Indiana University-Purdue University Indianapolis (IUPUI) / Enhancing osteoblast proliferation, survival, and extracellular matrix protein secretion are potential therapeutic approaches to treat bone fractures and diseases such as osteoporosis. BENS is a traditional medicine used in many countries such as India for thousands of years to treat many diseases including bone diseases. In this study, molecular, cell-based and in vivo approaches were utilized to investigate the effects of BENS on bone and cartilage regeneration. An osteosarcoma cell line (MG63) was incubated in serum free media with and without 0.8 mg/ml of BENS. BENS significantly increased cell survival up to 30 days and these cells retained their ability to proliferate in fresh media with serum. After adding BENS, there were statistically significant decreases in the expression of both anti-apoptotic and pro-apoptotic proteins. An in vivo non-critical size segmental bone defect Xenopus system was used to evaluate the ability of BENS to enhance cartilage formation. After a small segment of the anterior hemisection of the tarsus bone was excised, the frogs were divided into three groups and given subcutaneous injections of either phosphate-buffered saline or BENS once daily for 30 days and then bone/cartilage formation evaluated. The total cartilage area/total section area was significantly increased (2.6 fold) in the BENS treated samples. In an osteoporotic rat model, the anabolic properties of BENS on bone mass were assessed by histomorphometric analyses. Ovariectomized (OVX) rats received daily intraperitoneal injections for 4 weeks. Bone formation rates (BFRs) for the cortical periosteal bone surface of the midshaft tibia were 383.2, 223.9, 308.8, 304.9, and 370.9 µm3/µm2/year, and for the trabecular surface were 82.2, 113, 212.1, 157, and 165 µm3/µm2/year for the sham, OVX, PTH, 3 mg/kg BENS, and 30 mg/kg BENS groups, respectively. BENS increased both trabecular and cortical BFRs. It generated better results on cortical periosteal bone surface than did PTH. Taken together, these findings suggest that BENS promotes osteoblast survival due to its effects on altering the balance between pro-apoptotic and anti-apoptotic proteins. In addition, in vivo studies revealed that BENS enhanced cartilage formation in Xenopus and BFRs in rats. Therefore, BENS may possess anabolic bone/cartilage properties.

Red seaweeds are reported to represent the largest group of algae, with more species accounted for than the combination of brown and green seaweeds. Due to the high amount of polysaccharides in red seaweeds, they are mainly utilized for commercial agar and carrageenan production in industry. However, increasing studies indicate other valuable compounds such as lipids and polyphenols could be potential utilized for multiple human needs (e.g., drug development) (1, 2). With increasing studies demonstrating the potential health benefits of seaweed components, two red seaweed species commonly consumed in Asia, hong qı´ lı´n c a`i (HQL), Eucheuma sp and zhe` gu¯ ca`i (ZGC), Caloglossa leprieurii, were investigated on to determine the anti-inflammatory effects of their extractable lipophilic bioactives (ELB) and bound lipophilic bioactives (BLB) in lipopolysaccharide( LPS)-treated RAW 264.7 macrophages. The chemical composition of ELB and BLB was characterized in terms of total phenolic content (TPC), total flavonoid content (TFC), total tannin content (TTC), oxygen radical absorbance capacity (ORAC), and etc. Six phenolic compounds were identified in ZGC extracts and one was detected in HQL. All extracts inhibited the nitric oxide (NO) production in LPS-induced macrophages, which was associated with downregulation of iNOS and COX-2 protein expression and up-regulation of HQ-1 and NQO1 protein expression. Overall, our results showed that both ELB and BLB in HQL and ZGC seaweeds presented potential anti-inflammatory activities. These results warrant future investigations to determine the mode of actions of red seaweed bioactives and their efficacy in humans.

