RESUMO
Feroxyhite (δ-FeOOH) nanomaterials were successfully synthesized through the atmospheric AC microplasma method at room temperature from ferrous sulfate aqueous solutions. Various syntheses conditions, including electric voltage, electric field strength, ferrous concentration, hydrogen peroxide concentration, and reaction duration, were systematically investigated. The synthesized products were characterized through x-ray diffraction, UV-vis absorption spectroscopy, photoluminescence spectroscopy, infra-red spectroscopy, and electron microscopy. The bandgap of the produced materials were strongly dependent of the ferrous concentration while the product ratio was dependent on all experimental conditions. The synthesis mechanism was thoroughly discussed. The synthesized nanomaterials were amorphous nanospheres, showing superparamagnetic properties at room temperature. The synthesized oxyhydroxide is a potential photovoltaic material besides its reported applications in photocatalysts and supercapacitors. The application of this synthesis technique could be extended to synthesize other oxy-hydroxide nanomaterials for renewable energy applications facilely, scalablely, cost-effectively, and environmentally.
RESUMO
Deregulation of cyclin-dependent kinase 2 (CDK2) and its activating partners, cyclins A and E, is associated with the pathogenesis of a myriad of human cancers and with resistance to anticancer drugs including CDK4/6 inhibitors. Thus, CDK2 has become an attractive target for the development of new anticancer therapies and for the amelioration of the resistance to CDK4/6 inhibitors. Bioisosteric replacement of the thiazole moiety of CDKI-73, a clinically trialled CDK inhibitor, by a pyrazole group afforded 9 and 19 that displayed potent CDK2-cyclin E inhibition (Ki = 0.023 and 0.001 µM, respectively) with submicromolar antiproliferative activity against a panel of cancer cell lines (GI50 = 0.025-0.780 µM). Mechanistic studies on 19 with HCT-116 colorectal cancer cells revealed that the compound reduced the phosphorylation of retinoblastoma at Ser807/811, arrested the cells at the G2/M phase, and induced apoptosis. These results highlight the potential of the 2-anilino-4-(1-methyl-1H-pyrazol-4-yl)pyrimidine series in developing potent and selective CDK2 inhibitors to combat cancer.
Assuntos
Antineoplásicos , Neoplasias , Humanos , Quinase 2 Dependente de Ciclina , Quinases Ciclina-Dependentes/metabolismo , Antineoplásicos/farmacologia , Pirimidinas/farmacologia , Pirazóis/farmacologiaRESUMO
BACKGROUND: The patients' perception of the health service is a vital tool for measuring health service quality. Besides, Patient satisfaction is an essential feature in assessing the quality of health services. Health institution leaders are considering quantifiable patient satisfaction data as a means to evaluate the health care service. METHOD: An institution-based cross-sectional study was employed from 21/8/2022 to 21/9/2022 among 308 patients attending ART pharmacy services in three health institutions of Dembia distinct. Data were collected by using a questionnaire and reviewing medical charts. Results were calculated and presented in the form of texts, tables, and graphs. Variables with a p-value of 0.05 were considered significant determinants of patient satisfaction. RESULT: A total of 308 HIV patients were recruited with a response rate of 100%. The overall prevalence of satisfaction among respondents was 231(75%). Being unable to read and write [1.21(AOR = 1.07-4.31)] and patient age greater than 48 years 1.9(0.73-2.59) were significantly associated with the level of patient satisfaction. Among the participants 66.9% were satisfied with clear and organized service, and 76% were satisfied with the convenience of a private counseling room. CONCLUSION: The general patient satisfaction at the antiretroviral therapy clinic did not achieve the national target of 85% satisfaction with significant differences among health centers. Being educated to a higher level, absence of signs and directions to ART clinics, and not having the opportunity to ask questions were the factors influencing patient satisfaction with ART service.
