Inaugural dissertation (Ph. D.)--Friedrich-Wilhelms-Universität zu Berlin, 1933. / Cover title. Bibliography: p. 43-44.

Thesis (Ph. D.)--University of Michigan, 2008. / Includes bibliographical references. Also available in PDF format via the Internet.

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Yip, Ka Yan. / "August 2011." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 87-113). / Abstracts in English and Chinese. / Acknowledgement --- p.III / Abstract --- p.V / 論文摘要 --- p.VI / Table of Contents --- p.VII / List of Figures --- p.IX / List of Abbreviations --- p.XI / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Hepatocellular carcinoma --- p.1 / Chapter 1.1.1 --- Overview --- p.1 / Chapter 1.1.2 --- Risk factors --- p.3 / Chapter 1.1.3 --- Treatment ofHCC --- p.12 / Chapter 1.2 --- Berberine - a compound derived from Traditional Chinese Medicine --- p.15 / Chapter 1.2.1 --- Traditional Chinese Medicine --- p.15 / Chapter 1.2.2 --- Berberine --- p.16 / Chapter 1.3 --- Cell cycle --- p.18 / Chapter 1.3.1 --- An Overview of cell cycle --- p.18 / Chapter 1.3.2 --- Cell cycle and carcinogenesis --- p.18 / Chapter 1.4 --- Molecular mechanism of apoptosis --- p.20 / Chapter 1.4.1 --- Overview of apoptosis --- p.20 / Chapter 1.4.2 --- Caspases cascade --- p.22 / Chapter 1.4.3 --- Bcl-2 family --- p.24 / Chapter 1.5 --- Apoptosis as a target of cancer therapy --- p.26 / Chapter 1.6 --- Aims of study --- p.27 / Chapter Chapter 2 --- Materials and Methods --- p.28 / Chapter 2.1 --- Cell culture and treatment --- p.28 / Chapter 2.1.1 --- Cell lines --- p.28 / Chapter 2.1.2 --- Berberine --- p.29 / Chapter 2.1.3 --- Chemicals and reagents --- p.29 / Chapter 2.1.4 --- Preparation of solutions --- p.29 / Chapter 2.1.5 --- Procedures --- p.31 / Chapter 2.2 --- Apoptosis detection by FITC Annexin V and PI co-staining --- p.33 / Chapter 2.2.1 --- Chemicals and reagents --- p.33 / Chapter 2.2.2 --- Procedures --- p.33 / Chapter 2.3 --- Gene expression in Berberine-induced apoptotic cells --- p.35 / Chapter 2.3.1 --- Chemicals and Reagents --- p.35 / Chapter 2.3.2 --- Procedures --- p.35 / Chapter 2.4 --- Protein expression in Berberine-induced apoptotic cells --- p.38 / Chapter 2.4.1 --- Chemicals and Reagents --- p.38 / Chapter 2.4.2 --- Preparation of solution --- p.39 / Chapter 2.4.3 --- Procedures --- p.41 / Chapter 2.5 --- Caspase cascade studies in berberine-induced apoptosis --- p.43 / Chapter 2.5.1 --- Chemicals and reagents --- p.43 / Chapter 2.5.2 --- Procedures --- p.43 / Chapter 2.6 --- Cell cycle study in berberine-induced apoptotic cells --- p.44 / Chapter 2.6.1 --- Chemicals and Reagents --- p.44 / Chapter 2.6.2 --- Preparation of solutions --- p.44 / Chapter 2.6.3 --- Procedures --- p.44 / Chapter Chapter 3 --- Results --- p.46 / Chapter 3.1 --- Berberine induces apoptosis in hepatocellular cells --- p.46 / Chapter 3.2 --- Gene expression in Berberine-induced apoptotic cells --- p.53 / Chapter 3.3 --- Caspase cascade studies in berberine-induced apoptosis --- p.58 / Chapter 3.4 --- Protein expression in Berberine-induced apoptotic cells --- p.62 / Chapter 3.5 --- Berberine caused G1 cell cycle arrest in HCC cell lines --- p.65 / Chapter Chapter 4 --- Discussion --- p.76 / References --- p.87

