Colorectal cancer (CRC) is the third most prevalent and second leading causes of cancer-associated deaths globally. Over the last few decades, ent-kaurane diterpenes have been widely investigated for their anticancer potentials. Flexicaulin A (9) is a naturally occurring ent-kaurane. Previously, our lab modified the structure of 9 by replacing the C-11 hydroxyl group with carbonyl group and obtained a novel compound oxoflexicaulin A (11). However, anticancer activities and mechanistic pathway of these two compounds are yet to be explored. In the current thesis, we evaluated the cytotoxicity of compounds 9 and 11 in A549 lung, A375 melanoma, PANC1 pancreatic, HCT-116 and HT-29 colon cancer and 293T human embryonic kidney cells as well as compared the activity with a number of known natural ent-kauranes to describe their structure-activity relationship. Our study found that the presence of α, β-unsaturated ketone groups in ent-kaurane structure acted as the pharmacophore. The replacement of C-11 hydroxyl group by carbonyl in 9 (IC50: 3.68 µM) gives a novel potent anticancer compound 11 (IC50: 0.77 µM). Considering the novelty and superior activity of 11, its mechanistic pathway was studied in HCT-116 cells and compared with the natural scaffold 9. Flow cytometry analysis by Annexin V/PI staining along with fluorescent staining by DAPI showed that both compounds induced apoptosis in HCT-116 cells. Induction of apoptosis is mediated through up-regulation of tumor suppressor protein p53 and pro-apoptotic protein Bax, Bak and puma as well as promoting the cleavage of PARP while down-regulation of anti-apoptotic protein Bcl-2 and PARP. Apart from their effect on apoptosis, compounds 9 and 11 stimulated the event of senescence, a process of cellular aging, as confirmed by β-galactosidase assay. Induction of senescence is related with up-modulation of p21 and p27 while down-modulation of p16, Rb and its transcription factor E2F1. Moreover, immunofluorescence staining showed translocation of p21 and p27 from the cytoplasm to nucleus after treatment with 9 and 11. Further study found that the two ent-kauranes inhibited the protein level of two NF-κB sub-units p65 and p50 in the nucleus as well suppressed the cytoplasmic level of NF-κB inhibitor IkB-α. Both compounds also inhibited the expression and phosphorylation of STAT3 in the cytoplasm and nucleus, so as for the expression and phosphorylation of Src, an up-stream kinase of STAT3. In xenograft nude mice model, compound 11 remarkably inhibited tumor growths (volume and size) but the body weights of the mice were also reduced (p < 0. 05). Therefore, we designed to synthesis a series of prodrug analogs from 11 by adding acetal protecting group to reduce the toxicity. One of the prodrug (37) significantly attenuated the tumor volume and size (p < 0.05) at 50 mg/kg without any toxicity (p > 0.05). The prodrug 37 is actually released as compound 11 in the mice due to its cleavage in the acidic microenvironment of tumor. Taken together, antitumor effect of compound 11 in CRC model is supposed to be mediated through induction of apoptosis and senescence via modulation of NF-κB and STAT3 signaling pathway. Keywords: Colorectal cancer, ent-kaurane, flexicaulin A, oxoflexicaulin A, cytotoxicity, anticancer, apoptosis, pathway, NF-κB, STAT3.

To determine whether the three Siegesbeckia plants can all serve as the origins of HS, we compared their fingerprint chromatograms and inhibitory effects on inflammatory mediators. Chemical analyses showed that the three species have different profiles, although they have common peaks in their fingerprint chromatograms. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) of the common peaks demonstrated that all samples of the three species tend to be species-dependently grouped and separated. Ten components contributing to the species discrimination were identified, of which 8 are long-chain fatty acids/esters, and 2 are darutoside and hythiemoside A. Inhibitory effects of the three species on NO production and IL-6 secretion in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages are different, with SG being the most and SP the least potent. These chemical and bioactivity assays support the notion that the three Siegesbeckia species cannot be equally used as the plant origins of HS.;This work provides a chemical and pharmacological basis for determining whether the three Siegesbeckia genus herbs SP, SO and SG can all serve as the origins of HS; and also provides pharmacological justifications for the clinical application of HS in treating inflammatory disorders.