No / Background In traditional medicine whole plants or mixtures of plants are used rather than isolated compounds. There is evidence that crude plant extracts often have greater in vitro or/and in vivo antiplasmodial activity than isolated constituents at an equivalent dose. The aim of this paper is to review positive interactions between components of whole plant extracts, which may explain this. Methods Narrative review. Results There is evidence for several different types of positive interactions between different components of medicinal plants used in the treatment of malaria. Pharmacodynamic synergy has been demonstrated between the Cinchona alkaloids and between various plant extracts traditionally combined. Pharmacokinetic interactions occur, for example between constituents of Artemisia annua tea so that its artemisinin is more rapidly absorbed than the pure drug. Some plant extracts may have an immunomodulatory effect as well as a direct antiplasmodial effect. Several extracts contain multidrug resistance inhibitors, although none of these has been tested clinically in malaria. Some plant constituents are added mainly to attenuate the side-effects of others, for example ginger to prevent nausea. Conclusions More clinical research is needed on all types of interaction between plant constituents. This could include clinical trials of combinations of pure compounds (such as artemisinin + curcumin + piperine) and of combinations of herbal remedies (such as Artemisia annua leaves + Curcuma longa root + Piper nigum seeds). The former may enhance the activity of existing pharmaceutical preparations, and the latter may improve the effectiveness of existing herbal remedies for use in remote areas where modern drugs are unavailable.

No / This study was designed to investigate the nutraceutical potential of monofloral Indian mustard bee pollen (MIMBP). MThe nutritional value of MIMBP was examined in terms of proteins, fats, carbohydrates, and energy value. Its chemical composition in terms of total polyphenol and flavonoid content was determined. MIMBP was screened for free flavonoid aglycones by developing and validating a high-performance liquid chromatography-photo diode array (HPLC-PDA) method. MIMBP was analyzed for in vitro antioxidant effect in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity. MIMBP was found to be comprised of proteins ((182.2+/-5.9) g/kg), fats ((137.7+/-6.8) g/kg) and carbohydrates ((560.6+/-17.4) g/kg), which result in its high energy value ((17 616.7+/-78.6) kJ/kg). MIMBP was found to contain polyphenols ((18 286.1+/-374.0) mg gallic acid equivalent/kg) and flavonoids ((1 223.5+/-53.1) mg quercetin equivalent/kg). The HPLC-PDA analysis revealed the presence of kaempferol ((65.4+/-0.5) mg/kg) and quercetin ((51.4+/-0.4) mg/kg) in MIMBP, which can be used as markers for determining the quality of bee pollen. The MIMBP extract showed DPPH free radical-scavenging activity with a half maximal inhibitory concentration of 54.79 mug/mL. The MIMBP was found to be a rich source of nutrients providing high caloric value, which makes it a candidate for a potential nutraceutical agent. The study also illustrated the high antioxidant content of MIMBP, especially in the principle polyphenols and flavonoids, which suggests its potential role in the prevention of free radical-implicated diseases. The DPPH-scavenging effect of MIMBP further confirmed its antioxidant potential. Additionally, we developed a simple, specific and accurate HPLC-PDA method for the identification and quantification of free flavonoid aglycones. This can be applied in future screenings of the quality of pollen collected by honeybees.

