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Molecular authentication and phylogenetic studies of Chinese herbs.January 2009 (has links)
Wang, Yanli. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 90-104). / In English with some Chinese characters; abstract also in Chinese. / Acknowledgement --- p.I / Abstract --- p.III / 摘要 --- p.V / Table of Content --- p.VII / List of Figures --- p.XIII / List of Tables --- p.XV / Abbreviations --- p.XVI / Chapter Chapter 1. --- Introduction --- p.1 / Chapter 1.1. --- Traditional Chinese Medicine (TCM) --- p.1 / Chapter 1.2. --- The development history and present situation of Traditional Chinese Medicine --- p.2 / Chapter 1.3. --- Modernization of Traditional Chinese Medicine --- p.3 / Chapter 1.4. --- Authentication of Traditional Chinese Medicines --- p.4 / Chapter 1.5. --- Methods for authentication of Traditional Chinese Medicine --- p.5 / Chapter 1.5.1. --- Morphological and histological methods --- p.5 / Chapter 1.5.2. --- Chemical methods --- p.6 / Chapter 1.5.3. --- Molecular methods --- p.6 / Chapter 1.6. --- DNA regions suitable for molecular authentication of Traditional Chinese Medicine --- p.8 / Chapter 1.6.1. --- The chloroplast genome --- p.8 / Chapter 1.6.2. --- Nuclear sequences --- p.9 / Chapter 1.6.3. --- Mitochondrial genome --- p.12 / Chapter 1.7. --- Herb Tu Si Zi --- p.12 / Chapter 1.7.1. --- The identity of Traditional Chinese Medicine Tu Si Zi --- p.12 / Chapter 1.7.2. --- The medicinal values of Tu Si Zi --- p.13 / Chapter 1.7.3. --- Local substitutes of Tu Si Zi --- p.14 / Chapter 1.7.4. --- The need for molecular authentication of Tu Si Zi --- p.15 / Chapter 1.8. --- Traditional Chinese Medicinal herbs from Isodon --- p.15 / Chapter 1.8.1. --- The genus Isodon --- p.15 / Chapter 1.8.2. --- Xi Huang Cao --- p.16 / Chapter 1.8.2.1. --- Identity of Xi Huang Cao --- p.16 / Chapter 1.8.2.2. --- Medicinal values of Xi Huang Cao --- p.17 / Chapter 1.8.2.3. --- Confusions of herb Xi Huang Cao --- p.17 / Chapter 1.8.3. --- Dong Ling Cao --- p.18 / Chapter 1.8.3.1. --- Identity of Dong Ling Cao --- p.18 / Chapter 1.8.3.2. --- Medicinal values of Dong Ling Cao --- p.18 / Chapter 1.8.4. --- The molecular authentication of two Isodon herbs --- p.19 / Chapter 1.9. --- Fagaropsis and Luvunga --- p.20 / Chapter 1.9.1. --- The classification of Rutaceae --- p.20 / Chapter 1.9.2. --- Controversial taxonomic issues with Fagaropsis and Luvunga --- p.21 / Chapter 1.9.3. --- The need of phylogenetic studies of genus Fagaropsis and Luvunga --- p.23 / Chapter Chapter 2. --- Objectives --- p.24 / Chapter Chapter 3. --- Materials and Methods --- p.25 / Chapter 3.1. --- Samples used in this study --- p.25 / Chapter 3.1.1. --- Tu Si Zi (Dodder seeds) --- p.25 / Chapter 3.1.2. --- Isodon herbs --- p.28 / Chapter 3.1.3. --- Fagaropsis and Luvunga --- p.31 / Chapter 3.2. --- Methods --- p.34 / Chapter 3.2.1. --- Sample preparation --- p.34 / Chapter 3.2.2. --- Total DNA extraction --- p.34 / Chapter 3.2.2.1. --- Cetyltriethylammonium bromide extraction --- p.34 / Chapter 3.2.2.2. --- Commercial kit extraction --- p.36 / Chapter 3.2.3. --- DNA amplification --- p.38 / Chapter 3.2.3.1. --- psbA-trnH intergenic spacer --- p.39 / Chapter 3.2.3.2. --- trnL-trnF region --- p.39 / Chapter 3.2.3.3. --- ITS region --- p.42 / Chapter 3.2.4. --- Agarose