Lo, Yu Ching. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 79-82). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abbreviations --- p.ii / Abstract --- p.iii / Table of Contents --- p.v / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Basic Theory of FTIR --- p.1 / Chapter 1.1.1 --- Infrared Spectroscopy --- p.1 / Chapter 1.1.2 --- Dispersive Infrared Spectrometer --- p.2 / Chapter 1.1.3 --- Fourier Transform Infrared Spectrometer (FTIR) --- p.3 / Chapter 1.1.4 --- Advantages of FTIR --- p.5 / Chapter 1.1.4.1 --- Multiplex advantage --- p.5 / Chapter 1.1.4.2 --- Throughput advantage --- p.5 / Chapter 1.2 --- Traditional Chinese Medicine (TCM) --- p.6 / Chapter 1.3 --- Identification of Traditional Chinese Herbal Medicine --- p.8 / Chapter 1.3.1 --- Traditional method for the identification of TCM --- p.8 / Chapter 1.3.2 --- Instrumental method for the identification of TCM --- p.9 / Chapter 1.3.2.1 --- Identification of TCM using fingerprint method --- p.9 / Chapter 1.3.3 --- Identification of TCM using FTIR fingerprint method --- p.10 / Chapter 1.4 --- Objective --- p.11 / Chapter Chapter 2 --- Experimental / Chapter 2.1 --- Outline of the Method --- p.12 / Chapter 2.2 --- Reagents and Glassware --- p.13 / Chapter 2.3 --- Instrumentation --- p.13 / Chapter 2.4 --- Library Search Program --- p.13 / Chapter 2.5 --- Samples --- p.14 / Chapter 2.6 --- Sample Pretreatment --- p.16 / Chapter 2.7 --- Extraction of Ingredients --- p.16 / Chapter 2.8 --- Preparation of KBr Pellet --- p.17 / Chapter 2.9 --- IR Spectrum Measurement --- p.17 / Chapter 2.10 --- Data Processing --- p.18 / Chapter 2.11 --- IR Databases --- p.18 / Chapter 2.12 --- Reproducibility of Extraction --- p.29 / Chapter Chapter 3 --- Application of Library Search Techniques - Results and Disscussion / Chapter 3.1 --- Introduction --- p.31 / Chapter 3.2 --- Euclidean Search Method --- p.32 / Chapter 3.2.1 --- Similarly score of reference spectra --- p.32 / Chapter 3.2.2 --- Similarity score of known sample spectra --- p.37 / Chapter 3.3 --- Soft Independent Modeling of Class Analogy (SIMCA) --- p.45 / Chapter 3.3.1 --- Verification Diagnostic Report of the Reference flowers --- p.47 / Chapter 3.3.2 --- Classification of Flowers --- p.51 / Chapter 3.4 --- Performance Limitation --- p.75 / Chapter 3.4.1 --- Euclidean Search Method --- p.75 / Chapter 3.4.2 --- SIMCA --- p.75 / Chapter 3.5 --- Conclusion --- p.77 / References --- p.79

Bioactivity-guided isolation of SFE oil led to the identification of another sesquiterpene lactone, 6-O-angeloylprenolin, containing the bioactive alpha, beta-unsaturated cyclopentenone. MTT results showed that CNE cells were more susceptible to 6-O-angeloylenolin than the normal Hs68 cells. Besides, the inhibitory effect of 6-O -angeloylenolin on the CNE cells was slightly stronger than that of cisplatin, the positive control, albeit statistical insignificance. / Both volatile oils prepared by supercritical fluid extraction (SFE) and steam distillation (SD) were evaluated for their anti-NPC potential. Results showed that SFE oil was much stronger than that of SD oil. SFE oil significantly inhibited the growth of CNE cells by dysfunctioning the mitochondria and activating caspases. Gas chromatography-mass spectrometry analysis revealed that the responsible principals in the SFE oil were likely homologues of sesquiterpene lactones. / Centipeda minima (L.) A. Br. (Compositae), a Chinese medicinal herb, is used to treat nasopharyngeal carcinoma (NPC) in the Chinese folk. However, there is a paucity of information on its anticancer activities. In particular, both of its anti-NPC potential and the potent constituents remain elusive. / In this study, the