Ischemic stroke is a leading cause of disability and death around the world. Higher concentration of glutamate following ischemic stroke is a factor leading to cell death, including neural stem cell death. Up to now no effective treatments of ischemic stroke are available. Notoginsenoside R1 (Noto R1) is the main component of Panax notoginseng, which is a traditional Chinese medicine for the treatment of cardiovascular disease. Its protective effects on the neural cell were noted recently. The main purpose of this experimental study was to investigate the mechanism of Noto R1 against glutamate neurotoxicity on primary cultured mouse cortical neural stem cells in vitro, and its effects on ischemic stroke on mice brain in vivo. In the in vitro part, primary culture of neural stem cells was prepared from 12.5-day-old C57BL/6N mice embryos cortex. Neural stem cells were confirmed by nestin-staining and differentiation study afterwards. Then neural stem cells were incubated with Noto R1 and glutamate for 24 hours. Cells were fixed for TUNEL staining and caspase-3 staining. Protein was collected for western blot for Bax, Bcl-2, phos-AKT, JNK/SAPK, and phospho-p38 MAPK. Results showed that glutamate has cytotoxicity in a dose-dependent manner on neural stem cells. Noto R1 showed remarkable neuro-protective effects on neural stem cells exposed to excessive glutamate by higher viability. Noto R1 significantly reduced caspase-3 expression and TUNEL-positive cells. Furthermore, Noto R1 increased the protein expression of Bcl-2 and phospho-AKT, and reduced Bax expression. Moreover apoptosis pathway study showed phospho-p38 expression was suppressed in the Noto R1 group. In the in vivo part, Noto R1 was administrated systemically to mice of MCAo followed by reperfusion. Behavior score and viability rate were assessed before sacrifice. TTC staining was performed for evaluating infarct area, volume and edema. H&E staining was applied for histological examination. TUNEL staining, IHC staining of Nestin, AQP4 and GFAP were performed. In the first part of Noto R1 of 40 mg/kg or PBS was injected into venous at the onset of blood vessel occlusion for 2 hours, and then followed by 22 hours of reperfusion. Results were all negative. In the second part, Noto R1 was injected intra-peritoneum for 10 days prior to MCAo which lasted for 1 hour 50 minutes, then reperfusion was allowed for 22 hours. Results showed Noto R1 improved behavior score and viability rate. Meanwhile Noto R1 significantly reduced ischemic area, volume and edema percentage. Moreover TUNEL-positive cells in the affected cortex were significantly decreased. Nestin-positive cell in the striatum were significantly increased in the Noto R1 group, and immunoactivity of AQP4 and GFAP was apparently decrease with Noto R1 treatment. In conclusion, this study showed that Noto R1 protected cultured neural stem cells against glutamate neurotoxicity in vitro via p38 MAPK pathway by inhibiting Bax protein expression and enhancing protein expression of Bcl-2 and phospho-AKT. Moreover, it also demonstrated significant preventive effects against ischemic stroke with mice model in vivo. In a word Noto R1 presents a highly potential candidate preventing ischemic stroke clinically in the future. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

The projects described in this dissertation are focused on compounds derived from the marine environment. Chapter 1 gives an introduction to the study of marine natural products to treat human ailments and a thorough review on compounds from lithistid sponges that have been isolated or synthesized since 2000. Chapter 2 describes the isolation and structure elucidation of two sesquiterpene substituted benzoquinone derivatives, petrosiquinones A and B, from a deep-water marine sponge from the Family Petrosiidae. Although initially purified following activity in a (Sb(B-catenin/Tcf4 assay they were later followed using tumor cell line cytotoxicity assays. Petrosiquinone A was the more active of the two compounds with moderate cytotoxicity in the DLD-1, PANC-1, and AsPC-1 cell lines. In Chapter 3, the isolation and structure elucidation of two new marine-derived macrolides, madeirolide A and B, isolated from a deep-water lithistid sponge of the genus Leiodermatium is described. / They were isolated using numerous chromatographic techniques and the structures were elucidated on the basis of 1D and 2D NMR spectra coupled with high resolution-mass