gel electrophoresis --- p.43 / Chapter 3.2.5. --- Purification of PCR product --- p.44 / Chapter 3.2.6. --- Cloning --- p.46 / Chapter 3.2.6.1. --- Ligation --- p.46 / Chapter 3.2.6.2. --- Transformation --- p.46 / Chapter 3.2.6.3. --- Cell cultivation --- p.47 / Chapter 3.2.6.4. --- Plasmid extraction --- p.47 / Chapter 3.2.6.5. --- Insert confirmation --- p.49 / Chapter 3.2.7. --- DNA sequencing --- p.49 / Chapter 3.2.7.1. --- Cycle sequencing --- p.49 / Chapter 3.2.7.2. --- Purification of cycle sequencing product --- p.50 / Chapter 3.2.7.3. --- DNA analysis --- p.50 / Chapter 3.2.8. --- Sequence analysis and phylogeny construction --- p.51 / Chapter Chapter 4. --- Tu Si Zi (Dodder Seeds) - Results and Discussion --- p.52 / Chapter 4.1. --- Results --- p.52 / Chapter 4.1.1. --- Dendrogram constructed using psbA-trnH intergenic spacer --- p.52 / Chapter 4.1.2. --- Dendrogram constructed using trnL-trnF region --- p.53 / Chapter 4.1.3. --- Dendrogram constructed with the combination of psbA-trnH and trnL-trnF region --- p.59 / Chapter 4.2 --- Discussion --- p.60 / Chapter 4.2.1. --- Identification of DNA markers for Cuscuta species --- p.60 / Chapter 4.2.2. --- Molecular authentication of dodder seeds --- p.60 / Chapter Chapter 5. --- Isodon herbs - Results and Discussion --- p.64 / Chapter 5.1. --- Results --- p.64 / Chapter 5.1.1. --- Dendrogram constructed with internal transcribed spacer 1 --- p.64 / Chapter 5.1.2. --- Dendrogram established with internal transcribed spacer 2 --- p.65 / Chapter 5.1.3. --- Dendrogram established with the whole internal transcribed spacer region --- p.66 / Chapter 5.2. --- Discussion --- p.73 / Chapter 5.2.1. --- ITS region performing as DNA marker for Dong Ling Cao --- p.73 / Chapter 5.2.2. --- The identify of TCM materials of Xi Huang Cao --- p.73 / Chapter Chapter 6. --- Fagaropsis and Luvunga - Results and Discussion --- p.75 / Chapter 6.1. --- Results --- p.75 / Chapter 6.1.1. --- Phylogenetic tree constructed with internal transcribed spacer 1 --- p.76 / Chapter 6.1.2. --- Phylogenetic tree constructed with trnL-trnF region --- p.76 / Chapter 6.1.3. --- Phylogenetic tree constructed with combined of trnL-trnF region and ITS-1 region --- p.77 / Chapter 6.1.4. --- The location of Fagaropsis and Luvunga in 3 different phylogenetic trees --- p.78 / Chapter 6.2. --- Discussion --- p.85 / Chapter 6.2.1. --- Fagaropsis 一 a member of the ´بProto-Rutaceae´ة group --- p.85 / Chapter 6.2.2. --- Luvunga 一 a member of Aurantioideae --- p.86 / Chapter 6.2.3. --- DNA sequencing providing a useful methodology in plant phylogenetic studies --- p.87 / Chapter Chapter 7. --- Conclusions --- p.89 / References --- p.90 / Appendix 1. Sequence alignment ofpsbA-trnH intergenic spacer of dodder --- p.105 / Appendix 2. Sequence alignment of trnL-trnF region of dodder samples --- p.108 / Appendix 3. Sequence alignment of ITS region of Isodon herbs and specimens --- p.117 / Appendix 4. Sequence alignment of ITS-1 region of Rutaceae species --- p.124 / Appendix 5. Sequence alignment of trnL-trnF region of Rutaceae species --- p.129
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Effects of a chinese herbal medicine formula (SD) on a Drosophila sleep model.January 2008 (has links)