The cell cycle of eukaryotes consists of alternation between growth and DNA replication (interphase), and DNA distribution and cell-division (mitosis or M-phase). This process is regulated by a complex network of biochemical reactions. A core part of this network, called the "Cell Cycle engine" is evolutionarily conserved. The dimer of CDK1 (a protein kinase) and Cyclin proteins (the regulatory components), called M-phase Promoting Factor (MPF), and its key regulatory proteins Cdc25 and Wee1, are central parts of this cell cycle engine. Maintaining the fidelity of the DNA during the cell cycle is critical for successful propagation of the cell lineage. In the presence of unreplicated DNA, the cell cycle engine''s progress into mitosis is slowed down (or halted) by regulation of MPF activity through Cdc25 and Wee1. This regulatory event, called the unreplicated DNA checkpoint, was modeled in a rudimentary fashion in the Novak and Tyson (1993) model of frog eggs. Since then, many new experiments have uncovered relevant parts of this network. Here, we include these parts into a detailed model of the unreplicated DNA checkpoint in the cell cycle of frog-egg extracts. This work and future studies of the unreplicated DNA checkpoint will lead to its better understanding and hopefully to some strategies for tackling cancer. / Master of Science

Introdução. Uma alimentação rica em antioxidantes pode prevenir e reparar danos oxidativos causados pelas espécies reativas de nitrogênio e oxigênio, como o dano no DNA e a peroxidação lipídica e pode reduzir o risco de câncer, aterosclerose e outras doenças degenerativas. A polpa do Caryocar Brasiliense Camb, mais conhecido como pequi, é uma fruta do cerrado brasileiro que possui altos níveis de antioxidantes como os carotenóides, vitamina C e E e compostos fenólicos. Objetivos. Verificar a atividade antioxidante do óleo e do extrato da polpa do pequi na diminuição do estresse oxidativo em um modelo experimental de carcinogênese pulmonar. Métodos. O estudo foi realizado em 40 camundongos BALB/C machos: 35 animais foram submetidos a duas doses intra-peritoniais de 1,5 g/kg de uretana (U = 5), 10 destes camundongos receberam por gavagem 15uL de óleo da polpa do pequi (UO = 10), 10 animais receberam gavagem de 15uL de extrato etanólico de polpa de pequi (UE = 10) e os 10 animais restantes receberam por gavagem 3?g/kg de betacaroteno (UB = 10). 5 camundongos não receberam as doses de uretana nem a gavagem (C = 5). Após 60 dias, os grupos foram sacrificados. A defesa antioxidante enzimática foi mensurada pelo teste bioquímico. A atividade antioxidante do óleo de pequi foi avaliada nos tecidos do pulmão pelo teste bioquímico de TBARS (substâncias reativas ao ácido tiobarbitúrico) e os danos do DNA pelo método de teste de cometa. A expressão gênica e protéica das óxido nítrico sintases foi analisada por biologia molecular e imunohistoquímica, respectivamente. Resultados. O parênquima pulmonar dos animais que receberam as doses de uretana apresentaram formações neoplásicas induzidas pela carcinogênese química, em contraste com o grupo Controle. Os grupos de animais que receberam as doses de uretana e foram suplementados com o betacaroteno, o óleo e o extrato de pequi apresentaram resultados importantes na diminuição do dano no DNA, na peroxidação lipídica e na expressão protéica e gênica das isoformas da óxido nítrico sintase (NOS1, NOS2 e NOS3) ao contrário dos animais que receberam apenas as doses de uretana. Conclusão. Concluiu-se que os diferentes compostos antioxidantes encontrados no óleo e no extrato do pequi são eficientes para diminuir a expressão das enzimas óxido nítrico sintase, o dano no DNA e a peroxidação lipídica em um modelo experimental de carcinogênese pulmonar induzida pelo uretana, sugerindo que essa fruta possa contribuir no tratamento de câncer de pulmão / Introduction. A daily consumption of foods that are rich in antioxidant compounds can prevent and repair the oxidative damage caused by reactive species of oxygen and nitrogen, such as DNA damage and lipid peroxidation and can reduce