spectrometry (HR-MS) data. Madeirolide A and B inhibited the growth of the fungal pathogen Candida albicans with minimum inhibitory concentrations (MIC) of 12.5 and 25 (So(Bg/mL, respectively, but were not cytotoxic in tumor cell assays under the conditions tested. Chapter 4 describes work performed to determine the molecular target of lasonolide A using affinity chromatography. The target of lasonolide A is of interest since lasonolide A is known to kill cancer cells in vitro through a unique mechanism. / This chapter highlights the research performed to create an affinity matrix with immobilized lasonolide. A target has not been confirmed but there are a number of interesting hits that are being pursued. In Chapter 5, a liquid chromatography-mass spectrometry (LC-MS) screening method was established in order to rapidly identify the metabolites from numerous collections of Lyngbya spp. obtained from Broward and Lee County, Florida sites that may help marine ecologists assess the effects of Lyngbya spp. blooms on the environment. A link between the metabolites produced and nutrients from both the algal tissue and water column was also explored. / by Priscilla L. Winder. / Thesis (Ph.D.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

Current research in natural products has heavily focused on the identification of potent biologically active compounds, specifically for drug development. The project detailed in this thesis focuses on the extraction of compounds from marine invertebrates as well as defining the absolute configuration for a compound. Utilizing marine invertebrates, the sonications method developed in this thesis provides an alternative approach to rapidly extract compounds for primary screening. This method is viable compared to a traditional overnight extraction method, without suffering compound degredation... Previously, clathric acid was isolated from an unknown Clathria sp. This compound is a bibyblic C-21 terpenoid shown to have mild antimicrobial activity against gram positive bacteria. With only its relative configuration established, additional amounts of clathric acid were required to define the overall absolute configuration. Identifying the Clathria sp. to be Clathria compressa, through spicule analysis, additional sponge tissues were then collected off the coast of Boca Raton, Florida to isolate additional quatities of clathric acid. The absolulte configuration was determined through circular dichroism and the octant rule to establish a final configuration for clathric acid's four carbon stereocenters to be: (3S, 7S, 8R, and 12S). / by Rolando Rueda de Leâon. / Thesis (M.S.)--Florida Atlantic University, 2012. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Seaweeds of the genus Plocamium are known to produce a variety of halogenated monoterpenes. In addition to their ecological role as feeding deterrents, biological activities reported for these compounds include antibacterial, antialgal, antifungal and anticancer activities. An investigation of the non-polar extracts of the seaweed Plocamium corallorhiza resulted in the isolation of six known halogenated monoterpene compounds, 4-bromo-5-bromomethyl-1-chlorovinyl-2, 5-dichloro-methylcyclohexane (2.68), 1,4,8-tribromo-3 ,7-dichloro-3, 7-dimethyl-1,5-octadiene (2.67), 8-bromo-1 ,3,4,7-tetrachloro-3, 7-dimethyl-1,5-octadiene (2.66), 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2,7-octadiene (2.64), 4,8-dibromo-1,1,7-trichloro-3,7-dimethyl-2,5-octadiene (2.65) and 3,4 ,6,7-tetrachloro-3, 7-dimethyl-1-octene (2.63) as well as eight new compounds, including five halogenated monoterpene aldehydes. The new compounds were identified by 1D and 2D NMR spectroscopic techniques as: 8-Bromo-6,7-dichloro-3,7-dimethyl-octa-2,4-dienal (2.72), 8-Bromo-1,1,2,7-tetrachloro-3,7-dimethyl-octa-3,5-diene (2.70), 4,8-Dichloro-3,7-dimethyl-octa-2,4,6-trienal (2.74), 4-Bromo-8-chloro-3, 7-di methyl-octa-2, 6-dienal (2 76), 8-Bromo-4-chloro-3, 7-dimethyl-octa-2,4 ,6-trienaI (2.75), 4-Bromo-1,3,6,7-tetrachloro-3 ,7-dimethyl-octa-1,4-diene (2.71), 8-Bromo-1,3,4,7-tetrachloro-3,7-dimethyl-octa-1,5-diene (2.69), 4,6-Dibromo-3,7 -dimethyl-octa-2,7-dienal (2.73). All compounds were screened for antimicrobial activity, brine shrimp lethality and cytotoxicity towards oesophageal cancer cells. Compound 2.68 was toxic to brine shrimp larvae at a concentration of 50 μ/mL. It also showed promising activity towards oesophageal cancer cells with an IC₅₀, of 2 μg/mL.