Assuntos
Infecções por HIV , Humanos , Pessoa de Meia-Idade , Infecções por HIV/tratamento farmacológico , Satisfação do Paciente , Etiópia , Estudos Transversais , Farmacêuticos , Inquéritos e Questionários , Instituições de Assistência AmbulatorialRESUMO
A new rhodamine 6G derivative R1 has been synthesized by condensation of rhodamine hydrazide and 6-hydroxymethyl-pyridine using microwave-assisted reaction. Naked-eye colorimetric and photo physical studies show the synthesized compound is selectively sensing Cu2+ in CH3CN/H2O (9:1, v/v) solution. Upon coordination with Cu2+ ion, the spirolactam of R1 is opened, which results in a formation of highly fluorescent complex and change in color of the solution. The Job's plot indicates 1:2 binding stoichiometry between Cu2+ ion and R1. Limit of detection for Cu2+ was determined to be 1.23 µM. The sensor was successfully applied to fluorescent imaging of Cu2+ ion in living cells.
RESUMO
BACKGROUND: Kniphofia foliosa is a flamboyant robust perennial herb which has dense clumps and tick upright rhizomes with leaves at the base. In Ethiopia, it has several vernacular names including Abelbila, Ashenda, Amelmela, Yeznjero Ageda, Shemetmetie and Yezinjero Ageda. The plant is endemic to Ethiopian highlands, where its rhizomes are traditionally used for the treatment of malaria, abdominal cramps and wound healing. In the present study, the 80% methanol extract of K. foliosa rhizomes and its constituents are tested against Plasmodium berghei in mice. METHODS: Isolation was carried out using column and preparative thin layer chromatography (PTLC). The chemical structures of the compounds were elucidated by spectroscopic methods (ESI-MS, 1D and 2D-NMR). Peters' 4-day suppressive test against P. berghei in mice was utilized for in vivo anti-malarial evaluation of the test substances. RESULTS: Two compounds, namely knipholone and dianellin were isolated from the 80% methanolic extract of K. foliosa rhizomes, and characterized. The hydroalcoholic extract (400 mg/kg) and knipholone (200 mg/kg) showed the highest activity with chemosuppression values of 61.52 and 60.16%, respectively. From the dose-response plot, the median effective (ED50) doses of knipholone and dianellin were determined to be 81.25 and 92.31 mg/kg, respectively. Molecular docking study revealed that knipholone had a strong binding affinity to Plasmodium falciparum l-lactate dehydrogenase (pfLDH) target. CONCLUSION: Results of the current study support the traditional use of the plant for the treatment of malaria.
Assuntos
Antimaláricos/farmacologia , Asphodelaceae/química , Extratos Vegetais/farmacologia , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Animais , Antraquinonas/química , Antraquinonas/farmacologia , Antimaláricos/química , Feminino , Masculino , Camundongos , Extratos Vegetais/química , Rizoma/química , Testes de Toxicidade AgudaRESUMO
INTRODUCTION: Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are involved in the initiation and progression of various cancers. Deregulation of the CDK4/6-cyclin D-retinoblastoma (Rb) pathway is common in ovarian cancer and is associated with an aggressive phenotype and poor prognosis. Patients with advanced ovarian cancer whose tumor demonstrates Rb-positivity, a low expression of p16 and overexpression of cyclin D1 are most likely to benefit from CDK4/6 inhibition. MATERIALS AND METHOD: Anti-proliferative activity and mechanistic investigations for CDDD2-94, employing palbociclib as comparator, were evaluated by MTT assay, cell cycle and apoptosis analysis, western blotting as well as senescence and colony formation assay. In vivo safety and efficacy studies were done in A2780 tumor-bearing nude mice. Combinations of CDDD2-94 with mTOR, MEK, PI3K or PARP inhibitors were evaluated in A2780 and OVCAR5 ovarian cancer cells. RESULTS: Consistent with a CDK4-targeted mechanism, CDDD2-94 arrested the G1/G0 cell cycle, induced senescence and inhibited the proliferation of Rb-proficient ovarian cancer cells. CDDD2-94 exhibited synergistic anti-proliferative activities with mTOR, MEK, PI3K or PARP inhibitors. Importantly, unlike palbociclib which caused significant reductions