Yu, Siu Lung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 117-124). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / Chinese Abstract --- p.iv / Table of Contents --- p.v / List of Figures --- p.viii / List of Tables --- p.x / List of Abbreviations --- p.xi / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- General introduction of sleep --- p.1 / Chapter 1.1.1 --- Sleep disorders --- p.1 / Chapter 1.1.2 --- Classification systems for sleep disorders --- p.2 / Chapter 1.2 --- Insomnia --- p.4 / Chapter 1.2.1 --- Definition --- p.4 / Chapter 1.2.2 --- Consequences of insomnia --- p.6 / Chapter 1.2.3 --- Prevalence --- p.8 / Chapter 1.2.4 --- Subtypes of insomnia --- p.9 / Chapter 1.2.5 --- Causes --- p.12 / Chapter 1.2.6 --- Treatment of insomnia --- p.13 / Chapter 1.2.6.1 --- Cognitive-behavioral therapy for insomnia --- p.14 / Chapter 1.2.6.2 --- Pharmacological treatment for insomnia --- p.17 / Chapter 1.3 --- Traditional Chinese medicine and herbs in SD formula --- p.22 / Chapter 1.4 --- Drosophila model for studying sleep --- p.25 / Chapter 1.4.1 --- Drosophila as a disease model --- p.25 / Chapter 1.4.2 --- Drosophila Sleep --- p.26 / Chapter 1.4.3 --- Similarity of Drosophila and mammalian sleep --- p.26 / Chapter 1.4.4 --- Methods for measuring Drosophila sleep --- p.29 / Chapter 1.4.4.1 --- Surrogate measurement of sleep in Drosophila --- p.31 / Chapter 1.5 --- Objectives of study --- p.33 / Chapter 2 --- Materials and Methods --- p.35 / Chapter 2.1 --- Preparation of the Sleep Disorder (SD) extract --- p.35 / Chapter 2.2 --- Establishment of the Drosophila sleep model --- p.38 / Chapter 2.2.1 --- Drosophila culture --- p.38 / Chapter 2.2.1.1 --- Fly stock --- p.38 / Chapter 2.2.1.2 --- Fly food --- p.38 / Chapter 2.2.1.3 --- Culture environment --- p.38 / Chapter 2.2.2 --- Preparation of flies for experiments --- p.39 / Chapter 2.2.3 --- Agar food and drug preparation --- p.39 / Chapter 2.2.4 --- Measurement of activity and sleep in fly --- p.40 / Chapter 2.2.5 --- Determining the effects of SD extract on Drosophila sleep --- p.40 / Chapter 2.2.5.1 --- Data analysis --- p.41 / Chapter 2.2.6 --- Test of amount of food intake for different dosages of SD using food dye --- p.41 / Chapter 2.2.7 --- Survival test --- p.42 / Chapter 2.3 --- Establishment of the Drosophila caffeine-induced insomnia model --- p.43 / Chapter 2.3.1 --- Determining the effects of caffeine on the Drosophila sleep --- p.43 / Chapter 2.3.2 --- Determining the effects of SD extract on the Drosophila caffeine-induced insomnia model --- p.43 / Chapter 2.3.2.1 --- HPLC determination of caffeine intake in Drosophila --- p.44 / Chapter 2.3.2.2 --- "Spectrophotometric measurement of caffeine, SD and caffeine-SD solutions" --- p.45 / Chapter 2.4 --- "Expression of Cyp6a8, Djun and Dfos in drug-treated Drosophila heads" --- p.46 / Chapter 2.4.1 --- Drug treatment and collection of fly head samples --- p.46 / Chapter 2.4.2 --- Total RNA extraction from fly heads --- p.46 / Chapter 2.4.3 --- Real-time polymerase chain reaction analysis --- p.48 / Chapter 2.5 --- Determining the effects of SD formula on short-sleep mutants --- p.51 / Chapter 2.5.1 --- Fly stocks --- p.51 / Chapter 2.5.2 --- Experimental design --- p.51 / Chapter 3. --- Results --- p.53 / Chapter 3.1 --- Establishment of the Drosophila sleep model --- p.53 / Chapter 3.1.1 --- Baseline activity and sleep --- p.53 / Chapter 3.1.2 --- Effect of SD on Drosophila sleep --- p.55 / Chapter 3.1.3 --- Amount of food intake for different dosages of SD --- p.57 / Chapter 3.1.4 --- Effect of SD on the survival of wide-type (CSI) flies --- p.59 / Chapter 3.2 --- Establishment of the caffeine-induced insomnia model in Drosophila --- p.61 / Chapter 3.2.1 --- Effect of Caffeine on Drosophila sleep --- p.61 / Chapter 3.2.2 --- Effect of the SD on the caffeine-induced wakefulness --- p.64 / Chapter 3.2.3 --- Validation of caffeine intake by HPLC --- p.68 / Chapter 3.2.4 --- "Spectra of caffeine, SD and caffeine-SD solutions" --- p.72 / Chapter 3.3 --- Effect of SD on the sleep of short-sleep mutants --- p.74 / Chapter 3.3.1 --- fumin mutant --- p.74 / Chapter 3.3.2 --- minisleep mutant --- p.78 / Chapter 3.3.3 --- HkY fly --- p.82 / Chapter 3.4 --- Effect of the SD and caffeine on gene expression --- p.86 / Chapter 3.4.1 --- Effect of the SD and caffeine on Cyp6a8 mRNA expression --- p.86 / Chapter 3.4.2 --- Effect of the SD and caffeine on Djun mRNA expression --- p.89 / Chapter 3.4.3 --- Effect of the SD and caffeine on Dfos mRNA expression --- p.91 / Chapter 4. --- Discussion --- p.93 / Chapter 4.1 --- Rationales for evaluating the effect of SD formula in Drosophila model --- p.94 / Chapter 4.2 --- Establishment of the Drosophila Sleep model --- p.96 / Chapter 4.2.1 --- Hypnotic effect of SD in Drosophila --- p.97 / Chapter 4.2.2 --- Toxicity of SD extract in fly --- p.98 / Chapter 4.3 --- Effect of SD on Drosophila caffeine-induced insomnia model --- p.100 / Chapter 4.3.1 --- Drug administration in Drosophila --- p.102 / Chapter 4.4 --- Effect of SD on Short-sleep mutant --- p.105 / Chapter 4.5 --- Study of gene expression by SD --- p.108 / Chapter 4.6 --- Limitations of the model --- p.112 / Chapter 5. --- Conclusion and Future Prospects --- p.115 / Chapter 5.1 --- Conclusion --- p.115 / Chapter 5.2 --- Future prospects --- p.115 / References --- p.117
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Young adults' beliefs about and use of herbal supplements in relation to their dietary attitudes and behaviorsKoorndyk, Tamberly 14 June 2001 (has links)
Today in the United States, herbal supplements are growing increasingly
popular, however, little is known about the safety and efficacy of these products. This
study contributes to the growing body of information about the prevalence of herbal
supplement use among young adults (18 to 24 years) and the beliefs young adults hold
about herbal supplements in relation to their dietary attitudes and behaviors.
A self-administered, four-part questionnaire was mailed to a geographically
representative sample of 298 young adults (18 to 24 years) residing in Oregon; 205
questionnaires were usable (69% response rate). There was an equal ratio of male and
female respondents, half students and half non-students, the majority being Caucasian
(93%), with a mean age of 21.5 years.
Nearly 60% of the sample reported using herbal supplements (n=122). Thirty-seven
percent were sometime users (less than weekly) and 22% were regular users (at
least weekly). More female respondents reported using herbal supplements (69%) than did male respondents (49%). Respondents who were White or Asian/Pacific
Islander were the only ethnic groups that reported using herbal supplements regularly.