Submitted in complete fulfillment for the Degree of Master of Technology: Biotechnology, Durban University of Technology, 2012. / Recently our understanding of cancer has advanced in the realization that apoptosis and the genes that control it have a profound effect on the malignant phenotype. It is now clear that some oncogenic mutations disrupt apoptosis, leading to tumor initiation, progression or metastasis. Conversely, compelling evidence indicates that other oncogenic changes promote apoptosis, thereby producing selective pressure to override apoptosis during multistage carcinogenesis. Finally, it is now well documented that most cytotoxic anti-cancer agents induce apoptosis, raising the intriguing possibility that defects in apoptotic programs contribute to treatment failure. Because the same mutations that suppress apoptosis during tumor development also reduce treatment sensitivity, apoptosis provides a conceptual framework to link cancer genetics with cancer therapy. An intense research effort is uncovering the underlying mechanisms of apoptosis, such that, in the next decade, one envisions that this information will produce new strategies to exploit apoptosis for therapeutic benefit. Plants have a long history in cancer treatment. More than 3000 species have been known for their anti-cancer potential. Over 60% of currently used anti-cancer agents are derived in one way or another from higher plants. Indeed, compounds derived from natural sources, including plants, have played, and continue to play, a dominant role in the discovery of leads for the development of conventional drugs for the treatment of most human diseases especially cancer. Thus the aim of this study was to investigate if Centella asiatica and Elytropappus rhinocerotis possess anti-cancer potential and determine the effect on the modulation of apoptosis. In South Africa C. asiatica is known anecdotally to treat various forms of cancers and E. rhinocerotis is known to treat colic and diarrhoea. The anti-cancer activity of C. asiatica has been studied in some parts India but E. rhinocerotis has not been investigated. This study was conducted using polarity guided fractionation (aqueous, ethanolic, methanolic and hexane), thereafter these extracts were tested for their toxicity on a colon cancer cell line (CaCO-2) and on normal cells vi (PBMC). Subsequently, the most active extract was used to isolate the active fraction. The fraction that displayed toxicity on the CaCO-2 cells were further investigated for their ability to induce apoptosis by observing the morphological effects and DNA changes using acridine orange-ethidium bromide staining. Apoptosis was confirmed using Annexin V- PI staining. Nuclear effects were studied by DNA fragmentation and by agarose gel electrophoresis. Nuclear fragmentation was studied by flow cytometry using bromodeoxyuridine (BrDU). Pro-apoptotic changes were determined with Caspase III enzyme levels using flow cytometry. The results were compared to the effect of a known anti-carinogen - Taxol. The anti-oxidant activity was also evaluated for the different extracts. The ethanolic extracts of both C. asiatica and E. rhinocerotis showed more than 100% radical scavenging activity. The methanolic extract (125 μg/ml -500 μg/ml) showed cytotoxicity on the CaCO-2 cells and a proliferative effect on the PBMC. Apoptosis was confirmed in the methanolic extract for both plants and was therefore used to carry forth this study. This included early apoptotic changes observed by the morphological study i.e., membrane blebbing, nuclear condensation and the presence of apoptotic bodies, in both C. asiatica and E. rhinocerotis fractions demonstrated more non-viable apoptotic cells than the methanolic extracts. Late changes of apoptosis were also found as indicated by DNA laddering and a positive outcome with BrDU. Both the active fractions from C. asiatica and E. rhinocerotis showed more DNA laddering and active caspase III than the methanolic extract. These features indicate that C. asiatica and E. rhinocerotis cause apoptotic death of colon cancer cells CaC0-2. In conclusion, there was a significant increase in apoptosis of CaCO-2 cells with little alteration of PBMC in the presence of the methanolic extract of C. asiatica and E. rhinocerotis. The semipure fractions resulted in changes related to late apoptosis. The results suggest that C. asiatica and E. rhinocerotis induces apoptosis in CaCO-2 cells which is an important step in elucidating the underlying molecular mechanism for anti-tumour activity.