in the number of lymphocytes and neutrophils, CDDD2-94 had little effect. CDDD2-94, as single agent and in combination with everolimus, delayed tumor growth and significantly increased survival of mice. CONCLUSION: Given its high specificity in targeting CDK4 and excellent anti-tumor efficacy with low toxicity, CDDD2-94 has potential to be developed as a standalone agent or in combination with targeted therapeutics for the treatment of ovarian cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Neoplasias Ovarianas/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Everolimo/farmacologia , Everolimo/uso terapêutico , Feminino , Humanos , Camundongos , Neoplasias Ovarianas/patologia , Ovário/patologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Two new chemosensors, rhodamine B derivative bearing 3-formyl-6-nitrochromone (L 1 ) and 3-formyl-6-methylchromone (L 2 ) units were designed and synthesized using microwave irradiation for the selective detection of Cu2+ in aqueous media. Copper triggers the formation of highly fluorescent ring-open spirolactam. The fluorescence intensity was remarkably increased upon the addition of Cu2+ within a minute, while the other metal ions caused no significant effect. More importantly, the resulting complexes can be used as a reversible fluorescence sensor for CN-. The recognition ability of the sensors was investigated by fluorescence titration, Job's plot, 1H NMR spectroscopy and density functional theory (DFT) calculations.
RESUMO
Post-translational modulation of eIF4E through phosphorylation by Mnks is highly integral to the pathogenesis of different cancers. Therefore, inhibition of Mnks offers a strategy for cancer treatment. Herein, a series of 2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione derivatives is presented as Mnk inhibitors. Some of them showed sub-micromolar to low nanomolar inhibitory activities against Mnk1/2 with a high level of selectivity for both kinases over CDKs. Biochemical assays revealed that compounds 4c and 4t are non-ATP-competitive inhibitors of Mnks. Lead compound 4t demonstrated a high selectivity for Mnk1/2 over a selection of 51 kinases, and displayed anti-proliferative activities against a panel of cancer cell lines. However, this compound in combination with our in-house CDK4/6 inhibitor 83 did not show a synergistic effect in A2780 ovarian cancer cells, suggesting that caution be exercised in the selection of an agent to be combined with an Mnk inhibitor.
Assuntos
Antineoplásicos/farmacologia , Cicloexanos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Compostos de Espiro/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cicloexanos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Piridinas/química , Compostos de Espiro/química , Relação Estrutura-AtividadeRESUMO
Unsafe drinking water is a recognized health threat in Ethiopia, and climate change, rapid population growth, urbanization and agricultural practices put intense pressure on availability and quality of water. Climate change-related health problems due to floods and waterborne diseases are increasing. With increasing insight into impacts of climate change and urbanization on water availability and quality and of required adaptations, a shift towards climate-resilient water safety planning was introduced into an Ethiopian strategy and guidance document to guarantee safe drinking water. Climate-resilient water safety planning was implemented in the urban water supplies of Addis Ababa and Adama, providing drinking water to 5 million and 500,000 people, respectively. Based on the risks identified with climate-resilient water safety planning, water quality monitoring can be optimized by prioritizing parameters and events which pose a higher risk for contaminating the drinking water. Water quality monitoring was improved at both drinking water utilities and at the Public Health Institute to provide relevant data used as input for climate-resilient water safety planning. By continuously linking water quality monitoring and climate-resilient water safety planning, utilization of information was optimized, and both approaches benefit from linking these activities.