n-hexane fraction of C. minima showed broad spectrum of inhibitory effects on five human cancer cell lines, including the breast carcinoma MCF7 cells, the prostate carcinoma PC-3 cells, the hepatocellular carcinoma Hep G2 cells, the nasopharyngeal cancer CNE cells and the acute promyelocytic leukemia HL-60 cells, with IC 50 values ranging from 6.1 to 47.3 mug/mL. Bioactivity-guided separation of the n-hexane fraction using the CNE cells as the cellular system led to the isolation of a sesquiterpene lactone, 2beta-(isobutyryloxy)florilenalin (IF), which contained the bioactive alpha-methylene-gamma-lactone ring. IF significantly induced CNE cell death with an IC50 value of 3.1 mug/mL. Despite this potency, its effect on the normal Hs68 cells was much weaker, with an IC50 value larger than 50 mug/mL. Its inhibitory effect on the CNE cells ascribed to apoptotic induction as evidenced by the cumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation, caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage. Mechanistic study showed that both extrinsic and intrinsic apoptotic pathways were activated. In the extrinsic pathway, IF activated caspase-8, which further induced the activation of caspase-3 and caspase-7. In the intrinsic pathway, IF regulated the expressions of Bcl-2 family proteins, followed by depletion of mitochondrial membrane potential (Delta&PSgr;m), the release of cytochrome c to cytosol, the activation of caspase-9 and other downstream caspases, and finally the induction of apoptosis. / Mechanistic investigation showed that 6-O-angeloylenolin caused cell cycle arrest at S and G2/M phases and induced apoptosis in CNE cells. For the cell cycle arrest, a sharp decrease was found in the expressions of cyclin D1, cyclin D3, cdc25c, and p-cdc25c, with concomitant decrease in CDK4, cyclin A, cyclin E, p-Rb(Ser780), p21Waf1/Cip1, cdc2 and p-cdc2. For the induction of apoptosis, externalization of phosphatidylserine and depletion of Delta&PSgr;m prior to the detection of sub-G1 peak were found. Other apoptotic features including the presence of apoptotic bodies, the activation of caspase-3 activity and the cleavage of PARP were observed. Activation of caspase-8 and caspase-10 was detected. Besides, 6-O -angeloylenolin induced the release of cytochrome c and AIF to cytosol. The former formed apoptosome with caspase-9, further activated the downstream caspase-3 and caspase-7 and cleaved PARP, while the latter was translocated into the nucleus and caused large-scale DNA fragmentation. Failure of the pan-caspase inhibitor, z-VAD-fmk, to interrupt the apoptotic induction by 6-O-angeloylenolin suggested that caspase-independent pathway was involved. 6-O-Angeloylenolin was able to activate Akt, ERK and JNK pathways. But only with the addition of JNK inhibitor (SP600125), significant suppression of the 6-O-angeloylenolin-induced apoptosis was observed, suggesting the involvement of the JNK pathway in the apoptotic pathway. Taken together, this study provided a better mechanistic insight into the potential application of 6-O-angeloylenolin as a candidate for NPC treatment. / Overall, this study revealed that two sesquiterpene lactones, including IF and 6-O-angeloylenolin were found to be responsible for the potent anti-NPC effect of C. minima. This study reiterates the notion that Chinese medicinal herbs traditionally applied to cancer treatment may be good sources of anticancer drug discovery, and sesquiterpene lactone may be a group of noteworthy lead compounds displaying anti-NPC potential. / Su, Miaoxian. / Adviser: Hau Yin Chung. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 100-113). / 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.

