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1.
J Ethnopharmacol ; 247: 112223, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31553926

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Arecae semen has been used as vermifuge and digestant in traditional Chinese medicine (TCM) for more than one thousand years. However, the toxicity effect of areca semen and its underlying mechanism are still unclear. THE AIM OF THE STUDY: This study was aimed to investigate the toxicity of arecae semen and to explore its mechanisms by serum metabolomics. MATERIALS AND METHODS: The male Wistar rats were divided into the control group and treated group (n = 6 in each group), which were given by gavage with distill water or arecae semen aqueous extract (ASAE) once a day for 30 days, respectively. Serum samples were collected from all the rats after treatment of 7-day, 14-day and 30-day for metabolomics analysis. Moreover, biochemistry analysis and histopathological examination were performed at the end of study. RESULTS: The phenomenon of diarrhea, less physical activity, tremors and body curl up were observed in the treated group. Additionally, the body weights of treated rats were significantly decreased compared with control rats from the 8th day after oral administration. Except the level of creatinekinase (CK) in the treated group significantly increased compared with the control group, there were no differences on biochemistry parameters and histopathological test in the two groups. Combined with the methods of principal component analysis (PCA), orthogonal projection to latent structure-discrimination analysis (OPLS-DA) and available databases, the treated and control rats were clearly distinguished from each other and 19 metabolites were identified as the potential biomarkers in the arecae semen treated rats. The identified biomarkers indicated that there were perturbations of the phospholipid metabolism, amino acid metabolism and fat acid metabolism in the treated group. CONCLUSIONS: This indicated that arecae semen possessed certain cardiotoxicity and inhibited the normal growth in Wistar male rats. In addition, the metabolomics approach is a useful tool to study the toxicity in TCM.


Assuntos
Areca/química , Cardiotoxicidade/etiologia , Medicamentos de Ervas Chinesas/toxicidade , Crescimento e Desenvolvimento/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Administração Oral , Aminoácidos/metabolismo , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/toxicidade , Biomarcadores/sangue , Biomarcadores/metabolismo , Cardiotoxicidade/sangue , Cardiotoxicidade/diagnóstico , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/isolamento & purificação , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/isolamento & purificação , Fármacos Gastrointestinais/toxicidade , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metabolômica , Ratos , Ratos Wistar , Sementes/química , Testes de Toxicidade , Água/química
2.
BMC Vet Res ; 15(1): 360, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640708

RESUMO

BACKGROUND: Paramphistomosis is a pathogenic disease of domesticated ruminants, causing great economic loss in dairy industry and meat production. It is considered as a neglected tropical disease with highest prevalence throughout tropical and subtropical regions, particularly in Africa, Asia, Europe, and Australia. There are few trematocidal drugs available in the market. Most are resistant and have elevated side effects. Therefore, alternative trematocidal drugs need to discover. This study was conducted to evaluate three plants leaf extracts (from Senna alata, S. alexandrina, and S. occidentalis) as effective remedies against gastrointestinal trematode parasite (Paramphistomum gracile) of ruminants. Live adult parasites were collected in 0.1 M phosphate-buffered saline (PBS) from fresh autopsied goat's rumen. Parasites were incubated in leaf extracts of S. alata, S. alexandrina and, S. occidentalis individually and in combination (1:1) ratio at 37 ± 1°C. Treatment media contain extracts at different concentrations (10, 20 and 40 mg/mL) in 10 mL of 0.1 M PBS with 1% dimethylsulphoxide (DMSO). Parasites in control group were incubated in PBS without extract. The efficacy of three Senna extracts was evaluated on the basis of dose-dependent motility and mortality of the trematode. Immediately after paralysis, all treated parasites were collected for histology, SEM and biochemical study. RESULTS: Dose-dependent efficacy was observed in terms of motility and time of mortality in all treated parasites after exposure in various concentrations of the Senna plant extracts. S. occidentalis and S. alexandrina showed better efficacy in combination than comparing with individual treatment groups. Histological study and scanning electron microscopic observations revealed conspicuous deformity of surface architecture in all treated parasites. Scanning electron micrographs also revealed shrinkage, vacuolization, infoldings and blebbings on the body surface of treated worms. Activities of tegumental enzymes were inhibited in all treatment groups compared to control. CONCLUSION: The overall findings from this study revealed that all three Senna leaf extracts individually and in combination showed potential antitrematocidal activity against Paramphistomum gracile by damaging body tegument and neural propagation. Thus, this study confirmed that all three Senna extracts can be considered as a potential drug-like candidate in indigenous system of traditional medicine against trematode infections in livestock.