Users were more educated than non-users, however use was very similar among
students and non-students. Herbal supplement use also was very similar between
respondents having different residencies.
Familiarity with different herbs was positively related to level of herbal
supplement use. Regular users were familiar with the greatest number of herbs,
followed by sometime users.
Herbal supplement users tended to have more healthful lifestyle characteristics
than non-users. Frequency of fast food patronage was negatively related to level of
herbal supplement use. The median number of times a fast food restaurant was
patronized was lower among regular users of herbal supplements than among those
who did not use supplements or used them less often. The median number of times
breakfast was eaten also seemed to be slightly higher among regular users than other
groups. Other healthful lifestyle characteristics, such as BMI and drinking in
moderation, did not tend to be more healthful among herbal supplement users. The
results were mixed on smoking behavior. Regular users of herbal supplements were no
more or less likely than non-users to smoke, but non-users were less likely than
sometime users to smoke.
Regular users of herbal supplements tended to think herbal supplements are
useful for certain health parameters more often than sometime users and non-users.
Most regular users of herbal supplements agreed herbs are useful for maintaining good
health (89%) and preventing/treating common illnesses like colds (85%). Almost two-thirds also thought herbs are useful for preventing serious chronic illnesses (61%) and
insuring a well-balanced diet (65%).
Attitudes toward the effectiveness, convenience, and expense of taking herbal
supplements in comparison to eating a balanced diet as ways of staying healthy were
related to herbal supplement use. Herbal supplement users did not appear to have
positive attitudes towards herbs when comparing herbs to a well-balanced diet. Only
11% of users thought that herbs are more effective than diet as ways to stay healthy,
and users were more likely than non-users to think herbs are more expensive ways to
stay healthy. However, both levels of users were more likely to think herbal
supplements are more convenient than diet.
Attitudes about the effectiveness, safety, expense, naturalness, potency, and
personal control of taking herbal supplements in comparison to prescription
medications was related to level of herbal supplement use. In general the trend was
for users to be more likely to have positive attitudes toward herbs and less likely to
give a "don't know" answer.
Eating the recommended number of food guide pyramid servings of fruits and
vegetables as well as eating a greater number of nutrient rich vegetables was not
related to herbal supplement use. However, a somewhat higher percentage of herbal
supplement users tended to meet the fruit and vegetable recommendations than nonusers
of herbal supplements.
Stage of change in relation to vegetable intake was related to herbal
supplement use. As respondents' herbal supplement use increased, so did the
likelihood of classifying themselves into one of the action stages of change for vegetable consumption. Stage of change for fruit consumption was not related to
herbal supplement use.
Choice to stop using herbs if they were pronounced unsafe by a governmental
agency was not related to level of herbal supplement use. However, 17% of sometime
users and 16% of regular users reported that they would continue to use herbs even
after they were pronounced unsafe by a governmental agency.
