Atherosclerosis is the chief cause of acute coronary syndromes and may progress for many years before any noticeable clinical syndromes occur. Hyperlipidemia is the common clinical problem for people adopting a western style of living and it can initiate a series of vascular events that result in atherosclerosis. The pathological processes include the accumulation of modified lipid, mainly oxidized low-density lipoprotein (oxLDL), endothelial cell dysfunction and activation, increase in expression of adhesion molecules, activation and recruitment of inflammatory cells and induction of proliferation and migration of vascular smooth muscle cells. / Endothelial-monocyte adhesion is crucial process for the recruitment of monocyte into intima. DG (7:3), Danshen and SAB were found to inhibit TNF-alpha-induced endothelial-monocyte adhesion. They also showed inhibition on TNF-alpha induced production of chemokines, MCP-1 which promotes the transmigration of monocyte. However, it did not inhibit the production of cytokine, IL-6 which stimulates the expression of adhesion molecules such as VCAM-1 and ICAM-1. / For the in vivo study, DG (7:3) exhibited no anti-hyperlipidemic or hypolipidemic effect against diet-induced hyperlipidemia, nor did it lower cholesterol level in hamsters. Also, it did not inhibit HMG-CoA reductase activity or increase the total fecal sterols excretion. However, DG (7:3) exhibited hypocholesterolemic effect on diet-induced hyperlipidemia in the rabbit model, wherein it could lower plasma total cholesterol and liver cholesterol level. Moreover, it could significantly decrease the atheroma formation. / In the present study, the anti-oxidative effects of herbal extract/compound were measured by three in vitro assays, namely the inhibition of 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH)-induced red blood cells hemolysis, AAPH-induced cardiomyocyte (H9c2) cells death and Cu2+-induced low-density lipoprotein oxidation. The results showed that the aqueous extract of the compound formula Danshen (D) and Gegen (G) (7:3), abbreviated as DG (7:3), and an aqueous extract of Danshen as well as salvianolic acid B (SAB) exhibited anti-oxidant effect, but Gegen did not produce such effect. It was found that SAB showed a stronger anti-oxidant effect than that of ascorbic acid. / Proliferation and migration of vascular smooth muscle cells (vSMCs) are important pathological processes involved in the development of atherosclerosis. DG (7:3), Danshen and SAB were found to inhibit PDGF-induced vSMCs proliferation through G1/S cell cycle arrest. Cyclin D, a main component that governs the transition of G1 phase to S phase, was found to be down-regulated by DG (7:3), Danshen and SAB, as assessed by measurements of both protein and mRNA levels. Moreover, DG (7:3), Danshen and SAB showed anti-migratory effect against platelet-derived growth factor-induced vSMCs migration. / To summarize, DG (7:3) was found to have potential to produce anti-atherosclerotic effect by inhibiting the LDL oxidation, proliferation and migration of vascular SMC, thereby preventing the formation of atheroma plaque. / Koon Chi Man. / "March 2006." / Adviser: Kwok Pui Fung. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6324. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 246-264). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_343715 |
| Date | January 2006 |
| Contributors | Koon, Chi Man., Chinese University of Hong Kong Graduate School. Division of Biochemistry. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xxviii, 264 p. : ill.) |
| 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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