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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Changes in interorgan lipid handling underlie the decrease in adiposity of bitter melon supplemented diet-induced obese rats

Chan, Lui-yan. January 2007 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.
12

Mechanistic and functional characterization of bitter melon extract (BME) and its bioactive component, MAP30, in combating ovarian cancer oncogenesis and chemoresistance

Yung, Ming-ho, 容銘浩 January 2013 (has links)
Ovarian carcinoma is one of the most leading causes of cancer death among all gynaecologic malignancies worldwide. Although there are advances in cancer treatment for the last decades, the curative rate of this disease is just modestly improved. Chemoresistance is the major obstacle in clinical management of ovarian cancer nowadays. Thus, it is an urgent need for exploring effective alternative therapeutic strategies for ovarian cancer patients with advanced or recurrent disease. Emerging evidence has suggested that targeting cancer cell metabolism is the most promising molecular therapeutic approach in combating human cancers. Recently, the application of pharmaceutical AMPK activators is a plausible approach in selectively and specifically killing cancer cells without hampering normal cells. However, these pharmaceutical AMPK activators have many side-effects. Therefore, searching for replaceable reagents from nutraceuticals is a “new vista”. Bitter melon and its bioactive components are proposed to be natural activator of AMPK not only to reduce triglycerides levels in hyperlipidemic diabetic or insulin-resistant rodents but also to suppress human cancer cell growth specifically without toxicity to normal cells. In this study, the anti-cancer effect and molecular mechanism of bitter melon extract (BME) and one of its bioactive components, MAP30, on ovarian cancer cells were examined. Upon treatment of BME and MAP30, ovarian cancer cells showed a drastic reduction in cell proliferation and an increase of cell apoptosis in a dose dependent manner. Intriguingly, co-treatment of BME or MAP30 could enhance cisplatin-induced cell cytotoxicity in ovarian cancer cells. On the other hand, tumor microenvironement has been known as a key factor promoting cancer progression and chemoresistance. Results herein showed that BME or MAP30 could inhibit cell growth, cell migration and invasion of ovarian cancer cells mediated by omentum conditioned medium (OCM), as well as enhanced cisplatin-mediated cell cytotoxicity in a xenograft mouse tumour model. Mechanistic studies revealed that the inhibitory effect of BME and MAP30 was concomitantly associated with up-regulated AMPK activity but reduced expression of phospho-AKT, phospho-ERK and FOXM1. Such effects were similar to the functions of common AMPK activators e.g. AICAR, A23187, metformin or hypoxic stress, indicating that BME and MAP30 functions as natural AMPK activators in suppressing cancer cells growth through activating AMPK activity and inhibiting AKT/ERK/FOXM1 signaling cascade. Importantly, this study demonstrated that BME and MAP30 induced AMPK activation through an AMP-independent manner using a pair of isogenic HEK293 cells with overexpression of either the wild-type (WT) or R531G mutant isoform of AMPK2 subunit, implying the significance that BME and MAP30 may not affect the mitochondrial respiration and thus may be more tolerated by patients when used as anti-cancer medications. Taken together, the findings in this study suggest that the non-toxic BME and MAP30 function as natural AMPK activator in impairing ovarian cancer cell growth and enforcing cisplatin-mediated cell cytotoxicity in ovarian cancer cells through targeting cancer cell metabolism. Thus, BME or MAP30 may be used as a supplement for synergistically enhancing the efficacy of current chemotherapy regimes. / published_or_final_version / Obstetrics and Gynaecology / Doctoral / Doctor of Philosophy
13

The effects of Momordica charantia and cinnamon extracts on glucose uptake and adiponectin secretion in 3T3-L1 adipose cells /