Assuntos
Anti-Helmínticos/farmacologia , Paramphistomatidae/efeitos dos fármacos , Extratos Vegetais/farmacologia , Senna (Planta)/química , Animais , Anti-Helmínticos/isolamento & purificação , Etnofarmacologia , Cabras , Paramphistomatidae/isolamento & purificação , Paramphistomatidae/ultraestrutura , Extratos Vegetais/isolamento & purificação , Rúmen/parasitologia , Infecções por Trematódeos/tratamento farmacológico , Infecções por Trematódeos/veterinária
3.
PLoS Biol ; 17(10): e3000485, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31622335

RESUMO

Schistosomes are parasitic flatworms that infect over 200 million people, causing the neglected tropical disease, schistosomiasis. A single drug, praziquantel, is used to treat schistosome infection. Limitations in mass drug administration programs and the emergence of schistosomiasis in nontropical areas indicate the need for new strategies to prevent infection. It has been known for several decades that rotifers colonizing the schistosome's snail intermediate host produce a water-soluble factor that paralyzes cercariae, the life cycle stage infecting humans. In spite of its potential for preventing infection, the nature of this factor has remained obscure. Here, we report the purification and chemical characterization of Schistosome Paralysis Factor (SPF), a novel tetracyclic alkaloid produced by the rotifer Rotaria rotatoria. We show that this compound paralyzes schistosome cercariae and prevents infection and does so more effectively than analogous compounds. This molecule provides new directions for understanding cercariae motility and new strategies for preventing schistosome infection.


Assuntos
Alcaloides/farmacologia , Anti-Helmínticos/farmacologia , Cercárias/efeitos dos fármacos , Rotíferos/química , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose/prevenção & controle , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Cercárias/patogenicidade , Cercárias/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Fígado/efeitos dos fármacos , Fígado/parasitologia , Masculino , Camundongos , Movimento/efeitos dos fármacos , Movimento/fisiologia , Rotíferos/isolamento & purificação , Rotíferos/metabolismo , Schistosoma mansoni/crescimento & desenvolvimento , Schistosoma mansoni/patogenicidade , Esquistossomose/parasitologia , Esquistossomose/transmissão , Pele/efeitos dos fármacos , Pele/parasitologia , Caramujos/parasitologia , Solubilidade , Relação Estrutura-Atividade
4.
Molecules ; 24(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470508

RESUMO

Viola betonicifolia (Violaceae) is commonly recognized as "Banafsha" and widely distributed throughout the globe. This plant is of great interest because of its traditional, pharmacological uses. This review mainly emphases on morphology, nutritional composition, and several therapeutic uses, along with pharmacological properties of different parts of this multipurpose plant. Different vegetative parts of this plant (roots, leaves, petioles, and flowers) contained a good profile of essential micro- and macronutrients and are rich source of fat, protein, carbohydrates, and vitamin C. The plant is well known for its pharmacological properties, e.g., antioxidant, antihelminthic, antidepressant, anti-inflammatory, analgesic, and has been reported in the treatment of various neurological diseases. This plant is of high economic value. The plant has potential role in cosmetic industry. This review suggests that V. betonicifolia is a promising source of pharmaceutical agents. This plant is also of significance as ornamental plant, however further studies needed to explore its phytoconstituents and their pharmacological potential. Furthermore, clinical studies are needed to use this plant for benefits of human beings.