Assuntos
Mudança Climática , Água Potável , Qualidade da Água , Abastecimento de Água/normas , Etiópia , Humanos , Medição de Risco , Gestão de RiscosRESUMO
Cisplatin and other metal-based drugs often display side effects and tumor resistance after prolonged use. Because rhenium-based anticancer complexes are often less toxic, a novel series of organorhenium complexes were synthesized of the types: XRe(CO)3Z (X = α-diimines and Z = p-toluenesulfonate, 1-naphthalenesulfonate, 2-naphthalenesulfonate, picolinate, nicotinate, aspirinate, naproxenate, flufenamate, ibuprofenate, mefenamate, tolfenamate, N-acetyl-tryptophanate), and their biological properties were examined. Specifically, in hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells, the p-toluenesulfonato, 1-naphthalenesulfonato, 2-naphthalenesulfonato, picolinato, nicotinato, acetylsalicylato, flufenamato, ibuprofenato, mefenamato, and N-acetyl-tryptophanato complexes were found to be far more potent than conventional drug cisplatin. DNA-binding studies were performed in each case via UV-Vis titrations, cyclic voltammetry, gel electrophoresis, and viscosity, which suggest DNA partial intercalation interaction, and the structure-activity relationship studies suggest that the anticancer activities increase with the increasing lipophilicities of the compounds, roughly consistent with their DNA-binding activities.
Assuntos
Antineoplásicos , Complexos de Coordenação , Compostos Organometálicos , Rênio , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Feminino , Humanos , Células MCF-7 , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Rênio/química , Rênio/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND: In Ethiopia, the leaves of Syzygium guineense have been found useful for the prevention and cure of malaria, and demonstrated antiplasmodial activity in vitro. Nevertheless, no scientific study has been conducted to confirm its antimalarial activity in vivo. Therefore, the objective of the study was to evaluate the antimalarial effect of Syzygium guineense leaf extract in mice. METHODS: Inoculation of the study mice was carried out by using the malaria parasite, Plasmodium berghei. The plant extract was prepared at 200, 400 and 600 mg/kg. Chloroquine and distilled water was administered to the positive and negative control groups respectively. Parameters like parasitaemia, survival time and body weight were determined following standard tests (4-day suppressive, Rane's and repository tests). RESULTS: Syzygium guineense crude leaf extract displayed considerable (p < 0.05) parasite suppression at doses of 600 and 400 mg/kg in a 4-day suppressive test with chemosuppressive value of 59.39 and 49.09% respectively. S. guineense crude leaf extract also showed dose-dependent schizontocidal activity in both the repository and curative tests. The extract also prevented body weight loss and prolonged survival date of mice significantly (P < 0.05) at the highest dose employed in the study. Qualitative chemical assay for S. guineense methanolic leaf extract revealed that the plant is endowed with different plant secondary metabolites exemplified by terpenoids, alkaloids, triterpenes, flavonoids, anthraquinones, tannins, glycosides, saponins and phenols. CONCLUSION: Syzygium guineense leaf extract possess antimalarial activity in mice. The test substance was found to be safe with no observable signs of toxicity in the study mice. The results of the present work confirmed the in vitro antiplasmodial finding and traditional claims in vivo in mice. Therefore, Syzygium guineense could be regarded as a potential source to develop safe, effective and affordable antimalarial agent.
Assuntos
Antimaláricos/administração & dosagem , Malária/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Plasmodium berghei/efeitos dos fármacos , Syzygium/química , Animais , Feminino , Humanos , Masculino , Camundongos , Folhas de Planta/química , Plasmodium berghei/fisiologiaRESUMO
An amino acid based and bidentate Schiff base, (E)-methyl 2-((2-oxonaphthalen-1(2H)-ylidene)methylamino)acetate (ligand), was synthesized from the reaction of glycine-methyl ester hydrochloride with 2-hydroxy-1-naphthaldehyde. Characterization of the ligand was carried out using theoretical quantum-mechanical calculations and experimental spectroscopic methods. The molecular structure of the compound was confirmed using X-ray single-crystal data, NMR, FTIR and UV-Visible spectroscopy, which were in good agreement with the structure predicted by the theoretical calculations using density functional theory (DFT). Antimicrobial activity of the ligand was investigated for its minimum inhibitory concentration (MIC) to several bacteria and yeast cultures. UV-Visible spectroscopy studies also shown that the ligand can bind calf thymus DNA (CT-DNA) electrostatic binding. In addition, DNA cleavage study showed that the ligand cleaved DNA without the need for external agents. Energetically most favorable docked structures were obtained from the rigid molecular docking of the compound with DNA. The compound binds at the active site of the DNA proteins by weak non-covalent interactions. The colorimetric response of the ligand in DMSO to the addition of equivalent amount of anions (F-, Br-, I-, CN-, SCN-, ClO4-, HSO4-, AcO-, H2PO4-, N3- and OH-) was investigated and the ligand was shown to be sensitive to CN- anion.