the risk of cancer, atherosclerosis and other degenerative diseases. The pulp of the Caryocar brasiliense camb, most known as pequi, has high levels of antioxidant compounds such as carotenoids, phenolic compounds and vitamin C and E. Objectives. Verify the antioxidant activity of the oil and extract of the pequi pulp in diminishing of the oxidative stress in an experimental model of lung cancer. Methods. The study was performed in 40 male BALB/c mices: 35 animals were submitted to two doses of 1,5g/kg intraperitoneal of urethane (U=5), 10 of these mices received by gavage 15uL of pequi pulp oil (UO=10), 10 animals received by gavage 15uL of ethanolic extract of pequi pulp (UE=10) and the other 10 animals received by gavage 3?g/kg of betacarotene (UB=10). 5 mices didn\'t receive the urethane doses neither the gavage (C=5). After 60 days, the groups were sacrificed. The enzymatic antioxidant defense was measured by biochemical test. The antioxidant activity of pequi oil was evaluated in the lung tissues by the biochemical TBARS test (Thiobarbituric acid-reactive substances) and the DNA damage by the comet test method. Nitric oxid Synthases gene and protein expression was analyzed by molecular biology and imunohistochemestry, respectively. Results. The pulmonary parenquima of animals that received the urethane doses showed neoplasic formations induced by the chemical carcinogenesis, in contrast with the control group. The groups of animals that received the urethane doses and the treatment with the oil, extract and betacarotene showed an important result in diminishing the DNA damage, lipid peroxidation, genic and protein expression of the nitric oxid synthase isoforms (NOS1,NOS2,NOS3), different from what we found in the group that just received the urethane doses. Conclusion. The different antioxidant components in the oil and extract of the pequi pulp are efficient to diminish the oxid nitric synthase isoforms, DNA damage and lipid peroxidation in an experimental model pulmonary chemical carcinogenesis, and suggest that the consumption of the fruit can be a good alternative to contribute in the treatment of lung cancer

Introdução. Uma alimentação rica em antioxidantes pode prevenir e reparar danos oxidativos causados pelas espécies reativas de nitrogênio e oxigênio, como o dano no DNA e a peroxidação lipídica e pode reduzir o risco de câncer, aterosclerose e outras doenças degenerativas. A polpa do Caryocar Brasiliense Camb, mais conhecido como pequi, é uma fruta do cerrado brasileiro que possui altos níveis de antioxidantes como os carotenóides, vitamina C e E e compostos fenólicos. Objetivos. Verificar a atividade antioxidante do óleo e do extrato da polpa do pequi na diminuição do estresse oxidativo em um modelo experimental de carcinogênese pulmonar. Métodos. O estudo foi realizado em 40 camundongos BALB/C machos: 35 animais foram submetidos a duas doses intra-peritoniais de 1,5 g/kg de uretana (U = 5), 10 destes camundongos receberam por gavagem 15uL de óleo da polpa do pequi (UO = 10), 10 animais receberam gavagem de 15uL de extrato etanólico de polpa de pequi (UE = 10) e os 10 animais restantes receberam por gavagem 3?g/kg de betacaroteno (UB = 10). 5 camundongos não receberam as doses de uretana nem a gavagem (C = 5). Após 60 dias, os grupos foram sacrificados. A defesa antioxidante enzimática foi mensurada pelo teste bioquímico. A atividade antioxidante do óleo de pequi foi avaliada nos tecidos do pulmão pelo teste bioquímico de TBARS (substâncias reativas ao ácido tiobarbitúrico) e os danos do DNA pelo método de teste de cometa. A expressão gênica e protéica das óxido nítrico sintases foi analisada por biologia molecular e imunohistoquímica, respectivamente. Resultados. O parênquima pulmonar dos animais que receberam as doses de uretana apresentaram formações neoplásicas induzidas pela carcinogênese química, em contraste com o grupo Controle. Os grupos de animais que receberam as doses de uretana e foram suplementados com o betacaroteno, o óleo e o extrato de pequi apresentaram resultados importantes na diminuição do dano