Human viral infections are important health problem worldwide. Although much effort has been made, antiviral drugs, because of the unique properties of viruses, are relatively fewer in number and possess relatively narrow spectrum of activities as compared with antibiotics. Moreover, efficacy, drug resistance and side effect are the problems of antiviral drugs in clinical uses. Thus, it is necessary to develop new, effective and safe antiviral drug. / Thirty-seven medicinal herbs, which were collected from Guangdong province or the Hong Kong region, were selected to screen for their antiviral activities against HSV-1 and/or RSV in vitro using a cytopathic effect (CPE) reduction assay. The selection of the herbs was mainly based on their traditional use in the treatment of human infectious diseases of the skin and respiratory tract. / Three of 37 medicinal herbs, Agrimonia pilosa, Pithecellobium clypearia, and Punica granatum, showed anti-HSV-1 activity, which was possibly contributed from polyphenolic compounds in the herbal extracts. Six of 21 medicinal herbs, Blumea laciniata, Elephantopus scaber, Laggera pterodonta, Mussaenda pubescens, Schefflera heptaphylla, and Scutellaria indica, exhibited potent anti-RSV activity with 50% inhibition concentrations (IC50) ranging from 12.5 to 32 mug/ml, and the selective indices (SI) ranging from 11.2 to 40. Moreover, the anti-RSV SI values of Laggera pterodonta and Schefflera heptaphylla were found to be higher than that of ribavirin. Finally, Schefflera heptaphylla having the highest anti-RSV SI value among the active herbs was subjected to further study its antiviral activity. (Abstract shortened by UMI.) / Traditional herbal medicines have been used for a long time in the treatment of human infectious diseases in many countries, including China. Antiviral screening has shown that quite a few medicinal herbs distributed in various regions of the world possess significant antiviral activities with no or limited adverse effects, and many naturally occurring compounds exhibit antiviral activity in vitro and/or in vivo. In the present study, our objectives are to (1) screen for potential antiviral agents from selected herbal medicines traditionally used in southern China, (2) isolate and characterize the antiviral constituents from the most active herb, and (3) probe possible antiviral modes of action of the active compounds. The viruses used in the present study included respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), influenza A virus (Flu A), and coxsackie B3 virus (Cox B3). However, the present study mainly focused on searching for anti-RSV and anti-HSV-1 agents from selected Chinese herbal medicines. / Li Yaolan. / "October 2004." / Source: Dissertation Abstracts International, Volume: 66-07, Section: B, page: 3506. / Supervisors: Vincent V. E. C. Ooi; Paul P. H. But. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 160-178). / 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.

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Thesis submitted to the Faculty of Science under the school of Molecular and Cell Biology, University of the Witwatersrand, in partial fulfilment of the requirements for PhD. Gauteng, Johannesburg, 2015 / Cancer is an enormous burden of disease, accounting for millions of deaths annually worldwide. Today, more people are dying from cancer than HIV/AIDS, malaria and tuberculosis combined. According to the American Cancer Society, it is expected that the global cancer burden will double by 2030 if preventative measures are not applied. Breast and gynaecological cancers remains a big scourge in developing countries, with breast cancer being the most common cancer and gynaecological cancers accounting for approximately 25% of all cancers in women in developing countries. Currently, the standard cancer treatments include surgery, radiation and chemotherapy. Adverse toxicities have been associated with these therapies and their effectiveness is also limited to drug resistance. The cost of treatment is another major burden. Limitations associated with these conventional cancer treatments have made discoveries of novel therapeutics which exhibit less toxicity and at a lowered cost of paramount importance. Medicinal plant extracts have recently attracted attention to modern medical science research with their non-lethal activity. Currently, up to 50% of the world drugs including chemotherapeutic drugs such as taxol and camptothecin are made from natural products or their derivatives. In this study we aimed to investigate the anti-cancer properties of the medicinal plant Euphorbia tirucalli. The crude extracts of E. tirucalli extracted using butanol; hexane and methanol solvents were screened for antiproliferative activity in breast (MCF-7 and MDA-MB231), ovarian (RMG-1) and cervical (SiHa) cancer cell lines. MTT assay and Real-Time Cell Analyzer (RTCA), xCELLigence were used to determine cytotoxicity of the extracts and calculate IC50. From MTT and xCELLigence results, we observed that E. tirucalli extracts exhibited dose-dependent inhibition of cell proliferation with RMG-1 and MCF-7 cells being more sensitive than MDA-MB231 and SiHa cells to all three extracts for an unclear reason. The butanol extract appeared to exhibit iv the most cytotoxicity with all cell lines reaching IC50 at low extract concentrations. Most therapies in anticancer treatment, such as chemotherapy, mainly induce cell death by causing either G0/G1 or G2/M cell cycle arrest and then inducing an apoptotic pathway. Therefore, cell cycle arrest and the induction of apoptosis in cancer cells become the major indicators of anticancer effects. Cells were stained with propidium iodide dye to determine if cells were arrested at G0/G1 or G2/M cell cycle stages while annexin V and PI staining were used to determine the type of cell death induced by the extracts. Cell cycle analyses revealed MCF-7, MDA-MB231 and SiHa cancer cells underwent arrest at G0/G1 following treatment with the plant extracts. Annexin V and PI staining revealed different proportions of apoptotic and necrotic populations. The extracts mainly induced apoptosis on MCF-7 and MDA-MB 231 cells, with the butanolic extracts inducing the most apoptosis. RMG-1 and SiHa cells had a high proportion of cells undergoing both late apoptosis and necrosis. The molecular mechanism of cell death induction was investigated using real time PCR and western blot. From the gene expression studies, p21 was observed to be over expressed in all cells following all treatments, in line with the observed cell cycle arrest at G0/G1. The extrinsic pathway of apoptosis was identified as the type of cell death induced with caspase 8 being overexpressed in MDA-MB 231 cells treated with butanol and hexane extracts. Upon further fractionation, flavonoids and especially isorhamnetin were identified as the active compounds in these extracts. Overall, the plant contains compounds that have some activity against cell proliferation and can be a promising tool to treat cancer cells. However, more work needs to be done to verify which compounds are mainly involved.