Die Broschüre stellt eine Auswahl von Pflanzen vor, die im Haus- und Kleingarten problemlos angebaut werden können, um daraus Kräutertee zuzubereiten. Besonders eingegangen wird auf die unterschiedlichen Zubereitungsformen der einzelnen Pflanzenteile und auf die Heilwirkung von Kräutertees. In der 2., überarbeiteten Auflage wurden seltene Teepflanzen und Pflanzen mit besonderer Süßkraft aufgenommen.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Background: The current treatment for HIV/AIDS is called highly active antiretroviral therapy (HAART) and is a combination of anti-HIV reverse transcriptase inhibitors and protease inhibitors. HAART is capable of suppressing HIV replication and subsequently improving the patients’ survival. However, the issues associated with use of HARRT such as the high cost, severe side-effects, and drug resistance have called for development of alternative anti-HIV therapeutic strategies. In this study, we screened several traditional Chinese medicinal herbal extracts for their anti-HIV activities and determined their anti-HIV mechanisms. Methods: Nine traditional Chinese medicinal (TCM) herbal plants and their respective parts derived from Hainan Island, China were extracted using a series of organic solvents, vacuum dried, and dissolved in dimethyl sulfoxide. Initial anti-HIV activity and cytotoxicity of these extracts were evaluated in HIV-infected human CD4+ T lymphocytes Jurkat. Extracts of higher anti-HIV activities and lower cytotoxicity were selected from the initial screening, and further examined for their effects on HIV-1 entry, post-entry, reverse transcriptase, gene transcription and expression using combined virology, cell biology and biochemistry techniques. Results: Four extracts derived from two different herbal plants completely blocked HIV-1 replication and showed little cytotoxicity at a concentration of 10 g/ml. None of these four extracts had any inhibitory effects on HIV-1 long terminal repeat promoter. Two of them exhibited direct inhibitory activity against HIV-1 reverse transcriptase (RT). All four extracts showed significant blocking of HIV-1 entry into target cells. Conclusions: These results demonstrated that four TCM extracts were capable of preventing HIV-1 infection and replication by blocking viral entry and/or directly inhibiting the RT activity. These results suggest the possibility of developing these extracts as potential anti-HIV therapeutic agents.

This was a chemical laboratory study. The main focus was to evaluate the chemical stability of Hypericum perforatum (St John's wort), Ginkgo biloba and Piper methysticum (Kava Kava) under unfavourable environmental conditions. Different dosage forms representing the same amount of active ingredients for each were used. Some of the dosage forms were self manufactured according to Good Manufacturing Practice. Samples of the dried powder of each plant was also exposed to a series of gamma¬radiation. Acetone was used as an extractant for all three plants, after evaluating and discarding the extraction method stipulated in the British Herbal Pharmacopoeia. Identification of the different plants were carried out by means of Thin Layer Chromatography. The in-house developed mobile phases EMW, BEA and CEF, showed better separation and visibility compared to the mobile phases used in the British Herbal Pharmacopoeia. The plates were sprayed with either vanillin or p-anisaldehide for optimal visualization of the separated compounds. After the specified period of 6-months, comparative TLC was performed on all samples. This was achieved for each plant by applying all samples stored at a specific condition i.e.25°C, on the same plate. The samples were stored at low temperature after exposure to the specific time interval. Quantitative analysis was performed by spectrophotometry, and high pressure liquid chromatography. The data obtained from these analytical methods, were used to evaluate the relative chemical stability of each dosage form. The relationship between the quantitative data and the qualitative changes in the TLC fingerprints, were compared, hoping to achieve a common pattern relating to the stability. The order of the reaction as well as the reaction rate constant (k) for each dosage form was calculated, except for kava kava. The shelf-life (too) was calculated using the analyzed data obtained by spectrophotometry or HPLC. The relevance of conventional pharmaceutical calculations in the prediction of shelf-life, by means of accelerated stability tests, was investigated for the possible application to herbal products. The effects of gamma radiation on the degradation of the chemical compounds present in each plant, was evaluated. After an evaluation of all the relevant data, it seemed that the tablet-dosage forms were equally effective regarding stability, compared to the capsules. Liquid extracts appeared to be less stable than the extract capsules. The extract capsules seemed to degrade more rapidly than the herbal tablets or herbal capsules. Exposure to low dose radiation (4.4 kGy) did not seem to have an influence on the stability. It was evident that some herbs were more sensitive to sunlight or heat than others. In general, all three of the chosen plants seemed to be relatively stable if stored in the specified conditions. It seemed valid for the shelf-life to be expressed as two years. / Dissertation (MSc (Pharmacology))--University of Pretoria, 2001. / Pharmacology / unrestricted

Please read the abstract in the section 00front of this document. / Dissertation (MSc (Pharmacology))--University of Pretoria, 2003. / Pharmacology / unrestricted