no DNA, na peroxidação lipídica e na expressão protéica e gênica das isoformas da óxido nítrico sintase (NOS1, NOS2 e NOS3) ao contrário dos animais que receberam apenas as doses de uretana. Conclusão. Concluiu-se que os diferentes compostos antioxidantes encontrados no óleo e no extrato do pequi são eficientes para diminuir a expressão das enzimas óxido nítrico sintase, o dano no DNA e a peroxidação lipídica em um modelo experimental de carcinogênese pulmonar induzida pelo uretana, sugerindo que essa fruta possa contribuir no tratamento de câncer de pulmão / Introduction. A daily consumption of foods that are rich in antioxidant compounds can prevent and repair the oxidative damage caused by reactive species of oxygen and nitrogen, such as DNA damage and lipid peroxidation and can reduce the risk of cancer, atherosclerosis and other degenerative diseases. The pulp of the Caryocar brasiliense camb, most known as pequi, has high levels of antioxidant compounds such as carotenoids, phenolic compounds and vitamin C and E. Objectives. Verify the antioxidant activity of the oil and extract of the pequi pulp in diminishing of the oxidative stress in an experimental model of lung cancer. Methods. The study was performed in 40 male BALB/c mices: 35 animals were submitted to two doses of 1,5g/kg intraperitoneal of urethane (U=5), 10 of these mices received by gavage 15uL of pequi pulp oil (UO=10), 10 animals received by gavage 15uL of ethanolic extract of pequi pulp (UE=10) and the other 10 animals received by gavage 3?g/kg of betacarotene (UB=10). 5 mices didn\'t receive the urethane doses neither the gavage (C=5). After 60 days, the groups were sacrificed. The enzymatic antioxidant defense was measured by biochemical test. The antioxidant activity of pequi oil was evaluated in the lung tissues by the biochemical TBARS test (Thiobarbituric acid-reactive substances) and the DNA damage by the comet test method. Nitric oxid Synthases gene and protein expression was analyzed by molecular biology and imunohistochemestry, respectively. Results. The pulmonary parenquima of animals that received the urethane doses showed neoplasic formations induced by the chemical carcinogenesis, in contrast with the control group. The groups of animals that received the urethane doses and the treatment with the oil, extract and betacarotene showed an important result in diminishing the DNA damage, lipid peroxidation, genic and protein expression of the nitric oxid synthase isoforms (NOS1,NOS2,NOS3), different from what we found in the group that just received the urethane doses. Conclusion. The different antioxidant components in the oil and extract of the pequi pulp are efficient to diminish the oxid nitric synthase isoforms, DNA damage and lipid peroxidation in an experimental model pulmonary chemical carcinogenesis, and suggest that the consumption of the fruit can be a good alternative to contribute in the treatment of lung cancer

Leung, Yu Tim. / Thesis submitted in: November 2006. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 103-128). / Abstracts in English and Chinese. / Thesis Committee --- p.i / Acknowledgements --- p.ii / Abstract --- p.iii / 摘要 --- p.iv / Table of Contents --- p.v / List of Tables --- p.ix / List of Figures --- p.x / Abbreviations --- p.xiii / Chapter 1. --- Introduction / Chapter 1.1 --- Flower herbal teas --- p.1 / Chapter 1.2 --- R. rugosa --- p.3 / Chapter 1.2.1 --- The phytochemistry of R. rugosa --- p.3 / Chapter 1.3 --- Secondary metabolites --- p.4 / Chapter 1.4 --- Classification of secondary metabolites --- p.6 / Chapter 1.5 --- Phenolic compounds --- p.6 / Chapter 1.5.1 --- Phenylpropanoid compounds --- p.6 / Chapter 1.5.2 --- Lignins --- p.7 / Chapter 1.5.3 --- Coumarins --- p.7 / Chapter 1.5.4 --- Stilbenes --- p.8 / Chapter 1.5.5 --- Tannins --- p.8 / Chapter 1.5.6 --- Flavonoids --- p.9 / Chapter 1.6 --- Oxidative Stress --- p.13 / Chapter 1.6.1 --- Diseases related to ROS --- p.13 / Chapter 1.6.2 --- Significant chemical or biochemical conversion of ROS --- p.14 / Chapter 1.6.3 --- Sources of ROS --- p.15 / Chapter 