Hyperuricemia is the hallmark of gout. Pathogenic mechanisms of hyperuricemia include uric acid overproduction in the liver or underexcretion in the kidney. Current antihyperuricemic agents include xanthine oxidase inhibitors in which allopurinol is the most often prescribed. Inhibitors of renal urate reabsorption such as probenecid and benzbromarone are also employed. However, these existing antihyperuricemic agents possess some undesirable effects such as hypersensitivity towards allopurinol and hepatotoxicity associated with benzbromarone. Therefore, search for alternative antihyperuricemic agents with a more favorable toxicological profile or via mechanisms other than the above two mentioned is highly warranted. / The present project represents such an effort. Four in vitro experimental models were developed for the screening of new antihyperuricemic agents. The effects of the potential compounds from natural sources on the activities of phosphoribosyl pyrophosphate synthetase, hypoxanthine-guanine phosphoribosyl transferase and xanthine oxidase, as well as the uptake of urate through rat renal brush border membrane vesicles were investigated. Several compounds emerged with strong urate uptake inhibitory activities in which morin (3, 5, 7, 2', 4'-pentahydroxyflavone) was the most potent. Interestingly some of these compounds including morin were also demonstrated to be xanthine oxidase inhibitors. The subsequent in vivo experiment showed that morin indeed exhibited hypouricemic and uricosuric actions in an acute oxonate-induced hyperuricemic rat model. The uricosuric action of morin was hirther studied in transfected HEK293 cells expressing the human urate anion transporter 1 (hURATI) which is believed to regulate blood urate level by mediating urate reabsorption. In hURAT1-expressing HEK293 cells, urate uptake was significantly increased as compared to the non-transfected parental cells. Incorporation of morin into the uptake buffer could dose-dependently inhibit urate uptake in the transfected cells. Taken together our data indicated that morin is a potentially useful antihyperuricemic agent which acts by inhibiting xanthine oxidase and inhibiting urate reabsorption. In addition, the favorable safety profile of this natural compound makes it a potential candidate worthy of further investigations. / Yu Zhifeng. / "June 2006." / Advisers: Christopher H. K. Cheng; Wing Ping Fong. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1584. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 155-169). / 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.

alpha-Glucosidase from yeast was used to screen for alpha-glucosidase inhibitory activities in Chinese herbal medicines. Seventy crude extracts were studied. The extracts of Semen Fagopyri Esculenti, Herba Euphorbiae Humifusae, Radix Polygoni Multiflori, Cortex Cinnamomi, Radix Paeoniae Rubra, and Radix Paeoniae Alba exhibited alpha-glucosidase inhibitory activities. These herbs have high potential for finding active compounds to develop into new antidiabetic drugs. / In this study, an assay technique involving brush border membrane vesicles was developed to screen for glucose uptake inhibitory actions in sixteen compounds from natural sources. Two compounds, namely naringenin and desoxyrhaponticin, were demonstrated to exhibit moderate inhibitory action on glucose uptake in rabbit intestinal brush border membrane vesicles, and showed very strong inhibitory action in rat everted intestinal sleeves. The kinetics study indicated that they behave as competitive inhibitors on glucose uptake. Moreover, they could reduce the level of the glucose uptake in the diabetic rat intestinal and renal membrane vesicles. In vivo study further demonstrated that desoxyrhaponticin could significantly reduce the glucose levels after a single oral administration of glucose in neonatal streptozotocin-induced diabetic rats, but not naringenin. These results suggest that naringenin and desoxyrhaponticin may be useful in the control of hyperglycemia. They act by inhibiting glucose uptake in the intestine and glucose reabsorption in the renal proximal tubules. / On the other hand, several synthetic compounds based on the structure of valienamine were found to show strong inhibition on intestinal alpha-glucosidases such as sucrase, glucoamylase and maltase. The strongest inhibitor was further studied. It could reduce the postprandial plasma glucose level of neonatal streptozotocin-induced diabetic rats. These results demonstrated that it has the potential to develop inter an oral antihyperglycemic agent. / The objective of this study is to improve the postprandial hyperglycemic conditions of diabetes by two approaches: (1) inhibiting the digestive enzymes (alpha-glucosidases), and (2) inhibiting active glucose transport in the small intestine. We have screened for new inhibitors of alpha-glucosidase and monosaccharide cotransporters from natural products and their derivatives. These compounds may be useful in the management of type 2 diabetes and diabetic complications. / Type 2 diabetes mellitus accounts for 90-95% of all diabetic cases and has become a major health concern over the world. There is increasing evidence that postprandial hyperglycemia, a hallmark of diabetes, plays a critical role in the development of type 2 diabetes and cardiovascular complications. Therefore the early identification of postprandial hyperglycemia and its effective control can offer the potential for early intervention and prevention of diabetic complications. / Li Jianmei. / "August 2006." / Adviser: Christopher H. K. Cheng. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1592. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 161-180). / 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.