Roffey, Ben. January 2006 (has links)
To examine the effects of Momordica charantia (MC) and cinnamon on glucose uptake and adiponectin secretion (AS) fat cells, 3T3-L1 adipocytes were treated with a water extract of cinnamon (CE) and three concentrations of MC water and ethanol extracts. The treatment combination of 0.2 mg/ml MC water extract and 0.5 nM insulin was associated with an increased glucose uptake into the cells (61%) and increased AS from the cells (75%). Without insulin, 0.2 mg/ml of CE increased glucose uptake (100%) and completely inhibited AS from the cells. Sub-optimal concentrations of insulin did not further enhance the CE activity and, in combination with 50 nM insulin, a dose-dependent decrease in glucose uptake was observed. The present results indicate that preferentially water-soluble component(s) in MC enhance the glucose uptake action of sub-optimal concentrations of insulin in 3T3-L1 adipocytes. This effect is accompanied by and may be a result of increased AS. CE increases glucose uptake in these adipocytes but inhibits AS.
14

Palatability of bitter melon and the effect of health information on consumption intentions : a pilot study

Snee, Laura Stacey January 2006 (has links)
Thesis (M.S.)--University of Hawaii at Manoa, 2006. / Includes bibliographical references (leaves 81-90). / viii, 90 leaves, bound col. ill. 29 cm
15

Changes in interorgan lipid handling underlie the decrease in adiposity of bitter melon supplemented diet-induced obese rats /

Chan, Lui-yan. January 2007 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available online.
16

Investigação do efeito da Momordica charantia L. no controle glicêmico e na renoproteção de ratos com nefropatia diabética submetidos à manobra da isquemia e reperfusão renal / Investigation of the effect of Momordica charantia L. on glycemic control and renoprotection of rats with diabetic nephropathy submitted to renal ischemia and reperfusion maneuvers