Assuntos
Analgésicos/química , Anti-Helmínticos/química , Anti-Inflamatórios/química , Antidepressivos/química , Antioxidantes/química , Fármacos Neuroprotetores/química , Viola/química , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antidepressivos/isolamento & purificação , Antidepressivos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Humanos , Micronutrientes/classificação , Micronutrientes/isolamento & purificação , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Nutrientes/classificação , Nutrientes/isolamento & purificação , Fitoterapia/métodos , Componentes Aéreos da Planta/anatomia & histologia , Componentes Aéreos da Planta/química , Extratos Vegetais/análise , Extratos Vegetais/química , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/química , Plantas Medicinais , Viola/anatomia & histologia
5.
Curr Top Med Chem ; 19(22): 2032-2040, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31340738

RESUMO

BACKGROUND: Phospholipases A2 (PLA2) from snake venoms have a broad potential as pharmacological tools on medicine. In this context, strongyloidiasis is a neglected parasitic disease caused by helminths of the genus Strongyloides. Currently, ivermectin is the drug of choice for treatment, however, besides its notable toxicity, therapeutic failures and cases of drug resistance have been reported. BnSP-6, from Bothorps pauloensis snake venom, is a PLA2 with depth biochemical characterization, reporting effects against tumor cells and bacteria. OBJECTIVE: The aim of this study is to demonstrate for the first time the action of the PLA2 on Strongyloides venezuelensis. METHODS: After 72 hours of treatment with BnSP-6 mortality of the infective larvae was assessed by motility assay. Cell and parasite viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, autophagic vacuoles were labeled with Monodansylcadaverine (MDC) and nuclei of apoptotic cells were labeled with Propidium Iodide (PI). Tissue degeneration of the parasite was highlighted by Transmission Electron Microscopy (TEM). RESULTS: The mortality index demonstrated that BnSP-6 abolishes the motility of the parasite. In addition, the MTT assay attested the cytotoxicity of BnSP-6 at lower concentrations when compared with ivermectin, while autophagic and apoptosis processes were confirmed. Moreover, the anthelmintic effect was demonstrated by tissue degeneration observed by TEM. Furthermore, we report that BnSP-6 showed low cytotoxicity on human intestinal cells (Caco-2). CONCLUSION: Altogether, our results shed light on the potential of BNSP-6 as an anthelmintic agent, which can lead to further investigations as a tool for pharmaceutical discoveries.


Assuntos
Anti-Helmínticos/farmacologia , Venenos de Crotalídeos/farmacologia , Fosfolipases A2/farmacologia , Venenos de Serpentes/farmacologia , Strongyloides/efeitos dos fármacos , Animais , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Bothrops , Células CACO-2 , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Venenos de Crotalídeos/química , Venenos de Crotalídeos/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Humanos , Fosfolipases A2/química , Fosfolipases A2/isolamento & purificação , Ratos , Ratos Wistar , Venenos de Serpentes/química , Venenos de Serpentes/isolamento & purificação , Strongyloides/parasitologia , Relação Estrutura-Atividade
6.
Fitoterapia ; 137: 104239, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31201886

RESUMO

In the search for bioactive natural products from the African flora, three previously undescribed compounds including one stilbene-coumarin derivative (1), one coumarin-carbinol (2) and one fatty glycoside (3) were isolated from the stem bark and leaves of Monotes kerstingii, together with sixteen known compounds (4-19). The structures of the isolated compounds were elucidated based on their NMR and MS spectroscopic data and by comparison of these data with those previously reported in the literature. Compounds 1-19 were screened for anthelmintic and antimicrobial activity. None of the compounds exhibited significant anthelmintic activity. However, compounds 4, 5, 8 and 14 displayed interesting antibacterial activity against B. subtilis at a concentration of 100 µM with respective inhibition percentages of 99, 79, 71 and 100%, respectively, compared to erythromycin used as positive control. In addition, at the same concentration, compound 6 showed remarkable antifungal activity against Septoria tritici with 93.6% growth inhibition and was found to be more active than the positive controls epoconazole and terbinafine displaying 76.6 and 84.3%, respectively .


Assuntos
Anti-Helmínticos/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Dipterocarpaceae/química , Anti-Helmínticos/isolamento & purificação , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Camarões , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Folhas de Planta/química
7.
Vet Parasitol ; 270: 13-19, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31213236

