouse model and HSCs. Histopathological liver analysis showed improved NAFLD activity and fibrosis score in SME-treated mice. The in vivo studies showed that SME had a significant effect at low doses. These results suggest that SME might be a potential therapeutic candidate for treatment and prevention of NAFLD.-
dc.description.tableofcontentsABSTRACT .................................................................. i
CONTENTS ................................................................ iii
LIST OF FIGURES ....................................................... vi
LIST OF TABLES ....................................................... viii

1. INTRODUCTION ....................................................... 1
2. MATERIALS AND METHODS .................................... 12
2.1 Preparation of standardized extract of Salvia
miltiorrhiza ......................................................... 12
2.2 Stability analysis of tanshinone IIA by HPLC
.......................................................................... 13
2.3 Animals and Experimental protocol ....................... 13
2.4 Liver Histopathology ............................................ 16
2.4.1 NASH (NAFLD Activity Score) Evaluation ........... 16
2.4.2 Fibrosis evaluation and Measurement of collagen
distribution ..................................................... 16
2.5 Cell culture & Reagents ....................................... 17
2.6 Preparation of liver lysate .................................... 17
2.7 RNA isolation and Quantitative PCR ...................... 18
2.8 Enzyme-Linked Immunosorbent Assay (ELISA) .... 20
2.9 Intracellular ROS Activity ..................................... 20
2.10 Statistical analysis ............................................ 21
3. RESULTS AND DISCUSSION ................................... 22
3.1 Body Weight and Clinical Observations ................. 22
3.2 Liver Weight ....................................................... 24
3.3 Mortality ............................................................ 24
3.4 Histopathology Analysis ...................................... 27
3.5 Stability Test of Tanshinone IIA ............................ 36
3.6 Effect of SME on Hepatic TNF-α and Collagen I
Expression in NASH Induced by the MCD Diet in
Mice ................................................................. 41
3.7 Effect of SME on Hepatic mRNA Expression of NASH-
Related Specific Genes in the MCD Dietary Mouse
Model ............................................................... 43
3.8 Effect of SME on mRNA Expression of NASH-Related
Specific Genes in HSCs Induced by TGF-β1 ......... 46
3.9 Effect of SME on HSCs Induced by Oxidative
Stress .............................................................. 49
4. CONCLUSIONS ..................................................... 51
REFERENCES .......................................................... 52
ABSTRACT IN KOREAN ............................................ 59
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dc.formatapplication/pdf-
dc.format.extent2828946 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectSalvia miltiorrhiza-
dc.subjectnon-alcoholic steatohepatitis (NASH)-
dc.subjectmethionine-choline deficient (MCD)-
dc.subjecthepatic stellate cell (HSC)-
dc.subjectTGF-β1-
dc.subjectTNF-α-
dc.subjecttanshinone IIA-
dc.subject.ddc615-
dc.titleStandardized Salvia miltiorrhiza Extract as a Therapeutic Candidate for the Treatment and Prevention of Non-alcoholic Steatohepatitis-
dc.title.alternative표준화 단삼추출물에 의한 비알콜성 지방간염 치료 및 예방 효과에 관한 연구-
dc.typeThesis-
dc.contributor.AlternativeAuthorHak Sung Lee-
dc.description.degreeDoctor-
dc.citation.pagesviii, 61-
dc.contributor.affiliation약학대학 제약학과-
dc.date.awarded2015-02-
Appears in Collections:
College of Pharmacy (약학대학)Dept. of Manufacturing Pharmacy (제약학과)Theses (Ph.D. / Sc.D._제약학과)
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