Assuntos
Acetatos/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Cianetos/análise , Naftalenos/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Acetatos/síntese química , Acetatos/química , Animais , Ânions/análise , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Bovinos , DNA/efeitos dos fármacos , Clivagem do DNA , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Naftalenos/síntese química , Naftalenos/química , Teoria Quântica , Eletricidade Estática , Relação Estrutura-AtividadeRESUMO
The application of IR 786 perchlorate (IR-786) as a selective optical sensor for cyanide anion in both organic solution (acetonitrile (MeCN), 100%) and solvent-free solid surfaces was demonstrated. In MeCN, IR-786 was selective to two anions in the following order: CN(-) > OH(-). A significant change in the characteristic dark green color of IR-786 in MeCN to yellow was observed as a result of nucleophilic addition of CN(-) to the fluorophore, i.e., formation of IR 786-(CN), which was also verified by a blue shift in the 775 nm absorbance peak to 430 nm. A distinct green fluorescence emission from the IR-786-(CN) in MeCN was also observed, which demonstrated the selectivity of IR-786 towards CN(-) in MeCN. Fluorescence emission studies of IR-786 showed that the lower detection limit and the sensitivity of IR-786 for CN(-) in MeCN was 0.5 µM and 0.5 to 8 µM, respectively. The potential use of IR-786 as a solvent-free solid state sensor for the selective sensing and monitoring of CN(-) in the environment was also demonstrated. On solvent-free solid state surfaces, the sensitivity of the IR-786 to CN(-) in water samples was in the range of 50-300 µM with minimal interference by OH(-).
Assuntos
Ânions/isolamento & purificação , Cianetos/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Água/química , Carbocianinas/química , Cianetos/química , Corantes Fluorescentes/química , Humanos , Indóis/química , Solventes/química , Espectrometria de Fluorescência , Poluentes Químicos da Água/químicaRESUMO
Ranunculin, a glucoside, serves as a chemotaxonomic marker in Ranunculaceae plants. When these plants are damaged, an enzyme ß-glucosidase triggers the conversion of ranunculin into protoanemonin through hydrolysis. Subsequently, protoanemonin undergoes cyclodimerization to form anemonin. The inherent instability of ranunculin and the rapid dimerization of protoanemonin render them unsuitable for use in biological assays. Conversely, anemonin stands out as the optimal molecule for bioassays and demonstrates diverse biological properties, including anti-inflammatory, anti-infective, and anti-oxidant effects. Among these, anemonin exhibits the greatest promise in addressing conditions such as arthritis, cerebral ischemia, and ulcerative colitis. Its potential medical uses are enhanced by its capacity to inhibit nitric oxide synthesis and successfully counteract lipopolysaccharide-induced inflammation. This review describes the chemistry and biological properties of anemonin and its precursors, including discussions on extraction, isolation, synthesis, and investigations into bioactivity and pharmacokinetics.