RESUMO

Small ruminants browsing in tropical forests readily consume the foliage of Senegalia gaumeri. A S. gaumeri methanol:water extract was recently shown to have ovicidal activity against Haemonchus contortus eggs in vitro. In the present study, the fraction of a S. gaumeri methanol:water extract with ovicidal activity against H. contortus eggs and the metabolites potentially involved in this activity were identified. Bio-guided fractionation of the S. gaumeri methanol:water extract identified high ovicidal activity (80.29%, EC50 = 58.9 µg/mL) in the non-polar sub-fraction P1. Gas chromatography-mass spectrometry (GC-MS) identified several fatty acids: pentacosane (18.05%), heneicosane (18.05%), triacontane (30.94%), octacosane (18.05%), and hexanedioic acid bis-(2-ethylhexyl) ester (32.72%). Purification of the polar components of sub-fraction P1 led to the identification of p-coumaric acid as a major constituent. In egg hatch tests, 400 µg/mL p-coumaric acid resulted in an ovicidal effect of 8.7%, a larvae failing eclosion effect of 2.9%, and of the emerged larvae (88.4%), many were damaged. In conclusion, the low AH activity of p-coumaric acid against H. contortus eggs indicates that it is not solely responsible for the ovicidal activity of sub-fraction P1 but might act in synergy with other compounds in this fraction. However, p-coumaric acid showed potential anthelmintic effects against the larval stage of H. contortus.


Assuntos
Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Fracionamento Químico/métodos , Fabaceae/química , Haemonchus/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Animais , Larva/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Folhas de Planta/química
8.
Molecules ; 24(9)2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31060200

RESUMO

Leea asiatica (L.) Ridsdale (Leeaceae) is found in tropical and subtropical countries and has historically been used as a traditional medicine in local healthcare systems. Although L. asiatica extracts have been found to possess anthelmintic and antioxidant-related nephroprotective and hepatoprotective effects, little attention has been paid toward the investigation of phytochemical constituents of this plant. In the current study, phytochemical analysis of isolates from L. asiatica led to the identification of 24 compounds, including a novel phenolic glucoside, seven triterpenoids, eight flavonoids, two phenolic glycosides, four diglycosidic compounds, and two miscellaneous compounds. The phytochemical structures of the isolates from L. asiatica were elucidated using spectroscopic analyses including 1D- and 2D-NMR and ESI-Q-TOF-MS. The presence of triterpenoids and flavonoids supports the evidence for anthelmintic and antioxidative effects of L. asiatica.


Assuntos
Compostos Fitoquímicos/análise , Vitaceae/química , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Medicina Tradicional , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
9.
Molecules ; 24(7)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965575

RESUMO

Ophiorrhiza rugosa var. prostrata is one of the most frequently used ethnomedicinal plants by the indigenous communities of Bangladesh. This study was designed to investigate the antidiarrheal, anti-inflammatory, anthelmintic and antibacterial activities of the ethanol extract of O. rugosa leaves (EEOR). The leaves were extracted with ethanol and subjected to in vivo antidiarrheal screening using the castor oil-induced diarrhea, enteropooling, and gastrointestinal transit models. Anti-inflammatory efficacy was evaluated using the histamine-induced paw edema test. In parallel, in vitro anthelmintic and antibacterial activities were evaluated using the aquatic worm and disc diffusion assays respectively. In all three diarrheal models, EEOR (100, 200 and 400 mg/kg) showed obvious inhibition of diarrheal stool frequency, reduction of the volume and weight of the intestinal contents, and significant inhibition of intestinal motility. Also, EEOR manifested dose-dependent anti-inflammatory activity. Anthelmintic action was deemed significant (P < 0.001) with respect to the onset of paralysis and helminth death. EEOR also resulted in strong zones of inhibition when tested against both Gram-positive and Gram-negative bacteria. GC-MS analysis identified 30 compounds within EEOR, and of these, 13 compounds documented as bioactive showed good binding affinities to M3 muscarinic acetylcholine, 5-HT3, tubulin and GlcN-6-P synthase protein targets in molecular docking experiments. Additionally, ADME/T and PASS analyses revealed their drug-likeness, likely safety upon consumption and possible pharmacological activities. In conclusion, our findings scientifically support the ethnomedicinal use and value of this plant, which may provide a potential source for future development of medicines.