The use of complementary and alternative medicines and therapies (CAM) in Australia and across the world is becoming increasingly prevalent. The most recent survey conducted by MacLennon et al. in 2004 [2] identified that more than half the general Australian population had used some form of CAM in the previous 12 months before the survey was conducted.[2-4] Up until now, the prevalence of CAM use among elite Australian athletes was unknown. As athletes are constantly looking to gain an advantage over their competitors through physical or psychological interventions or through the application of new technologies, it was hypothesised that the use of CAM in this group would be higher in athletes than in the general population. After surveying 497 elite Australian athletes we found that 93% of this specific population utilised at least one CAM within their lifetime. The 10 CAM (as defined by the Therapeutics Goods Administration) used most frequently were sports drinks, massage, sports bars, cereal bars, multivitamins, aloe vera, sports gels, Pilates, caffeine and yoga. There were no significant differences identified between specific sporting groups- football codes, court sports, field sports, water sports and others, with all groups reporting high usage. Sports physicians, family, coaches and friends were identified as the main sources for product information, with health food shops, sports dieticians and sports physicians being the predominant providers of the actual product. Four CAM sold on the Australian market which purported to decrease the symptoms of delayed onset muscle soreness (DOMS), or reported anti-inflammatory properties which could impact of the inflammatory response associated with DOMS were studied. Lyprinol® (an anti-inflammatory agent), topical Arnica (for symptomatic relief of soft tissue trauma), Tienchi Ginseng (proposed to relieve symptoms of DOMS) and Devil’s Claw (an analgesic and anti-inflammatory agent) were the chosen CAM. Four separate randomised, double blind placebo controlled studies comprising of 20 subjects per study were carried out with the same DOMS inducing methodology (downhill treadmill running) employed. All subjects in each of the four studies had their performance (counter movement and squat jump, maximal force), pain (visual analogue scale and muscle tenderness) and blood parameters (high sensitivity C-reactive protein, interleukin-1A, interleukin-6, tumour necrosis factor-K, creatine kinase and myoglobin) analysed seven times over five days. Lyprinol® did not affect performance, pain or blood markers of muscle damage and inflammation analysed in this study. Despite Lyprinol® being marketed as having “potent anti-inflammatory” properties, Lyprinol® did not demonstrate any antiinflammatory properties in our sample group at a dose of 200mg daily for two months, and did not alter any of the markers of inflammation after a downhill running protocol. A significant difference was identified in quadriceps muscle tenderness between the topical Arnica and placebo groups 72 hours after the downhill running protocol. This indicated that the topical Arnica group experienced less quadriceps pain at this time point, though this was not reflected in the quadriceps visual analogue scale results. There were significant differences identified between the topical Arnica and placebo groups for muscle tenderness in the gastrocnemius and tumour necrosis factor-K concentration at baseline. Further statistical analysis assessing relative changes from baseline did not demonstrate any statistically significant differences between the groups for either of these parameters. We therefore conclude that the symptomatic relief of soft tissue trauma claimed from a topical Arnica product sold in Australia was not conclusively demonstrated in this study. The single, isolated significant difference identified in quadriceps tenderness does not conclusively, from this study, indicate efficacy for the use of this topical Arnica for the relief of soft tissue trauma. Tienchi Ginseng demonstrated the most promising outcomes, with statistically significant differences identified in performance and inflammatory markers in favour of Tienchi Ginseng. Though it cannot be conclusively deemed beneficial for DOMS from this study alone, Tienchi Ginseng warrants further research with larger sample sizes and a similar muscle damage protocol. Finally, Devil’s Claw did not demonstrate beneficial outcomes in regards to DOMS within this study. It actually demonstrated some, perhaps detrimental effects, upon analysis of performance and inflammatory markers. We are unsure of the mechanisms behind these findings, particularly when considering the proposed anti-inflammatory effects of Devil’s Claw. From the literature, Devil’s Claw appears to be beneficial in chronic musculoskeletal conditions however it does not seem to impact on muscle damage and pain resulting from DOMS inducing exercise. The questionnaire study has demonstrated that there is a high usage of CAM among elite Australian athletes, an area up until now that has been unexplored. The onset of CAM use within the Australian athletic population, and the prevalence of CAM use by other professional Australian athletes would be an area to explore in the future. In regards to products which specifically claim to benefit athletes suffering soft tissue trauma such as DOMS, convincing evidence for specific product use was not demonstrated in these studies. Further research involving greater sample sizes may reveal more definitive outcomes, specifically in regards to the use of Tienchi Ginseng. / Doctor of Philosophy (PhD)