The results of this study clearly show that there is a high prevalence of herbal
supplement use among young adults in Oregon, and those who are using herbal
supplements seem to have a strong belief in the herbs they are taking. With the
limited knowledge on herbs' safety and efficacy, young adults need to be educated
about the herbs they are using. Hopefully, the information from this study can help
health professionals identify which young adults might be using herbal supplements in
order to educate them on making smart choices about herbs, and smart choices about
their overall health. To inform young adults about the herbs they are using, additional
research on herbal supplements' potential benefits and harmful side effects is needed. / Graduation date: 2002
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The anticancer effects of Yanhusuo San : mechanism of actions studyGao, Jian Li January 2009 (has links)
University of Macau / Institute of Chinese Medical Sciences
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Anti-oxidative and pro-oxidative effects of curcuminoids on cellular senescence in aging and cancerLi, Ying Bo January 2011 (has links)
University of Macau / Institute of Chinese Medical Sciences
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龍血竭的化學成分及廣佛手的化學成分分析研究 / Study on the chemical constituents of Resina Draconis and chemical analysis of Fructus Citri Sarcodactylis楚俊 January 2012 (has links)
University of Macau / Institute of Chinese Medical Sciences
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Icaritin reduces tert-butylhydroperoxide-induced cell damage through activation of Nrf2 and Akt in H9c2 cardiomyoblasts / 淫羊藿素的心肌保護的作用Lei, Si Wan January 2012 (has links)
University of Macau / Institute of Chinese Medical Sciences
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The medicinal value of Amaryllidaceae and Asteraceae species used in male circumcisionDilika, Fikile 11 April 2007 (has links)
Please read the abstract in the section 07chapter7 of this document / Thesis (DPhil (Plant Physiology))--University of Pretoria, 2007. / Plant Science / unrestricted
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Biological activities of medicinal plants traditionally used to treat Septicaemia in the Eastern Cape, South AfricaChinyama, Robert Fred January 2009 (has links)
Over the past 25 years, there has been a resurgence of worldwide scientific research in the fields of ethnopharmacology. The Western world has acknowledged the continued use of traditional medicines by the majority of third world countries, and the need for novel drug development. Hence, much of the pharmaceutical research in recent years has focused on the ethnobotanical approach to drug discovery (Light et al., 2005). In South Africa, as in most developing parts of the world, traditional herbal medicine still forms the backbone of rural healthcare. The government health services in South Africa provide only western medical care although the majority of the population consult traditional healers for some or all of their healthcare needs (McGaw et al., 2005). Medicinal plants like Harpephyllum caffrum are used as blood purifiers or emetics (Watt and Breyer-Brandwijk, 1962), and also for treating acne and eczema. The antimicrobial activity of this plant can be used to treat septicaemia, which is ranked the sixth leading cause of death among neonates and the eighth leading cause of death for infants through the first year of life (Heron, 2007). In this study, the plants investigated for antimicrobial activity were Harpephyllum caffrum, Hermannia cuneifolia, Chironia baccifera, Rhigozum obovatum, Felicia muricata and Pentzia incana. These plants were tested against ATTC (American Type Culture Collection) strains and microorganisms isolated from clinical isolates of patients suffering from septicaemia. The assay methods used included the agar diffusion method using the Mast multipoint inoculator, the microtitre dilution method were used to determine the minimum inhibitory concentration, thin layer chromatography fingerprints accompanied by bioautographic assay were used to detect the inhibition of bacterial growth by active compounds separated from plant extracts and the Ames test was required to assess the possibility of bacterial mutagenesis upon the exposure to plant extracts which can lead to carcinogenicity. In agar diffusion method, extracts of Harpephyllum caffrum inhibited nine strains of Candida albicans, three species of Acinetobacter and four strains of E.faecalis. Extracts of Hermannia cuneifolia inhibited four strains of B.cereus and three strains of Staphylococcus aureus. Extracts of Chironia baccifera inhibited one strain of Acinetobacter and five strains of E.faecalis. Extracts of plants Rhigozum obovatum, Felicia muricata, and Pentzia incana showed no antimicrobial activity. In the microtitre dilution method used to determine the minimum inhibitory concentration (MIC), the results were different from the agar diffusion method. More activity was observed. Extracts of Harpephyllum caffrum inhibited three strains of E.coli, six strains of S.aureus, three species of Acinetobacter and one strain of Klebsiella pneumonia. Extracts of Hermannia cuneifolia inhibited four strains of B.cereus, three strains of S.aureus, two strains of K.oxytoca and one species of Acinetobacter. Extracts of Chironia baccifera inhibited three strains of S.aureus, one strain of MRSA, one species of Acinetobacter and one strain of S.haemolyticus. The MIC values ranged from 0.049 to 6.25mg/ml. Using the thin layer chromatography fingerprints, bioautography showed the presence of various inhibitory chemical compounds. Methanol and acetone extracts of Harpephyllum caffrum, separated very well and showed various inhibition zones on exposure to Candida albicans, Enterococcus faecalis and Staphylococcus aureus. The different inhibition zones were recorded as Rf In the Ames test (Maron and Ames, 1983) the methanol and acetone extracts of Harpephyllum caffrum and Hermannia cuneifolia were negative which means they were devoid of any mutagenic properties. Methanol extracts of Harpephyllum caffrum showed similar results in the Ames assay as reported by Verschaeve and Van Staden (2008). values ranging from 0.25 to 0.95. The zones indicate the different inhibiting chemical compounds present in the plant. Petroleum ether, ethyl acetate, chloroform and formic acid were the solvents used in the assay in the ratio 8:7:5:1, respectively. Establishing the antimicrobial activity of these plants contribute to the systematic scientific investigation of indigenous South African medicinal plants.
