UM E-Theses Collection (澳門大學電子學位論文庫)
Anti-angiogenic activities of flavonoids from Pericarpium Citri Reticulatae on human umbilical vein endothelial cells (HUVECs) and zebrafish
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Angiogenesis, the growth of new blood vessels from preexisting vasculature, is a physiological process involved in embryonic development, wound healing and female reproductive cycle. However, excessive angiogenesis is related to many fatal and chronic diseases including rheumatoid arthritis, psoriasis and cancers. For that reason, anti-angiogenic therapy becomes a new strategy for treatment of those diseases. Pericarpium Citri Reticulatae, named Chen Pi in Chinese, has widely been used as traditional Chinese medicine for thousands of years, to mainly strengthen spleen, treat vomit, cough and eliminate phlegm. Its related Chinese medicinal prescriptions are also commonly applied in the treatment of chronic bronchitis. We hypothesize that flavonoids in Chen Pi possesses anti-angiogenic activity which contributes to its traditional use on therapy of chronic bronchitis by suppressing inflammation. In this study, HUVEC in vitro and zebrafish in vivo models have been used to screen and identify the active ingredients in Chen Pi extract, and to address the mechanism of actions underlying the anti-angiogenic activity. Six flavonoids have been found to exert active but differential anti-angiogenic activities in HUVEC culture and zebrafish embryos. Among them, sinensetin is the iii most effective and potent anti-angiogenic compound. Moreover, sinensetin significantly suppresses the formation of angiogenic vessels in zebrafish in vivo, and inhibites HUVEC proliferation and migration in vitro. It exerted anti-angiogenesis by inducing G0/G1 phase arrest of cell-cycle in vitro and down-regulating the mRNA expression of angiogenesis-related genes, flt1, kdra and hras, in zebrafish in vivo. In short, the present study, for the first time, demonstrates the anti-angiogenic activity of sinensetin. All the results provide evidences supporting that sinensetin could be a potential therapeutic angiogenic agent for further development on the treatment and/or prevention of diseases associated with excessive angiogenesis. Key words: Pericarpium Citri Reticulatae, sinensetin, polymethoxylated flavone, anti-angiogenesis, zebrafish, HUVEC, flt1, kdra, cell-cycle
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Lam, In Kei
Institute of Chinese Medical Sciences
Medicinal plants -- China -- Analysis.
Blood-vessels -- Growth.
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