RESUMO
Subcritical water (SCW) hydrolysis was applied to valorize the low-valued ray-finned fish (Labeobarbus nedgia) into valuable protein hydrolysates, employing N2 and CO2 as pressurization agents at varying temperatures (140, 160, 180, and 200 °C). The degree of hydrolysis (DH) and total free amino acid content increased with temperature for both pressurizing agents. The highest DH (54.5 ± 0.4%) and total free amino acid content (210 ± 1 mg/gprot) were observed at 200 °C when CO2 gas was used as the pressurizing agent. Predominantly, glycine and alanine were released for both pressurizing agents. The antioxidant activity, evaluated through three different assays, increased with temperature and was found to be the highest at 200 °C. This study illustrated the advantages of the intensified SCW technology by using CO2 as a pressurization agent in valorizing low-valued ray-finned fish (Labeobarbus nedgia), as animal residue rich in proteins, for the production of valuable protein hydrolysates with a high fraction of valuable free amino acids, which could offer potential applications as a functional ingredient in the food industry.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Psydrax schimperianus (A. Rich.) Bridson. roots are used for the treatment of diarrhea in West Arsi zone, Ethiopia. AIM OF THE STUDY: This study aimed to investigate the in vivo antidiarrheal activity of crude extract and coumarins isolated from the roots of Psydrax schimperianus to provide a pharmacological basis for its traditional use as an antidiarrheal agent in Ethiopia. MATERIALS AND METHODS: The crude root extract of P. schimperianus was tested in vivo for antidiarrheal efficacy in mice utilizing castor oil-induced diarrhea, gastrointestinal transit time, and enteropooling models at doses of 100, 200, and 400 mg/kg. Phytochemical investigation of the crude root extract led to the isolation of two coumarins, isoscopoletin, and scoparone. Isoscopoletin and scoparone were evaluated for antidiarrheal activity against castor oil-induced diarrhea model at 10 mg/kg and 20 mg/kg doses. RESULTS: The crude root extract of P. schimperianus, at doses of 100, 200, and 400 mg/kg, inhibited defecation by 37.5%, 46.2%, and 61.2%, respectively. At a dose of 20 mg/kg, scoparone and isoscopoletin reduced defecation by 61.2% and 66.6%, respectively. CONCLUSION: The study warrants further investigation of isoscopoletin and scoparone towards development as a novel treatment for diarrheal diseases.
Assuntos
Antidiarreicos , Óleo de Rícino , Camundongos , Animais , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Extratos Vegetais/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Cumarínicos/farmacologia , Cumarínicos/uso terapêuticoRESUMO
Background: In Ethiopian traditional medicine, V. sinaiticum is one of the most often utilized medicinal herbs for the treatment of diarrhea. Therefore, this study was conducted to validate the use of the plant for the treatment of diarrhea in the traditional medical practice of Ethiopia. Methods: Castor oil-induced diarrhea, enteropooling, and intestinal motility test models in mice were used to evaluate the antidiarrheal properties of the 80% methanol crude extract and the solvent fractions of the root component of V. sinaiticum. The effects of the crude extract and the fractions on time for onset, frequency, weight, and water content of diarrheal feces, intestinal fluid accumulation, and intestinal transit of charcoal meal were evaluated and compared with the corresponding results in the negative control. Results: The crude extract (CE), aqueous fraction (AQF), and ethyl acetate fraction (EAF) at 400 mg/kg (p < 0.001) significantly delayed the onset of diarrhea. Besides, the CE and AQF at 200 and 400 mg/kg (p < 0.001) of the doses, and EAF at 200 (p < 0.01) and 400 mg/kg (p < 0.001) significantly decreased the frequency of diarrheal stools. Furthermore, CE, AQF, and EAF at their three serial doses (p < 0.001), significantly reduced the weights of the fresh diarrheal stools as compared to the negative control. The CE and AQF at 100 (p < 0.01), and 200 and 400 mg/kg (p < 0.001) of their doses and EAF at 200 (p < 0.01) and 400 mg/kg (p < 0.001) significantly decreased the fluid contents of diarrheal stools compared to the negative control. In the enteropooling test, the CE at 100 (p < 0.05), and 200 and 400 mg/kg (p < 0.001), AQF at 200 (P < 0.05) and 400 mg/kg (p < 0.01), and EAF at 200 (p < 0.01) and 400 mg/kg (p < 0.001) significantly decreased the weights of intestinal contents compared to the negative control. Additionally, the CE at 100 and 200 (p < 0.05) and 400 mg/kg (p < 0.001), AQF at 100 (p < 0.05), 200 (p < 0.01), and 400 mg/kg (p < 0.001) of the doses, and EAF at 400 mg/kg (p < 0.05), produced significant reductions in the volumes of intestinal contents. In the intestinal motility test model, the CE, AQF, and EAF at all their serial doses (p < 0.001), significantly suppressed the intestinal transit of charcoal meal and peristaltic index compared to the negative control. Conclusion: Overall, the results of this study showed that the crude extract and the solvent fractions of the root parts of V. sinaiticum had considerable in vivo antidiarrheal activities. Besides, the crude extract, especially at 400 mg/kg, produced the highest effect followed by the aqueous fraction at the same dose. This might indicate that the bioactive compounds responsible for the effects are more of hydrophilic in nature. Moreover, the antidiarrheal index values were increased with the doses of the extract and the fractions, suggesting that the treatments might have dose-dependent antidiarrheal effects. Additionally, the extract was shown to be free of observable acute toxic effects. Thus, this study corroborates the use the root parts of V. sinaiticum to treat diarrhea in the traditional settings. Furthermore, the findings of this study are encouraging and may be used as the basis to conduct further studies in the area including chemical characterization and molecular based mechanism of actions of the plant for its confirmed antidiarrheal effects.