Wu, Hoi Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 92-104). / Abstracts in English and Chinese. / Thesis/ Assessment Committee --- p.i / Declaration --- p.ii / Acknowledgments --- p.vi / Table of Content --- p.vii / List of Abbreviations --- p.x / List of Figures --- p.xiv / List of Tables --- p.xv / Chapter 1. --- Literature Review --- p.1 / Chapter 1.1 --- Introduction of diabetes mellitus --- p.1 / Chapter 1.1.1 --- Definition and prevalence --- p.1 / Chapter 1.1.2 --- Diagnosis and classification --- p.2 / Chapter 1.1.3 --- Symptoms and complications --- p.4 / Chapter 1.1.4 --- Cause and risk factors --- p.5 / Chapter 1.1.5 --- Prevention and treatment --- p.9 / Chapter 1.2 --- The role of adipose tissue in pathophysiology of T2DM --- p.10 / Chapter 1.2.1 --- Randle's glucose-fatty acid hypothesis --- p.11 / Chapter 1.2.2 --- Ectopic fat storage hypothesis --- p.12 / Chapter 1.2.3 --- Adipose tissue as an endocrine organ --- p.13 / Chapter 1.2.4 --- Low-grade inflammation --- p.15 / Chapter 1.2.5 --- Endoplasmic reticulum (ER) stress --- p.17 / Chapter 1.3 --- Use of berberine in the treatment of T2DM --- p.18 / Chapter 1.3.1 --- Efficacy of berberine in treating diabetes --- p.18 / Chapter 1.3.2 --- Berberine on glucose and lipid metabolism of animals --- p.19 / Chapter 1.3.3 --- Inhibition of adipogenesis --- p.20 / Chapter 1.3.4 --- Activation of AMP-Activated Protein Kinase (AMPK) --- p.20 / Chapter 1.3.5 --- Mitochondrial inhibition --- p.21 / Chapter 1.4 --- Introduction of proteomics --- p.21 / Chapter 1.4.1 --- Why proteomics? --- p.22 / Chapter 1.4.2 --- Gel-based proteomics: Two-Dimensional Gel Electrophoresis --- p.23 / Chapter 1.4.3 --- Gel-free proteomics --- p.25 / Chapter 1.4.4 --- Mass spectrometry --- p.26 / Chapter 1.4.5 --- Proteomics as tool for diabetes research --- p.27 / Chapter 1.5 --- Objectives and significance --- p.32 / Chapter 2. --- Materials and Methods --- p.34 / Chapter 2.1 --- Drug preparation --- p.34 / Chapter 2.2 --- Animal experiment --- p.34 / Chapter 2.3 --- Comparison of proteome of visceral white adipose tissue: obese db/db micevs lean m+/db mice and BBR-treated vs control db/db mice --- p.36 / Chapter 2.3.1 --- Protein sample preparation from adipose tissue --- p.36 / Chapter 2.3.2 --- Protein quantitation --- p.37 / Chapter 2.3.3 --- 2D Gel electrophoresis --- p.37 / Chapter 2.3.4 --- Image analysis --- p.39 / Chapter 2.3.5 --- In-gel digestion and MALDI-ToF MS --- p.39 / Chapter 2.4 --- Cell culture experiment --- p.40 / Chapter 2.5 --- Oil Red O staining --- p.42 / Chapter 2.6 --- Glycerol determination --- p.42 / Chapter 2.7 --- Comparison of proteomes of BBR-treated and control 3T3-L1 adipocytes..… --- p.43 / Chapter 2.7.1 --- Protein sample preparation from 3T3-L1 cells --- p.43 / Chapter 2.7.2 --- Protein quantitation --- p.43 / Chapter 2.7.3 --- 2D Gel electrophoresis --- p.44 / Chapter 2.7.4 --- Image analysis --- p.44 / Chapter 2.7.5 --- In-gel digestion and MALDI-ToF MS --- p.44 / Chapter 2.8 --- Western Immunoblotting --- p.44 / Chapter 2.8.1 --- Protein sample preparation of BBR-treated and control 3T3-L1 --- p.44 / Chapter 2.8.2 --- SDS-PAGE --- p.44 / Chapter 2.8.3 --- Protein blotting --- p.45 / Chapter 2.8.4 --- Membrane blocking and antibody incubations --- p.45 / Chapter 2.8.5 --- Detection of Proteins --- p.46 / Chapter 2.9 --- Statistical analysis --- p.46 / Chapter 3. --- Results --- p.47 / Chapter 3.1 --- Comparison of total protein profiles of visceral adipose tissue of obese db/db and lean m+/db mice --- p.47 / Chapter 3.2 --- Effect of berberine on glucose metabolism of obese db/db mice --- p.53 / Chapter 3.3 --- Comparison of the protein profiles of visceral adipose tissue of BBR-treated and control db/db mice --- p.55 / Chapter 3.4 --- Effect of berberine treatment on 3T3-L1 adipocytes --- p.61 / Chapter 3.4.1 --- Berberine treatment inhibited intracellular triglyceride accumulation in both mature and pre-mature 3T3-L1 adipocytes --- p.61 / Chapter 3.4.2 --- Berberine treatment enhanced lipolysis in mature 3T3-L1 adipocytes but inhibited lipolysis in pre-mature 3T3-L1 adipocytes --- p.65 / Chapter 3.4.3 --- Color change in culture media after berberine treatment --- p.65 / Chapter 3.4.4. --- Comparison of protein profiles between berberine-treated and control 3T3-L1 adipocytes --- p.67 / Chapter 3.4.5 --- Western blotting --- p.73 / Chapter 4. --- Discussion --- p.75 / Chapter 4.1 --- Comparison of total protein profiles of visceral adipose tissue of obese db/db and lean m+/db mice --- p.75 / Chapter 4.2 --- "Berberine lowers body weight, reduces fasting blood glucose level and improves glucose-lowering ability of db/db mice" --- p.78 / Chapter 4.3 --- Comparison of the protein profiles of visceral adipose tissue of BBR-treated and control db/db mice --- p.79 / Chapter 4.4 --- Berberine inhibited lipid accumulation in mature and pre-mature 3T3-L1 adipocytes --- p.84 / Chapter 4.5 --- Berberine enhanced lipolysis in mature 3T3-L1 adipocytes but inhibited lipolysis in pre-mature 3T3-L1 adipocytes --- p.84 / Chapter 4.6 --- Comparison of the protein profiles of BBR-treated and control 3T3-L1 adipocytes --- p.85 / Chapter 4.7 --- Western blotting --- p.88 / Chapter 4.8 --- General discussion --- p.89 / Chapter 5. --- References --- p.92