Marcellino, Márcia Clélia Leite 29 March 2018 (has links)
Submitted by Marcia Clelia Leite Marcellino (marcia.clelia@terra.com.br) on 2018-06-11T02:33:02Z No. of bitstreams: 1 TESE IMPRESSÃO.pdf: 1297621 bytes, checksum: 72d61d4f45d3f68457e648dba38bd91f (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2018-06-13T16:42:35Z (GMT) No. of bitstreams: 1 marcellino_mcl_dr_bot.pdf: 1297621 bytes, checksum: 72d61d4f45d3f68457e648dba38bd91f (MD5) / Made available in DSpace on 2018-06-13T16:42:35Z (GMT). No. of bitstreams: 1 marcellino_mcl_dr_bot.pdf: 1297621 bytes, checksum: 72d61d4f45d3f68457e648dba38bd91f (MD5) Previous issue date: 2018-03-29 / A nefropatia diabética é fator de risco para aumento da morbimortalidade em pessoas submetidas à cirurgia. A investigação por tratamentos capazes de exercer proteção renal durante procedimentos anestésico- cirúrgicos tornam-se relevantes. Este estudo avaliou a glicemia, a variação ponderal, a concentração sanguínea de ureia e creatinina, a proteinúria, a microscopia eletrônica dos rins com e sem isquemia e reperfusão, e a proteção renal de ratos Wistar com nefropatia diabética experimental, tratados previamente com a infusão dos frutos da Momordica charantia L.. Utilizamos 26 ratos Wistar, divididos em: Grupo Controle (n=10); Grupo Diabético sem tratamento (n=8) e Grupo Diabético tratados com Momordica charanthia L. (n=8). A determinação da glicemia de ambos os grupos foi feita com glicosimetro e o peso foi mensurado em balança digital no 1º, 15º e 30º dia do experimento. A dosagem da proteinúria foi feita em urina de 24 horas. Previamente a eutanásia, foi realizada a manobra da isquemia por 30 minutos, seguida da reperfusão por 15 minutos, no rim esquerdo, simulando a lesão renal ocorrida em cirurgias. Os rins isquêmicos e não isquêmicos foram encaminhados para microscopia eletrônica. A obtenção do sangue para dosagem de ureia e creatinina foi feita por punção cardíaca. Os resultados obtidos evidenciaram redução significativa da glicemia (p<0,001- Teste Friedman p<0,05) no 15ª dia, nos animais diabéticos tratados com a planta, Não foi evidenciada alterações significativas no peso dos animais. A Momordica charantia L. reduziu significativamente a concentração de creatinina (p=0,022 – Teste T-Student p<0,05) e a proteinúria (p<0,001 – Teste T-Student p<0,05), mas não interferiu na uremia dos animais diabéticos. Na microscopia eletrônica evidenciou-se nos rins isquêmicos e não isquêmicos do grupo diabético tratado, a preservação da membrana basal, podócitos e pedicelos. Estas estruturas foram lesionadas no grupo diabético sem tratamento. Conclui-se que a Momordica charantia L. mostrou-se eficaz na redução da glicemia, no 15º dia de experimentação; reduziu a creatinina e a proteinúria em relação ao grupo diabético sem tratamento e preservou a integridade de estruturas glomerulares, sugerindo renoproteção frente à hiperglicemia persistente e a manobra de isquemia e reperfusão renal. / Diabetic nephropathy is a risk factor for increased morbidity and mortality in people undergoing surgery. The investigation of treatments capable of exerting renal protection during anesthetic-surgical procedures becomes relevant. Diabetic nephropathy is a risk factor for increased morbidity and mortality in people undergoing surgery. The investigation of treatments capable of exerting renal protection during anesthetic-surgical procedures becomes relevant. This study evaluated glycemia, weight variation, blood urea and creatinine concentration, proteinuria, electron microscopy of the kidneys with and without ischemia and reperfusion, and renal protection of Wistar rats with experimental diabetic nephropathy, previously treated with the infusion of the fruits of Momordica charantia L. We used 26 Wistar rats, divided into: Control Group (n = 10); Untreated Diabetic Group (n = 8) and Diabetic Group treated with Momordica charanthia L. (n = 8). The determination of glycemia was done with glycosimetre and the weight was measured in digital scale on the 1st, 15th and 30th day of experimentation. The proteinuria was measured in 24-hour urine. Before euthanasia, the maneuver of the ischemia was performed for 30 minutes, followed by reperfusion for 15 minutes in the left kidney, simulating the renal injury that occurred in surgeries. The ischemic and non-ischemic kidneys were referred for electron microscopy. The blood obtained for urea and creatinine dosing was done by cardiac puncture. The results obtained evidenced a significant reduction of glycemia (p <0.001 Friedman test p <0.05) on the 15th day, in the diabetic animals treated with the plant. No significant changes were observed in the weight of the animals. Momordica charantia L. significantly reduced creatinine concentration (p = 0.022 - Student's T-test p <0.05) and proteinuria (p <0.001 - Student's T-test p <0.05) but did not interfere with uremia of diabetic animals. Electron microscopy revealed preservation of the basement membrane, podocytes and pedicels in the ischemic and non-ischemic kidneys of the treated diabetic group. These structures were injured in the diabetic group without treatment. It was concluded that Momordica charantia L. was effective in the reduction of glycemia, on the 15th day of experimentation; reduced creatinine and proteinuria in relation to the untreated diabetic group and preserved the integrity of glomerular structures, suggesting renoprotection against persistent hyperglycemia and renal ischemia and reperfusion maneuver.
17

Caracterização química e avaliação de atividade biológica dos metabólitos de actinobactéria endofítica isolada de Momordica charantia L