Although Hormone Therapy (HT) is the most effective treatment for alleviating menopausal vasomotor symptoms and reducing bone loss, many women are reluctant to take this treatment due to side effects and concerns about safety. Epidemiological studies suggest that a significant proportion of women use Complementary and Alternative Medicine (CAM) therapies to alleviate vasomotor symptoms and improve quality of life. Anecdotal and clinical evidence indicate a number of CAM therapies, such as herbal medicine, may be effective in alleviating symptoms and modulating bone metabolism. Hence, in the context of concerns over the safety of HT and the extensive history of the clinical use of herbal medicine, this thesis investigated issues pertinent to CAM use and the menopausal transition. The aims of this thesis were to: • Examine the nature and extent of CAM use by women transitioning through menopause • Evaluate the effectiveness of a herbal formula containing Chinese herbs and Cimicifuga racemosa for alleviating vasomotor symptoms, improving quality of life and modulating bone turnover markers. From July 2003 until July 2004 the Women’s Health during Midlife Survey recruited 1,296 women aged 45-65 who were symptomatic when transitioning through menopause or asymptomatic but taking menopause specific treatments. A validated 19-item survey instrument assessed the use of CAM modalities and menopause specific products. The instrument was completed voluntarily and anonymously by women recruited from three strata; menopause clinics, clinics of general practice and government agencies. Approximately 54% of respondents had visited a CAM practitioner and/or used a CAM product during the previous 12 months. The most popular practitioners were the naturopath (7.2%) and acupuncturist (4.8%), while soy (25.4%) and evening primrose oil (EPO, 18.4%) were the most popular products. Massage and chiropractic were considered the most effective therapies, while phytoestrogen tablets and EPO were the most efficacious products. Although 26.4% of respondents indicated their doctor asked about CAM use, 71% of CAM users said they informed their physician about using CAM. Of the 60% of women using pharmaceutical medicines, 62.5% reported using a CAM product during the preceding 12 months. The survey results confirm the continued popularity of CAM use amongst women transitioning through menopause. A number of treatments were perceived to be effective in relieving symptoms. However, communication between medical practitioners and patients about CAM use is inadequate, and given the high use of pharmaceutical medicines this oversight may unnecessarily expose women to drugherb interactions. A randomised, double-blind, placebo controlled clinical trial was conducted to evaluate the effectiveness of a herbal formula derived from two traditional Chinese herbal formulae with the addition of Cimicifuga in alleviating vasomotor symptoms. The trial recruited 93 healthy women who reported at least six vasomotor symptoms per day. After a four week baseline period, women were randomly allocated to receive either herbal treatment or identical looking placebo tablets for 16 weeks. During the trial women recorded the number and severity of their flushes on a Daily Flush Diary, and at each monthly consultation two quality of life scales were completed. Forty nine eligible trial women were entered into a pilot study to assess the effect of the formula on bone turnover markers; bone specific alkaline phosphatase and deoxypyridinoline (corrected for creatinine). The herbal formula was found to be no more effective than placebo in reducing the frequency of flushing and the composite hot flush score or in improving quality of life. The pilot study found the formula had no effect on bone turnover markers after 16 weeks of treatment. Therefore, this formula cannot be recommended as a treatment for vasomotor symptoms and is unlikely to have any long term effect on bone. The use of CAM during the menopausal transition is very popular. Although this thesis found the current herbal formula to be an ineffective treatment, the scientific evaluation of potential CAM therapies is imperative so that health care professionals and consumers can make informed decisions concerning treatment options for the alleviation of symptoms. / Doctor of Philosophy (PhD)

Thesis (M.S.) in Food Science and Human Nutrition--University of Maine, 2002. / Includes vita. Bibliography: leaves 43-48.