Metabolic syndrome refers to clusters of risk factors (e.g. obesity, hyperlipidemia, insulin resistance, non-alcoholic fatty liver and hypertension) that would lead to development of cardiovascular disease. The prevalence of this disease is high and the therapeutic approaches are insufficient. Potential use of Chinese herbal medicines to target on metabolic syndrome has attracted great attention. Erigerontis Herba (EH) is a Chinese herb that is traditionally used to treat cardiovascular and cerebrovascular diseases. Its effect on diet-induced metabolic syndrome has not been previously investigated. The present study was the first investigation of the effects of Erigerontis Herba, Erigerontis containing herbal formulae and its polyphenol-enriched fraction (EHP) on diet-induced metabolic syndrome. / To determine the effects of EH, EH-containing herbal formulae and EHP on obesity, hyperlipidemia, hepatic steatosis and hypertension, in vitro, ex vivo and in vivo models were used. For in vitro studies, cholesterol uptake inhibition and adipogenesis differentiation assays were performed using Caco-2 cells and 3T3-L1 adipocytes, respectively. Ex vivo organ bath studies were performed to determine the vasodilative effects, and respective underlying mechanisms were determined via inhibition of different pathways using corresponding blockers. In vivo animal model of high-fat diet-induced metabolic syndrome was performed using C57Bl/6 mice. Preventive effects of these herbal extracts were determined by supplementation of extract to high-fat diet for 8 weeks, followed by measurement of body weight, liver and adipose tissues weight, plasma lipid, plasma glucose and liver lipid. Proteins and genes expressions related to lipid metabolism were also determined using Western blotting and RT-PCR. Bioavailability of these herbal extracts were investigated using human intestinal Caco-2 cells monolayer. / Among all tested, EHP demonstrated most prominent effects in the inhibition of both cholesterol uptake and adipogenesis in vitro; and possessed significant vasodilative effects ex vivo, and also significant beneficial effects on obesity and hepatic steatosis in mice, but not on hyperlipidemia. EH-containing herbal formulae exhibited significant inhibitory effects on cholesterol uptake in Caco-2 cells. Among all tested, only DZ4 showed inhibitory effect on adipogenesis. EH, on the other hand, significantly inhibited adipogenesis but exerted no effect on cholesterol uptake. EH and EH-containing herbal formulae showed significant vasodilative effects in ex vivo studies. For in vivo studies, only DZ6 showed mild beneficial effects on diet-induced obesity (inguinal fat/body weight and peri-renal fat/body weight), hepatic steatosis and hyperlipidemia. EH alone showed no significant beneficial effects on high-fat diet-induced metabolic syndrome in mice. Preliminary bioavailability experiments suggested that all herbal preparations had relatively low bioavailability, although EHP had a comparative higher permeation ability through Caco-2 monolayer. / In conclusion, this is the first comprehensive study of the effects of EH (with or without other herbs) on diet-induced metabolic syndrome. EHP, a polyphenol-enriched fraction isolated from EH showed potent beneficial effect on diet-induced obesity and hepatic steatosis both in vitro and in vivo, as well as significant vasodilative effects ex vivo. These data suggested the potential for EHP to be developed as dietary supplementation for metabolic syndrome. The effects will be further determined in clinical trials in the future. / 代謝綜合癥是多種心血管危險因子異常聚集的病理狀態，其病癥包括肥胖，高血脂，胰岛素抗性，高血糖，脂肪肝和高血壓等。它的發病率很高，但是目前治療以及預防這一疾病的措施尚不完善。近年來，用中藥治疗這一疾病引起人们廣大關注。燈盞細辛作為傳統中草藥經常用於心血管和腦血管疾病，但其對於代謝綜合癥是否有效有待研究發現。本課題組建立了高脂餵食引起代謝綜合癥模型，并探討了燈盞細辛，燈盞細辛複方，以及燈盞細辛你酚類對此疾病的療效及作用機制。 / 我們用體內，體外及離體模型研究了燈盞細辛，燈盞細辛複方以及燈盞細辛酚對於肥胖，高血脂，脂肪肝和高血壓的作用。我們用3T3-L1和Caco-2細胞模型研究了燈盞細辛相關提取物對於膽固醇吸收和脂肪生成的作用，用大鼠離體血管環體外實驗，研究了他們對於血管擴張的作用及其機制。另外，本課題組建立了高脂餵食小鼠代謝綜合癥模型，并探討了這些中藥提取物作為食物補充劑對於代謝綜合癥的作用。我們用實時定量PCR技術和蛋白質印跡技術測量了各種相關蛋白和基因的表達。此外，我們還用人的腸細胞單層轉運模型研究了這些中藥提取物的生物利用度。 / 體外實驗結果表明，四個燈盞細辛複方都有明顯抑制膽固醇吸收的作用，但是對於脂肪生成，只有複方DZ4有明顯抑制作用。燈盞細辛提取物可以明顯抑制脂肪生成，但是對膽固醇吸收卻沒有明顯作用。燈盞細辛酚對於兩者都具有明顯的抑制作用。另外，大鼠離體動血管環研究結果顯示，燈盞細辛複方，燈盞細辛提取物以及燈盞細辛酚都有明顯的擴張血管的作用。高脂餵食小鼠代謝綜合癥實驗結果結果顯示四個燈盞細辛複方中只有複方DZ6對於肥胖，脂肪肝和高血脂有作用。燈盞細辛對代謝綜合癥無明顯作用，但是燈盞細辛酚對于肥胖和脂肪肝卻有明顯抑制作用對於此代謝綜合癥小鼠模型。生物利用度相關研究結果顯示，燈盞細辛，燈盞細辛複方以及燈盞細辛酚的生物利用度都相對較低。 / 總括來說，我們綜合研究了燈盞細辛對於代謝綜合癥的藥效。燈盞細辛酚對於肥胖和脂肪肝在體內體外模型都顯示了較好的抑製作用。再加上其對於擴張血管有非常明顯的作用，它有潛能被發展為代謝綜合癥的治療預防方法。 / Wang, Yanping. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 243-256). / Abstracts also in Chinese. / Title from PDF title page (viewed on 01, November, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_1290695 |
| Date | January 2014 |
| Contributors | Wang, Yanping (author.), Fung, Kwok-pui (thesis advisor.), Leung, Ping-Chung , 1941- (thesis advisor.), Lau, Clara Bik-San (thesis advisor.), Chinese University of Hong Kong Graduate School. Division of Chinese Medicine. (degree granting institution.) |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography, text |
| Format | electronic resource, electronic resource, remote, 1 online resource (xxx, 256 leaves) : illustrations (some color), computer, online resource |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons "Attribution-NonCommercial-NoDerivatives 4.0 International" License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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