MELO, Janaína Gonçalves da Silva 05 July 2013 (has links)
Submitted by Luiz Felipe Barbosa (luiz.fbabreu2@ufpe.br) on 2015-04-17T14:43:23Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE Janaina Melo.pdf: 5414983 bytes, checksum: a963ac9ef063b643800d3cd3356538ea (MD5) / Made available in DSpace on 2015-04-17T14:43:23Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE Janaina Melo.pdf: 5414983 bytes, checksum: a963ac9ef063b643800d3cd3356538ea (MD5) Previous issue date: 2013-07-05 / CNPq / Endofíticos são micro-organismos que colonizam o interior das plantas sem aparentemente causar danos ao seu hospedeiro, sendo encontrados em órgãos e tecidos vegetais como folhas, ramos e raízes. Em geral produzem metabólitos secundários de interesse farmacológicos, como também aplicáveis no controle biológico de pragas e doenças. O presente trabalho teve como objetivo investigar a atividade biológica e a caracterização química dos metabólitos secundários do Streptomyces sp. UFPEDA 3345 endofítico isolado de folhas de Momordica charantia L.. A fermentação em cultivo submerso desta linhagem apresentou como melhores condições para produção de metabólitos bioativos o meio M1 com 72 horas de cultivo em pH alcalino. Os extratos acetoetílico do líquido metabólico (EBLM) e o metanólico da biomassa (EBB) foram submetidos aos ensaios de citotoxicidade frente a células tumorais, à avaliação do potencial hemolítico em eritrócitos de camundongos, toxicidade aguda, determinação da concentração mínima inibitória (CMI) e à prospecção química. O extrato metanólico da biomassa (EBB) foi cromatografado em coluna de sílica gel e a fração F4 foi analisada através de cromatografia líquida de alta eficiência (CLAE) resultando na obtenção de três subfrações C1, C2 e C3. Para a atividade citotóxica frente às linhagens HT-29 (carcinoma de cólon), HEp-2 (carcinoma de laringe), NCI-H292 (carcinoma de pulmão) e MCF-7 (carcinoma de mama) na dose única de 50 μg/mL, os extratos, frações e subfrações apresentaram percentual de inibição do crescimento celular entre 17 e 93%. Após a administração da dose de 2.000 mg/kg do extrato EBB em camundongos, não foram observados efeitos tóxicos, sinais visíveis de toxicidade sistêmica e morte dos animais. Quanto ao potencial hemolítico dos extratos, estes apresentaram concentração efetiva de CE50 > 500 μg/mL e não promoveram danos à membrana eritrocitária. As amostras apresentaram atividade antimicrobiana para bactérias Gram-positivas, Gram-negativas, bactéria álcool ácido resistente, fungo filamentoso, leveduras e fitopátogenos. O extrato EBLM apresentou valores de CMI menores para B. subtilis (15,62 μg/mL), M. luteus (7,8 μg/mL) e M. smegmatis (15,62 μg/mL) em comparação ao extrato EBB. A CMI para A. niger, C. albicans e C. krusei os valores variaram de 15,62 a 250 μg/mL. A fração F4 e a subfração C1 apresentaram valores de CMI iguais de 62,5 μg/mL para C. albicans, A. niger e M. smegmatis. Quanto aos valores de CMI dos extratos EBLM e EBB frente a fungos e bactérias fitopatogênicos variaram entre 15,62 a 500 μg/mL. A prospecção química demonstrou a presença de açúcares redutores, compostos fenólicos, mono/sesquiterpenos, triterpenos e esteróides. Os resultados evidenciam que a linhagem endofítica Streptomyces sp. UFPEDA 3345 produz diferentes biomoléculas com diversas atividades biológicas.
18

The effects of Momordica charantia and cinnamon extracts on glucose uptake and adiponectin secretion in 3T3-L1 adipose cells /

Roffey, Ben. January 2006 (has links)
No description available.
19

Maturação, armazenamento e metabolismo da parede celular de diferentes variedades de melões / Maturation, storage and cell wall metabolism of different melon varieties