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Exploration of the anticancer mechanisms of novel chemotherapeutic adjuvants involving autophagy and immune system reprogramming in the treatment of pancreatic cancerZhang, Zhu 11 June 2020 (has links)
Pancreatic cancer is known to be one of the most life-threatening cancers characterized by aggressive local invasion and distant metastasis. The high basal level of autophagy in pancreatic cancer may be responsible for the low chemotherapeutic drug response rate and poor disease prognosis. However, the clinical application of autophagy inhibitors was unsatisfactory due to their toxicity and minimal single-agent anticancer efficacy. Hence, oncologists begin to consider the tumor microenvironment when exploring new drug targets. In the present study, the anti-tumorigenic mechanisms of two major phytochemicals derived from Chinese medicinal herbs had been investigated against pancreatic cancer development. Calycosin is a bioactive isoflavonoid of the medicinal plant Astragalus membranaceus. Our results have shown that calycosin inhibited the growth of various pancreatic cancer cells both in vitro and in vivo by inducing cell cycle arrest and apoptosis. Alternatively, calycosin also facilitated MIA PaCa-2 pancreatic cancer cell migration in vitro and increased the expression of epithelial-mesenchymal transition (EMT) biomarkers in vivo. Further mechanistic study suggests that induction of the Raf/MEK/ERK pathway and facilitated polarization of M2 tumor-associated macrophage in the tumor microenvironment both contribute to the pro-metastatic potential of calycosin in pancreatic cancer. These events appear to be associated with calycosin-evoked activation of TGF-β signaling, which may explain the paradoxical drug actions due to the dual roles of TGF-β as both tumor suppressor and tumor promoter in pancreatic cancer development under different conditions. Isoliquiritigenin (ISL) is a chalcone obtained from the medicinal plant Glycyrrhiza glabra, which can be a precursor for chemical conversion to form calycosin. Results have shown that ISL decreased the growth and EMT of pancreatic cancer cells in vitro, probably due to modulation of autophagy. ISL-induced inhibition of autophagy subsequently promoted reactive oxygen species (ROS) production, leading to induction of apoptosis in pancreatic cancer cells. Such phenomenon also contributed to the synergistic growth-inhibitory effect in combined treatment with the orthodox chemotherapeutic drug 5-fluorouracil. In addition, ISL-induced tumor growth inhibition in vivo was further demonstrated in a tumor xenograft mice model of pancreatic cancer. ISL promoted apoptosis and inhibited autophagy in the tumor tissues. Study on immune cells indicates that ISL could reduce the number of myeloid-derived suppressor cells (MDSCs) both in tumor tissue and in peripheral blood, while CD4+ and CD8+ T cells were increased correspondingly. In vitro test has revealed that ISL inhibited the polarization of M2 macrophage along with its inhibition of autophagy in M2 macrophage. These immunomodulating effects of ISL had reversed the pro-invasive role of M2 macrophage in pancreatic cancer.In conclusion, calycosin acts as a "double-edged sword" on the growth and metastasis of pancreatic cancer, which may be related to the dual roles of TGF-β and its influence on the tumor microenvironment. Alternatively, ISL consistently inhibited the growth and metastatic drive of pancreatic cancer through regulation of autophagy and reprogramming of the immune system. The differential modes of action of these compounds have provided new insights in the development of effective pancreatic cancer treatment adjuvants.
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