Assuntos
Diarreia/tratamento farmacológico , Inflamação/tratamento farmacológico , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/química , Rubiaceae/química , Animais , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Simulação por Computador , Diarreia/induzido quimicamente , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Inflamação/induzido quimicamente , Camundongos , Viabilidade Microbiana/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia
10.
Exp Parasitol ; 200: 37-41, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30928354

RESUMO

Toxocara spp. are responsible for causing toxocariasis, a zoonotic disease of global importance, which is difficult to treat as the available drugs have moderate efficacy in the clinical resolution of the disease. A promising alternative to the existing drugs is Propolis, which is known for having biological and pharmacological properties such as antiparasitic, antioxidant, and antitumor activities. In this study, we report the in vitro anthelmintic activity of essential oil from Brazilian Red Propolis (EOP) against larvae of Toxocara cati. Approximately 100 larvae per well were cultivated in microplates containing RPMI-1640 medium and incubated in the presence of EOP (18.75, 37.5, 75, 150, 300 and 600 µg/mL) to determine the Minimum Inhibitory Concentration (MIC) and IC50 (concentration required to inhibit 50% of the population) values. Then, T. cati larvae treated with the MIC of EOP were inoculated in mice to evaluate their progression in vivo. A concentration of 600 µg/mL of EOP showed 100% larvicidal activity after exposure for 48 h, while 300 µg/mL represented the IC50 and CC50. The anthelmintic activity of EOP was confirmed by the inability of the treated T. cati larvae to infect the mice. Our findings demonstrate the potential of EOP as an anthelmintic.


Assuntos
Anti-Helmínticos/farmacologia , Óleos Voláteis/farmacologia , Própole/química , Toxocara/efeitos dos fármacos , Animais , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/toxicidade , Células CHO , Corantes , Cricetinae , Cricetulus , Feminino , Concentração Inibidora 50 , Cinética , Larva/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Movimento/efeitos dos fármacos , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/toxicidade , Toxocara/fisiologia , Azul Tripano
11.
PLoS Negl Trop Dis ; 13(3): e0007240, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30870428

RESUMO

Natural products have moved into the spotlight as possible sources for new drugs in the treatment of helminth infections including schistosomiasis. Surprisingly, insect-derived compounds have largely been neglected so far in the search for novel anthelminthics, despite the generally recognized high potential of insect biotechnology for drug discovery. This motivated us to assess the antischistosomal capacity of harmonine, an antimicrobial alkaloid from the harlequin ladybird Harmonia axyridis that raised high interest in insect biotechnology in recent years. We observed remarkably pleiotropic effects of harmonine on physiological, cellular, and molecular processes in adult male and female Schistosoma mansoni at concentrations as low as 5 µM in vitro. This included tegumental damage, gut dilatation, dysplasia of gonads, a complete stop of egg production at 10 µM, and increased production of abnormally shaped eggs at 5 µM. Motility was reduced with an EC50 of 8.8 µM and lethal effects occurred at 10-20 µM within 3 days of culture. Enzyme inhibition assays revealed acetylcholinesterase (AChE) as one potential target of harmonine. To assess possible effects on stem cells, which represent attractive anthelminthic targets, we developed a novel in silico 3D reconstruction of gonads based on confocal laser scanning microscopy of worms after EdU incorporation to allow for quantification of proliferating stem cells per organ. Harmonine significantly reduced the number of proliferating stem cells in testes, ovaries, and also the number of proliferating parenchymal neoblasts. This was further supported by a downregulated expression of the stem cell markers nanos-1 and nanos-2 in harmonine-treated worms revealed by quantitative real-time PCR. Our data demonstrate a multifaceted antischistosomal activity of the lady beetle-derived compound harmonine, and suggest AChE and stem cell genes as possible targets. Harmonine is the first animal-derived alkaloid detected to have antischistosomal capacity. This study highlights the potential of exploiting insects as a source for the discovery of anthelminthics.


Assuntos
Alcenos/farmacologia , Anti-Helmínticos/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Alcenos/isolamento & purificação , Animais , Anti-Helmínticos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Besouros/química , Feminino , Masculino , Testes de Sensibilidade Parasitária , Reprodução/efeitos dos fármacos , Schistosoma mansoni/fisiologia , Células-Tronco/efeitos dos fármacos , Análise de Sobrevida
12.
J Ethnopharmacol ; 235: 489-500, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30763693