Pontes, Felipe Moura 23 February 2017 (has links)
Submitted by Socorro Pontes (socorrop@ufersa.edu.br) on 2017-07-03T12:45:48Z No. of bitstreams: 1 FelipeMP_TESE.pdf: 4332703 bytes, checksum: e3baec2dfb0ab1f445aa9af24d9c5566 (MD5) / Approved for entry into archive by Vanessa Christiane (referencia@ufersa.edu.br) on 2017-07-03T14:27:27Z (GMT) No. of bitstreams: 1 FelipeMP_TESE.pdf: 4332703 bytes, checksum: e3baec2dfb0ab1f445aa9af24d9c5566 (MD5) / Made available in DSpace on 2017-07-03T14:27:44Z (GMT). No. of bitstreams: 1 FelipeMP_TESE.pdf: 4332703 bytes, checksum: e3baec2dfb0ab1f445aa9af24d9c5566 (MD5) Previous issue date: 2017-02-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Fruit flesh firmness has a close relation with the cell wall compounds, thus, a higher knowledge about the metabolism of such compounds is indispensable to aspects related to flesh texture change. In the case of melon, the study of flesh firmness is facilitated since it has a great variability, whose amplitude allows a better observation of differences between biochemistry phenomena of cell wall. For that reason, the present work aimed to evaluate the comportment of the varieties acidulus (access 16), momordica (access 2), inodorus (cv. Iracema) and cantalupensis (cv. Olympic), related to maturation and storage of the fruits. Therefore, two experiments were installed. At first one, about maturation, fruits were obtained from determined harvest times by flower anthesis, and a completely randomized design for each mentioned variety was set. In the second one, melons of acidulus, momordica and inodorus varieties were stored in cooler with humidity control (9±1 °C e 85±5%), and evaluated from fruit samples randomLy picked, on a determined time according to each variety durability. For both experiments, fruits were evaluated to physical and chemical characteristics; to the pectinases activity of pectin methylestarese, poligalacturonase and betagalactosidase; and pectin content in three solubilization levels: water soluble, chelate soluble and sodium carbonate soluble. The adequate harvest day for each melon was, 35 days after anthesis for cv. Iracema, 30 days for cv. Olympic, 30 days for access 16 and 20 days for access 2. During maturation, it was observed high flesh firmness of access 16, when compared to remain fruits evaluated, due to its low betagalactosidase activity, as well as its upkeep of chelate and sodium carbonate pectin. Access 2 showed a high decrease in firmness, followed by the tissue cracking at the end of maturation; such an event was consecutive of the water soluble pectin increase and decrease of the chelate and sodium carbonate soluble pectins, with a raise of all pectinases at the maturation ending. Access 16 and the yellow melon (cv. Iracema) has storage potential of 30 days, in refrigerated storage. Access 2, at same conditions, had durability of 10 days. The firmness loss of all studied melons types has been associated to the Betagalactosidase enzyme activity, and to the reduction of the chelate and sodium carbonate pectin fractions. Access 16 had high conservation, keeping flesh firmness until 32 days, with high pectin levels due to low pectinase levels. The access 2 fruits showed a high decrease on flesh firmness, what deteriorated the inner appearance of the fruit. Both pectinases activities as pectin dissolution contributed to the occurred / A firmeza da polpa tem estreita relação com a manutenção da estrutura da parede celular, dessa forma, um maior conhecimento sobre o metabolismo da parede celular é indispensável para análise de aspectos relativos à alterações na textura da polpa. No caso do melão, o estudo da firmeza da polpa é facilitado, uma vez que este apresenta uma elevada variabilidade, cuja amplitude permite observar melhor as diferenças entre fenômenos bioquímicos na parede celular. Portanto, o presente trabalho teve como objetivo avaliar o comportamento das variedades acidulus (acesso 16), momordica (acesso 2), inodorus (cv. Iracema) e cantalupensis (cv. Olympic), com relação à maturação e armazenamento dos frutos. Para tanto, dois experimentos foram instalados. No primeiro, foram estudadas as transformações que ocorrem durante a maturação dos melões, onde os frutos foram colhidos em 5 estádios de maturação, que foram pré-determinados pela antese floral; tendo utilizado o delineamento inteiramente casualizado. No segundo, os melões das variedades acidulus, momordica e inodorus foram armazenados em ambiente refrigerado (9±1 °C e 85±5% de umidade relativa), por até 32 dias e avaliados em períodos determinados para cada variedade, de modo a constituir um delineamento inteiramente casualizado para cada tipo de melão. Em ambos os experimentos os frutos foram avaliados quanto às características físicas e químicas, à atividade das pectinametilesterase, poligalacturonase e betagalactosidase, e conteúdo de pectinas em três níveis de solubilização: solúveis em água, em quelato e carbonato de sódio. O ponto de colheita ideal para os melões foram de 35 dias após a antese para cv. Iracema, 30 dias para cv. Olympic, 30 dias para o acesso 16, e 20 dias para o acesso 2. Durante a maturação foi observada elevada firmeza da polpa do acesso 16, em relação aos demais frutos avaliados, que foi associada à uma baixa atividade da betagalactosidase, bem como a manutenção de elevadas concentrações de pectinas solúveis em quelato e carbonato de sódio. O acesso 2 apresentou uma elevada queda na firmeza, com rompimento do tecido do fruto ao final da maturação; tal acontecimento foi acompanhado da elevação da concentração de pectina solúvel em água e redução das concentrações de pectinas solúveis em quelato e carbonato de sódio, em conjunto com uma elevação da atividade das pectinases ao final da maturação. O acesso 16 e o melão amarelo (cv. Iracema) possuem potencial de armazenamento de 30 dias, em condições refrigeradas. O acesso 2, nas mesmas condições, teve vida útil pós-colheita de 10 dias. A perda da firmeza dos melões estudados está associada à atividade da enzima Beta-gal, e à redução das frações de pectina, solúveis em quelato e carbonato. O acesso 16 teve elevada vida útil, com manutenção da firmeza da polpa até 32 dias, mantendo elevados níveis de pectina, solúveis em quelato e carbonato de sódio, devido à baixa atividade das pectinases. Os frutos do acesso 2 apresentaram uma queda elevada na firmeza da polpa, fato que deteriorou a aparência interna do fruto. Tanto a atividade das pectinases quanto a dissolução das pectinas contribuíram para o ocorrido / 2017-07-03
20