Malaria is one of the three most deadly diseases in Africa. Although there are available treatments, their efficacy has been greatly reduced over the past two decades due to the development of resistance to currently available drugs. This has necessitated the search for new and effective antimalarial agents. This project approached the search for new antimalarial compounds in two ways: (i) by screening natural products isolated from marine algae against the Plasmodium parasite and (ii) by modification of selected isolated active compounds to target 1-deoxY-đ-xylulose 5-phosphate reductoisomerase (DXR), an enzyme found in the nonmevalonate isoprenoid biosynthetic pathway of Plasmodium Jalciparum. It was envisaged that such a compound would exhibit dual action on the Plasmodium parasite. Extracts obtained from 22 marine algae were prefractionated by solvent partitioning and were screened for anti plasmodial activity against the chloroquine sensitive (CQS) P. Jalciparum D 10 strain. Overall, 50% of the algae screened produced at least one crude fraction with activity against P. Jalciparum. Extracts of the algae Sargassum heterophyllum, Plocamium cornutum, Amphiroa ephedrea and Pterosiphonia cloiophylla gave the most promising results. Fractionation of S. heterophyllum afforded three tetraprenyltoluquinols (3.1, 3.2 and 3.5) and an all-trans-fucoxanthin (3.6). Three new compounds (4.5, 4.6 and 4.7) and two known halogenated monoterpenes (4.1 and 4.4) were isolated from P. cornutum. Each of the isolated compounds from both S. heterophyllum and P. cornutum showed antiplasmodial activity with IC₅₀ values ranging from 2.0 - 15.3 μM for S. heterophyllum and 13 - 230 μM for P. cornutum. Attempts to synthetically modify halogenated monoterpene 4.4 by dihydroxylation and phosphorylation in order to inhibit the DXR enzyme was unsuccessful. However, the hemiterpene analogue (5.42) of the halogenated monoterpenes was successfully phosphorylated and dihydroxylated to give compound 5.45 which showed promising activity against DXR. The result obtained indicated that the proposed phosphorylation and dihydroxylation of the halogenated monoterpene 4.4 would result in the synthesis of a potent DXR inhibitor and therefore a potential antimalarial agent with dual mode of action on the Plasmodium parasite.