Thesis (Ph. D.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 132-147). Also available on the World Wide Web.

Herbs have been used for many centuries in diverse civilizations for the treatment of heart disease. Only a few natural supplements claim to have direct cardiovascular actions including hawthorn (Crataegus spp.) and berberine derived from the Berberidaceae family. Several different studies indicate important cardiovascular effects of hawthorn and berberine. For example, both exert positive inotropic effects and have been used in the treatment of congestive heart failure. Recently, it was shown that hawthorn extract preparations cause negative chronotropic effects in a cultured neonatal murine cardiomyocyte assay independent of beta-adrenergic receptor blockade. The aim of this study was to further characterize the effect of hawthorn extract to decrease the contraction rate of cultured cardiomyocytes. We hypothesized that hawthorn extract may be acting through muscarinic receptors to decrease contraction rate of cardiomyocytes. Atrial and ventricular cardiomyocytes were treated with hawthorn extract in the presence of atropine or himbacine. Changes in the contraction rate of cultured cardiomyocytes revealed that both muscarinic antagonists significantly attenuated the negative chronotropic activity of hawthorn extract. Using quinuclidinyl benzilate, L-[benzylic-4,4'-3H] ([³H]-QNB) as a radioligand antagonist, the effect of a partially purified hawthorn extract fraction to inhibit muscarinic receptor binding was quantified. Hawthorn extract fraction 3 dose-dependently inhibited [³H]-QNB binding to mouse heart membranes. These findings suggest that muscarinic receptors may be involved in the negative chronotropic effect of hawthorn extracts in neonatal murine cardiomyocytes. Berberine exhibits variable positive and negative chronotropic effects in different species. Our first aim was to examine the effect of berberine in a cultured neonatal murine cardiomyocyte assay. Our study demonstrates that berberine has significant negative chronotropic actions on cardiomyocytes which is not an effect of beta-adrenergic receptor blockade. Pertussis toxin (PTX), a Gi/o protein inhibitor, blocked the negative chronotropic activity of berberine. Muscarinic, adenosine, opioid, and α₂ receptors are coupled through a G-protein (Gi/o) to adenylyl cyclase in an inhibitory fashion. Activation of these receptors are primarily responsible for PTX-sensitive negative chronotropic effects in heart. We hypothesized that berberine may be acting through one of these receptor type to decrease contraction rate of cardiomyocytes. For this purpose, we studied the effects of the muscarinic-receptor antagonists, atropine, himbacine, or AF- DX 116 on the negative chronotropic activity of berberine. Muscarinic antagonists completely blocked the effect of berberine on contraction rate of cardiomyocytes, whereas the bradycardic effect of berberine was not inhibited by the opioid, adenosine, or α2 receptor antagonists naloxone, CGS 15943, or phentolamine, respectively. Using [³H]QNB as a radioligand, we demonstrated that berberine bound to muscarinic receptors of adult mouse heart membranes with relatively high affinity. Furthermore, berberine dose-dependently inhibited [³H]QNB binding to muscarinic M2 receptors exogenously expressed in HEK 293 cells. Therefore, the findings of the present study suggest that berberine has muscarinic agonist effects in cultured neonatal murine cardiomyocytes, potentially explaining reported physiological effects of berberine. Cardiac hypertrophy represents the most important factor in the development of congestive heart failure. We investigated the inhibitory effect of berberine on hypertrophy of H9c2 cells. In rat heart-derived H9c2 myoblast cells treated with different hypertrophic agonists such as insulin growth factor II (IGF-II), arginine vasopressin (AVP), phenylephrine, and isoproterenol, protein content and size of cells were significantly increased compared to control group. However, the number of H9c2 cells after treatment with hypertrophic agonists did not differ significantly compared to control. The increases in area of cells and protein content induced by the hypertrophic agonists were inhibited by treatment with berberine in a concentration-dependent manner. Our findings have provided the first scientific evidence that berberine may have an inhibitory effect on hypertrophy of heart-derived cells, and provide a rationale for further studies to evaluate berberine's cardiac activity. / Graduation date: 2010