Evaluation of anticancer activity of momordica balsamina extracts and potential interactions with a conventional anticancer drug in colon cancer

Malemela, Kholofelo Mmanoko January 2021 (has links)
Thesis (Ph.D. (Biochemistry)) -- University of Limpopo, 2021 / Cancer remains one of the leading causes of morbidity and mortality worldwide with an estimated 9.9 million deaths in 2020. Cancer treatment regimens such as chemotherapy and radiotherapy have over the years fallen short due to drug resistance, toxicity, damage to normal healthy cells and tissues surrounding the treatment area. Moreover, they have shown very limited survival benefits for most advanced staged cancers such as colorectal cancer, which in 2020 was responsible for 3 728 deaths with a 6.8% incidence rate. Despite the many efforts in developing alternative chemotherapeutic strategies, cancer of the colon and cancer, in general, remains a burden. For centuries, plants and plant derivatives have been exploited for their nutritional and medicinal properties and now serve as chemical scaffolds or templates for designing and synthesising products with pharmacological importance. Herbal medicines are claimed to enhance therapeutic effects and are often used in combination with chronic medication. However, the concurrent use of herbal medicines and synthetic drugs may affect the pharmacokinetic profile of therapeutic drugs or trigger unexpected and undesirable effects. This study aimed to characterise the leaf extracts (crude water and crude methanol) of Momordica balsamina and investigate their potential anticancer activity on HT-29 colon cancer cells. The study also aimed to asses the effect of the extracts on drug metabolising enzymes (CYP450), specifically those which metabolise 5-Fluorouracil (5-FU) prodrugs or are inhibited by 5-FU since it is one of the first-line treatments for colon cancer. Dried powdered leaves were extracted using water and absolute methanol to obtain crude water and crude methanol extracts, respectively. For characterisation, the extracts were spotted on thin-layer chromatography (TLC) plates and further screened using chemical tests. The ferric ion reducing power assay and Liquid chromatographymass spectrometry were used to determine the antioxidant activity of the extracts and to identify prominent or abundant compounds in each extract, respectively. To assess the cytotoxic effect of the extracts and 5-FU, HT-29 colon cancer cells and C2C12 muscle cells, which were used as a model for normal cells, were exposed to concentrations that ranged from 0 to 2000 µg/ml for the water (H2O) extract, 0 to 300 µg/ml for the methanol (MeOH) extract or 0 to 100 µg/ml of 5-FU for 24 and 72 hours, and subjected to the MTT assay. The effect of the extracts on the efficacy of 5-FU was xxi assessed using the MTT assay by combined treatments of the extract and 5-FU. Genotoxicity of the extracts was assessed on the C2C12 cells using the Muse™ MultiColour DNA Damage kit. The generation of intracellular reactive oxygen species (ROS) was assessed by flow cytometry using the DCFH-DA assay. The JC-1 and acridine orange (AO)/propidium iodide (PI) staining assays were used to assess the effect of the extracts on the mitochondrial potential as well as cell and nuclear morphology, respectively. Apoptosis was quantified by flow cytometry using annexin V/PI and caspase activation assessed using the Caspase-8 and Caspase-9 colourimetric assay kits. The pro-apoptotic mechanism(s) was determined by assessing the expression