1.7 --- Natural dietary antioxidants --- p.15 / Chapter 1.7.1 --- Vitamin C --- p.15 / Chapter 1.7.2 --- Vitamin E --- p.16 / Chapter 1.7.3 --- Carotenoids --- p.16 / Chapter 1.7.4 --- Phenolic compounds --- p.16 / Chapter 1.8 --- Cancinogenesis --- p.17 / Chapter 1.9 --- Cell cycle --- p.18 / Chapter 1.9.1 --- Cell cycle of eukaryotic cells --- p.18 / Chapter 1.9.2 --- Checkpoints of cell cycle --- p.18 / Chapter 1.10 --- Cancer cell lines --- p.19 / Chapter 1.11 --- The growth phases of cancer cell lines --- p.20 / Chapter 1.12 --- Antiproliferative effects of phenolic compounds --- p.21 / Chapter 1.13 --- Genotoxicity of phenolic compounds --- p.22 / Chapter 1.14 --- Objectives --- p.23 / Chapter 2. --- Methods and Materials / Chapter 2.1 --- Extraction of active substances --- p.40 / Chapter 2.2 --- Determination of antioxidant activities TEAC assay --- p.40 / Chapter 2.3 --- Determination of hydroxy 1 radical scavenging activity by the deoxyribose assay --- p.41 / Chapter 2.4 --- Determination of phenolic contents by Folin´ؤCiocalteu assay --- p.43 / Chapter 2.5 --- Determination of total flavonoid by aluminum chloride colorimetric method --- p.43 / Chapter 2.6 --- Determination of oxidative DNA damage by comet assay --- p.44 / Chapter 2.7 --- Cell lines propagation --- p.49 / Chapter 2.8 --- Determination of antiproliferative activities by MTT assay (colorimetric) --- p.50 / Chapter 2.9 --- Determination of antiproliferative activities by BrdU labeling assay --- p.52 / Chapter 2.10 --- Cell cycle analysis by flow cytometry --- p.55 / Chapter 2.11 --- Determination of genotoxicity by SOS chromotest --- p.57 / Chapter 3. --- Results / Chapter 3.1 --- Dermination of antioxidant activities by TEAC assay --- p.59 / Chapter 3.1.1 --- Trolox Standard Reference --- p.59 / Chapter 3.1.2 --- TEAC of the seven flower extracts --- p.59 / Chapter 3.2 --- Hydroxyl radical scavenging activity by deoxyribose assay --- p.60 / Chapter 3.3 --- Determination of phenolic contents by Folin´ؤCiocalteu assay --- p.60 / Chapter 3.4 --- Determination of total flavonoids by colorimetirc aluminium chloride assay --- p.61 / Chapter 3.5 --- "The Inter-correlation between the antioxidant activities, total phenolic and flavonoid contents of flower extraction powders" --- p.61 / Chapter 3.6 --- Determination of oxidative DNA damage by comet assay --- p.62 / Chapter 3.7 --- Determination of antiproliferative activities by MTT assay --- p.63 / Chapter 3.7.1 --- Antiporoliferative activities on HepG2 --- p.63 / Chapter 3.7.2 --- Antiproliferative activities on MCF7 --- p.63 / Chapter 3.7.3 --- IC50 of R. rugosa extract on both HepG2 and MCF7 --- p.64 / Chapter 3.8 --- "The Inter-correlation between antioxidant activities, total phenolic contents, flavonoid contents, and the antiproliferative activities of flower extraction Powders" --- p.64 / Chapter 3.9 --- Determination of DNA synthesis by BrdU labeling analysis --- p.65 / Chapter 3.10 --- Cell cycle analysis by flow cytometry --- p.65 / Chapter 3.11 --- Determination of genotoxicity by SOS chromotest --- p.66 / Chapter 4. --- Discussions / Chapter 4.1 --- Extraction method --- p.90 / Chapter 4.2 --- Comparison of TEAC of the dry flowers with other foods --- p.90 / Chapter 4.3 --- Correlation between ABTS+ and hydroxyl scavenging ability of flower extraction powder --- p.91 / Chapter 4.4 --- Comparison of phenolic contents of the fry flowers with other foods --- p.92 / Chapter 4.5 --- Correlation between total phenolic contents and flavonoid contents of flower Eextraction powders --- p.92 / Chapter 4.6 --- "Correlation between total phenolic, flavonoid content and antioxidant activities of flower extraction powders" --- p.93 / Chapter 4.7 --- Factors affecting the antioxidant power besides total phenolic contents --- p.94 / Chapter 4.8 --- Synergistic effect of phenolic compounds --- p.94 / Chapter 4.9 --- Toxicity of drinking flower herbal tea --- p.95 / Chapter 4.10 --- Recommended dose of flower herbal teas --- p.96 / Chapter 4.11 --- Antiproliferative activities of flower extracts by MTT assay --- p.97 / Chapter 4.12 --- Antiproliferation activities of flower extraction Powders by Brdu labeling assay --- p.98 / Chapter 4.13 --- Protective effects of flower extraction powder on oxidative DNA damage determined by comet assay --- p.99 / Chapter 4.14 --- Cell cycle analysis --- p.100 / Chapter 4.15 --- Further Studies --- p.101 / Chapter 5. --- Conclusion --- p.102 / Chapter 6. --- References --- p.103