隨著個人計算機運算能力的快速發展，虛擬藥物篩檢已被廣泛運用。目前運用於計算機輔助藥物虛擬篩選的化合物數據庫多為人工合成的數據庫，而用於天然產物藥物篩選的數據庫則較少報道。為了加速天然化合物的虛擬篩選，我們建立了包含約8000個天然產物的數據庫。他們中的大多數為傳統中藥。 / 為了驗證天然產物數據庫的可用性，其被用於篩選乙酰膽鹼酯酶抑製劑。該數據庫成功地確定了美國藥品監督管理局所批準的乙酰膽鹼酯酶抑製劑，如石杉鹼甲和他克林，表示該天然產物數據庫可以用於藥物虛擬對接篩選。 / 除了已知的乙酰膽鹼酯酶抑製劑，十二種植物化學物（大黃酸，大黃素，蘆薈大黃素，大黃酚，花椒毒素，珊瑚菜素，別異歐前胡素，歐前胡素，紫草素，乙酰紫草素，異戊紫草素和β，β-二甲基丙烯酰紫草素）被確定為新的乙酰膽鹼酯酶抑製劑。澱粉樣蛋白聚集可以導致神經細胞死亡；本研究中新發現的乙酰膽鹼酯酶抑製劑乙酰紫草素能夠阻止澱粉樣蛋白的聚集。除此之外，乙酰紫草素及其衍生物可以對抗過氧化氫誘導的神經細胞凋亡。其抗凋亡的活性作用是通過抑制活性氧的產生，以及保護線粒體膜電位的損失所實現的。亞鐵血紅素加氧酶在其神經細胞保護作用中起重要作用。 / 趨化因子受體4為跨膜G蛋白偶聯受體（GPCRs）。 CXCR4已被確定為一個新治療以及預防腫瘤轉移的新靶點。本研究利用分子對接篩選，從天然產物數據庫篩選選出CXCR4拮抗劑。通過分子對接和基於細胞的測定，黃芪甲苷，羥基紅花黃色素A和水飛薊賓已被確定為CXCR4拮抗劑。抗轉移的研究表明，黃芪甲苷和水飛薊賓抑制CXCL12誘導乳腺癌細胞的遷移和侵襲。此外，水飛薊賓也抑制CXCL12誘導的人臍靜脈內皮細胞管形成。另一方面，羥基紅花黃色素A對乳腺癌細胞的增殖表現出較強的抑製作用，因此很難進行抗轉移實驗。 / With the rapid advances in personal computing power, virtual drug screening has become increasingly popular. While there are numerous databases for synthetic compounds, there are few natural product databases that are specifically for in silico docking studies. To facilitate virtual docking on natural compounds, in-house Natural Products Database has been established, which contains approximately 8,000 naturally occurring chemicals so far. Most of them are documented Traditional Chinese Medicines. / In order to validate the usefulness of the database, in silico screening of acetylcholinesterase inhibitors (AChEIs) by virtual docking was performed. The database successfully identified the FDA-approved AChEIs such as huperzine and tacrine, indicating the in-house database is workable for natural products docking screening. / Apart from well-known AChE inhibitors, twelve phytochemicals (emodin, aloe-emodin, chrysophanol, rhein, xanthotoxin, phellopterin, alloisoimperatorin, imperatorin, shikonin, acetylshikonin, isovalerylshikonin and β, β-dimethylacrylshikonin) were identified as AChE inhibitors in this study that were not previously reported. Amyloid aggregation leads to toxic species that cause neuronal cell deaths, it was found that the newly identified AChEIs acetylshikonin and shikonin are able to prevent amyloid aggregation. A series of cell-based analysis were conducted for in vitro evaluation of the neuroprotective activities of the newly identified AChEIs. Acetylshikonin and its derivatives was found to prevent apoptotic cell death induced by hydrogen peroxide in human and rat neuronal SH-SY5Y and PC12 cells at 10 μM. Acetylshikonin exhibited the most potent anti-apoptotic activity through inhibition of reactive oxygen species (ROS) generation as well as protection of the loss of mitochondria membrane potential. Furthermore, acetylshikonin upregulates hemooxygenase 1(HO-1) which is a key step mediating its anti-apoptotic activity from oxidative stress in SH-SY5Y cells. / The C-X-C chemokine receptor type 4 (CXCR4) belongs to the class A family of seven transmembrane G protein-coupled receptors (GPCRs). CXCR4 has been identified as one of novel target against metastasis. A search for natural CXCR4 antagonists was conducted from natural product database by molecular docking for anti-metastasis study. Astragaloside IV, hydroxy safflower yellow A and silibinin have been identified as novel CXCR4 antagonists by both molecular docking and characterized by various cell-based assays. Anti-metastasis study showed that astragaloside IV and silibinin inhibited CXCL12-induced migration and invasion in breast cancer cells. In addition, silibinin also inhibited CXCL12-induced tube formation in human umbilical vein endothelial cells. On the other hand, hydroxy safflower yellow A exhibited a strong cytotoxicity on breast cancer cell proliferation, which is difficult to conduct anti-metastasis experiments. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Wang, Yan. / Thesis (Ph.D.) Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 230-250). / Abstracts also in Chinese.