profiles of selected apoptosis regulatory proteins using the human apoptosis antibody array kit. Cell cycle analysis by flow cytometry was conducted to determine the effect of the extract on the cell division cycle. Moreover, to determine the potential of herb-drug interactions, the Vivid® CYP450 Screening kits and P-gp-GloTM Assay Systems with P-glycoprotein were used to assess the effect on the activity of drug metabolising enzymes and drug transportation, respectively. The results showed that the MeOH extract possessed fewer polar compounds, higher ferric iron-reducing power, and a relative abundance of flavonol glycosides, cucurbitane-type triterpenoid aglycones, and cucurbitane-type glycosides than the H2O extract. The MeOH extract was further selectively cytotoxic to the HT-29 colon cancer cells at 24 hours of treatment and selectively induced genotoxicity in HT-29 cells. The H2O extract, however, was not cytotoxic to the HT-29 cells at all the tested concentrations at 24 and 72 hours of treatment. Analysis of nuclear and cell morphology suggested that the decrease in the percentage viability of MeOH extracttreated cells was associated with apoptotic cell death. Apoptosis was further confirmed by the loss of mitochondrial potential, increase in ROS production, caspase-8 and -9 activities as well as Annexin-V/PI-stained cells. Cell cycle analysis revealed cell cycle arrest at the S phase in MeOH extract-treated cells. Analysis of protein expression profiles revealed that the extract modulated various proteins that play a role in the promotion or inhibition of apoptosis. Moreover, the MeOH extract was shown to inhibit the activity of CYPs 1A2, 2A6, 2C8, and 2C9, while the H2O extract showed no significant inhibitory effects on the activity of all tested CYPs and 5-FU only significantly inhibited the activity of CYP2C9. However, combinatory treatments with 5-FU and the MeOH extract were shown to have no additive or diminishing effects on the efficacy of 5-FU on the activity of all the tested CYP enzymes. Treatment with 5FU (0.008 – 32 μg/ml) and the H2O extract (0.02 – 200 μg/ml) was shown to stimulate the ATPase activity of P-gp, while the MeOH extract significantly inhibited its activity with concentrations of 0.2, 2, and 20 μg/ml. In conclusion, the MeOH extract selectively induced cancer cell toxicity, genotoxicity as well as S phase cell cycle arrest and apoptosis via the intrinsic and extrinsic pathways. The anticancer activity of the MeOH leaf extract of M. balsamina as well as its antioxidant potential may be attributed to the presence and relative abundance of flavonol glycosides, cucurbitane-type triterpenoid aglycones, and cucurbitane-type glycosides. Although the MeOH extract may potentially reverse the effects of P-gp multidrug resistance by decreasing its activity, its inhibition of the activity of CYPs 1A2, 2A6, 2C8 and, 2C9, which are involved in the metabolism of more than 80% of the drugs in clinical use may suggest that co-administration of the MeOH extract may still result in increased plasma levels of drugs, thereby resulting in toxicity. The H2O extract, although not pro-apoptotic as the MeOH extract may still have the potential to be developed as a nutraceutical as it was shown to exhibit no adverse drug interactions and because this species is known to possess a wide variety of nutritional and medicinal values. / South African Medical Research Council (SAMRC) Research Capacity Development Initiative.

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