Hong, Sijia. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 197-234). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Colorectal cancer is the second leading cause of cancer-related mortality in Hong Kong and lack of selectivity has limited the success of conventional chemotherapy. Given the recent interest in the anti-cancer effects of traditional Chinese medicine (TCM), there are two approaches to studying its bioactivity: as a mixture of ingredients or as single compounds. The objective of the present study is to examine the anti-tumor effects of Angelicae Sinensis Radix (DG) and Garcinia hanburyi resin (TH) using both approaches, respectively, as they are traditionally used to treat inflammation. In the present study, their anti-cancer effects and the mechanisms of actions were examined for the development of potential novel chemotherapeutic drugs for colon cancer since inflammation is a predisposing factor for colon cancer. / DG extract and its three main bioactive phtbalides: n-butylidenephthalide, senkyunolide A and z-ligustilide (LGT), were found to be cytotoxic to HT-29 cells with IC50 values (24 h) of 20.70 +/- 0.85, 72.51 +/- 8.65, 18.74 +/- 1.14 and 41.98 +/- 3.64 mug/ml, respectively. The results evidenced that LGT induced G0/G 1 arrest and apoptosis, triggering cleavage of PARP, pro-caspases-3, -8 and -9 and nuclear fragmentation. LGT and cisplatin synergistically reduced the viability of HT-29 cells. More interestingly, DG extract was more potent than individual phthalides, suggesting that there are other bioactive components and/or synergistic interactions. / Individual compounds purified from TH were investigated because gambogic acid isolated from this herb has been used clinically to treat cancer, 30-Epicambogin (EPC) and guttiferone K (GUTK) showed the highest cytotoxic selectivity and potency on HT-29 cells among 15 isolated compounds. IC50 values (24 h) for EPC and GUTK in HT-29 cells were 5.36+/-0.25 and 5.39+/-0.22 muM, respectively, and both induced G0/G1 arrest by down-regulation of cyclins D1, D3, CDK4 and CDK6, while up-regulation of p21Waf1/CiP1 and p27KiP1. Both compounds triggered the activation of caspases-3, -8 and -9 in apoptosis. The in vivo anti-tumor effects of GUTK were further investigated by using a subcutaneous Colon-26 mouse tumor model. GUTK (10 mg/kg i.p.) reduced tumor volume by 33.6% and potentiated the anti-tumor effects of 5-fluorouracil when administered concurrently. / Our findings revealed that DG rather than individual phthalides, is worthy for further study as a potential anti-cancer drug, due to the synergistic interactions among multi-components in the herb. On the other hand, EPC and GUTK, isolated from TH have potential to be developed as novel anti-tumor candidates for combination use with 5-fluorouracil. The results strongly support the use of different approaches to study TCM for chemotherapy, according to its traditional and empirical use. / Subsequently, the anti-proliferative effects of DG and Chuanxiong Rhizoma (CX) extracts and mixtures containing three phthalides in the proportions similar to their presence in both extracts were examined, since CX also contains the same phthalides, but in different proportions. DG extract was significantly more potent than its corresponding phthalide mixture to inhibit cancer cell proliferation and synergistic interaction was observed among the phthalides and other bioactive components, while the phthalides in CX extract interacted antagonistically with other components. / Kan, Lai Ting Winnie. / Adviser: Ge Lin. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 267-311). / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.