RESUMO
Lobelia giberroa Hemsl. is an endogenous Ethiopian medicinal plant with a long history of use in the treatment of malaria, bacterial and fungal diseases, and cancer. Here, we present the in vivo bioassay-guided fractionation of the 80% methanol extract of L. giberroa roots, which led to the isolation of lobetyolin. L. giberroa roots were extracted with 80% methanol, and the dried 80% methanol extract was fractionated with hexane, ethyl acetate, methanol, and water. Acute oral toxicity study was conducted according to the Organisation for Economic Co-operation and Development Guideline 425 by using female Swiss albino mice. Antimalarial activity was assessed in Plasmodium berghei-infected Swiss albino mice. Through in vivo bioassay-guided fractionation processes lobetyolin, a C14-polyacetylene glucoside, was isolated from the methanol fraction by silica gel column chromatography as the main active ingredient from the plant. The chemical structure of lobetyolin was elucidated by interpretation of spectroscopic data (1HNMR, 13CNMR, IR. MS) including two dimensional NMR. The plant extract was considered safe for administration up to 2000 mg/kg. In the four-day suppressive test, the 80% methanol extract (400 mg/kg), methanol fraction (400 mg/kg), and lobetyolin (100 mg/kg) exhibited antimalarial activity, with chemosuppression values of 73.05, 64.37, and 68.21%, respectively. Compared to the negative control, which had a mean survival time of 7 days, the lobetyolin (100 mg/kg) and methanol fraction (400 mg/kg) treated groups had mean survival times of 18 and 19 days, respectively. The current study supports the traditional use of the plant for the treatment of malaria. The structural differences between lobetyolin and existing antimalarials, as well as its previously unknown antimalarial activity, make it of interest as an early lead compound for further chemical optimization.
Assuntos
Antimaláricos , Lobelia , Animais , Feminino , Camundongos , Extratos Vegetais/química , Plasmodium berghei , Plasmodium falciparum , Poli-InosRESUMO
In the present study, we use knipholone as a prototype molecule to identify new anti-infective agents. Since knipholone is insoluble in water, which would have a detrimental effect on its bioavailability and efficacy, we synthesized knipholone Mannich base derivatives (2-4) that have better predicted solubility and investigated their in vitro antimicrobial activity against eight pathogenic bacterial and fungal strains. The chemical structures of compounds 1-4 were elucidated from their 1H and 13C NMR data, and their antimicrobial activity evaluation was carried out by a broth microdilution MTT assay. Compound 3 exhibited the strongest efficacy against Staphylococcus epidermidis, with MIC value of 9.7 µg/mL. While 4 exhibited the best activity against Staphylococcus aureus, with an MIC value of 19.5 µg/mL, and was the only one to significantly inhibit the fungus Trichophyton mentagrophytes (MIC = 78.2 µg/mL). The study provides evidence for the antibacterial activity of aminoalkyl derivatives of knipholone.