There has been a tremendous growth in popularity in the use of herbs especially those designed to assist with mental wellness and to reduce psychological ailments. Clients' widespread usage of medicinal herbs for psychologically related symptoms has created a need for psychologists to become more informed about the health risks associated with taking medicinal herbs. It is important that psychologists be familiar with the most current information regarding medicinal herbs to be able to initiate discussions about medicinal herbs with their clients to help mitigate potential health risks. This study was conducted to increase knowledge about psychologist's perceptions and knowledge about medicinal herbs and about psychologist's practices regarding discussions and recommendation of medicinal herbs with their clients. A total of 1963 questionnaires were responded to by licensed psychologists in the state of California. Most psychologists felt they either did not have enough knowledge or that more knowledge was needed about medicinal herbs. The results show that there is a positive association between psychologist's perceived knowledge of medicinal herbs and their willingness to initiate discussions about them. It was also shown that the more perceived knowledge of medicinal herbs by psychologists, the more willing the psychologists were to recommend them. There was hesitancy among some psychologists to talk about herbs as they felt they either did not have the expertise or that it was beyond the scope of their practice to do so. As many medicinal herbs have significant pharmacological activity and thus potential adverse effects and drug interactions, psychologists should be familiar with herbs, their therapeutic modalities, and safety, so they will be better able to discuss these issues with their clients.

No description available.

Thesis (M.Sc. Agriculture (Horticulture)) -- University of Limpopo, 2017 / Artemisia annua L. from the family Asteraceae is an annual medicinal plant and has been used to make herbal remedies in Asia for thousands of years. Artemisinin is a sesquiterpene lactone, isolated from aerial parts of Artemisia annua, with the highest concentrations being in flowers and leaves. In addition to potent anti-malarial activity, artemisinin possesses anti-cancer, anti-schistosomiatic, anti-hepatitis B, anti-HIV, anti-leishmanial and herbicidal activities. Low artemisinin production (0.01-2%) from A. annua is a major constraint in commercialisation of the drug for control of malaria. Worldwide, efforts have been underway to improve the concentration of artemisinin using conventional breeding, biochemical, physiological, molecular and hairy-root culture techniques, however all these methods are not economical. Cultural practices like spacing and pruning have limitation in improving artemisinin concentration and these may help in increasing the concentrations of artemisinin. Study was conducted at the experimental farm of the Agricultural Research Council – Vegetable and Ornamental Plants, Roodeplaat Pretoria. The objective of this study was to determine whether spacing, pruning and their interactions would have any effect on the concentrations of artemisinin, growth and yield of A. annua and whether drying methods would have an effect on the concentrations of artemisinin in A. annua. Since there was only one field trial, all sub-objectives were addressed at once (Chapter 3). Fresh seeds of A. annua were obtained from the ARC-VOP gene bank and sown in seedling trays in September 2014. Uniform eight-week-old seedlings were hardened-off, transplanted in November 2014 in 10 cm deep holes and then pruned ten weeks after transplanting. Treatments for Experiment 1, viz., 3 × 4 factorial experiment were laid out in a randomised complete block design, with four replications (n = 48). The two factors of the experiment were (a) spacing [0.5 × 1 m2 (standard: 0.50 m2), 0.5 × 0.7 m2 (small: 0.35 m2) 0.5 × 0.5 m2 (smaller: 0.25 m2) and 0.3 × 0.7 m2 (smallest: 0.21 m2)] and (b) pruning [no pruning (control), removing the apical bud and removing shoots three nodes from the bottom]. The plants were irrigated using overhead sprinklers system for two hours three times per week. Four readings for growth variables (plant height, stem diameter and chlorophyll content) were collected with one week interval. Plants were harvested after 180 days from planting, and leaves, stems and roots were separated weighed and oven dried at 40 ºC for 72 h. In Experiment 2 (drying methods), treatments, namely, 100% sun, 100% shade, 50% shade, freeze and oven drying were arranged in completely randomised design with four replicates (n = 20). The treatments were exposed for a week, to full sunlight, 50% shade-drying under a shade net that allows 50% light penetration, 100% shade under enclosed room at ambient (24-25 ºC) temperature, oven drying for 24 h at 40 ºC, and freeze-drying for three days. Freeze-drying had significant effect on artemisinin concentration of 1.941%. It was followed by oven (1.738%) and 100% shade drying (1.657%) and the lowest artemisinin concentration (1.412%) was obtained from 50% shade drying. The smaller spacing of 0.25 m2 in combination with apical bud removal had a significant effect on artemisinin concentration, producing artemisinin concentration of 0.193%. Spacing had a significant effect on stem diameter, fresh leaf mass and dry leaf mass but had no effect on plant height and chlorophyll content. Pruning had a significant effect on plant height and chlorophyll content and had no effect on stem diameter. The small spacing of 0.35 m2 had the highest fresh and dry leaf mass of 17.99 and 9.62 t/ha. The interaction of spacing and pruning had no significant effect on the growth and yield of A. annua. The results from this study suggested that cultural and processing practices may have direct effects in the concentration of artemisinin, growth and yield of A. annua. The results xiv provided some understanding on how agronomic and processing practices can be used to increase artemisinin content in A. annua and understand the interaction between different agronomic practices and thereby allowing the development of economic methods for A. annua post-harvest handling. Future work should focus on implementing various pruning techniques to trigger stress and indirectly secondary metabolites