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The whole plant of Andrographis paniculata (Burm. f.) Wall.ex Nees is used traditionally in different forms by the local people of Asian countries owing to its myriad medicinal properties. Its use as an anthelmintic has been mentioned in literature but has not been well elucidated. AIM OF THE STUDY: To determine anthelmintic effects of extracts from leaves of A.paniculata against human hookworm species based on a standard assay system and to establish the effects of major active compounds responsible for the effects. MATERIALS AND METHODS: Ovicidal and larvicidal activities of extracts of leaves of A.paniculata in different solvents ethanol (Et), methanol (Met), ethyl acetate (EA) and petroleum ether (PE) was studied against field isolates of Ancylostoma duodenale collected and cultivated from hookworm infected human stool samples by egg hatch and larval motility assays. Major active compounds namely andrographolide (AP1), neoandrographolide (AP2) and andrograpanin (AP3) were estimated quantitatively in all the extracts by high-performance liquid chromatography (HPLC) and mass spectrometry (MS) analysis. Anthelmintic effects (ED50, LC50) and presence of the marker compounds in each extract was statistically analyzed by principal component analysis (PCA). Further, biological activities of pure compounds of AP1, AP2, AP3 were assessed to validate the results of the study. RESULTS: Extracts in ethanol and methanol showed highest activity in inhibition of egg hatching with lowest ED50 values (0.017 and 0.02 mg/mL respectively) while ethyl acetate extract had the highest activity against larval motility (0.001 mg/mL) followed by ethanol (0.019 mg/mL). On HPLC analysis, andrographolide content (%), the major diterpene compound, in Met and Et was 0.85 and 1.43 respectively. On PCA, andrographolide component in the extracts was associated with significant inhibitory effects both on egg hatching and larval motility. Pure compound AP1 also showed significant ovicidal and larvicidal activities at concentrations 0.125 µg/mL and 0.019 mg/mL respectively. CONCLUSION: Andrographolide is one of the main phytochemical responsible for significant ovicidal and larvicidal activity against field isolates of A.duodenale from human infections and can be developed as a potential therapeutic choice.


Assuntos
Ancylostoma/efeitos dos fármacos , Andrographis/química , Infecções por Uncinaria/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Cromatografia Líquida de Alta Pressão , Infecções por Uncinaria/parasitologia , Humanos , Dose Letal Mediana , Espectrometria de Massas , Extratos Vegetais/administração & dosagem , Folhas de Planta , Análise de Componente Principal , Solventes/química
13.
Acta Parasitol ; 64(1): 152-161, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30671769

RESUMO

BACKGROUND: Chamomile (Matricaria recutita L.) is a plant which has been reported to be effective in treating several parasitic and digestive diseases. The present study was conducted to evaluate the anthelmintic activity of chamomile methanolic extract (CME). METHODS: In vitro, the anthelmintic activities of CME were investigated on the L3 larvae of Heligmosomoides polygyrus in comparison to albendazole. In vivo, Swiss albino mice were infected with infective third (L3) larval stage of H. polygyrus by intragastric administration. Moreover, the effect of CME and albendazole on worm eggs, adult worms, serum cytokine production, and oxidative stress was studied. RESULTS: All used doses of CME showed a potent anthelmintic activity both in vitro and in vivo and the effect being similar to treatment with albendazole. Moreover, H. polygyrus infestation was accompanied by an intestinal oxidative stress status characterized by an increased lipoperoxidation, a depletion of antioxidant enzyme activity, as well as an overload of hydrogen peroxide. We have also recorded an increase of pro-inflammatory mediator (TNF-α, IL-6, and IL-1ß) levels after treatment with CME (14 ± 0.8; 41 ± 2; 58 ± 4 pg/mg protein, respectively, with the concentration 800 mg/kg, body weight) when compared with infected control mice (20 ± 1; 59 ± 2, and 83 ± 4 pg/mg protein, respectively). However, extract treatment alleviated all the deleterious effects associated with H. polygyrus infection. CONCLUSION: These findings suggest that CME can be used in the control of gastrointestinal helminthiasis and associated oxidative stress.


Assuntos
Anti-Helmínticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Camomila/química , Inflamação/patologia , Nematospiroides dubius/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Infecções por Strongylida/tratamento farmacológico , Animais , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Camundongos , Testes de Sensibilidade Parasitária , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/análise , Infecções por Strongylida/patologia , Resultado do Tratamento
14.
J Agric Food Chem ; 67(1): 520-530, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30516988

RESUMO

In this work, a restricted access volatile supramolecular solvent (RAM-VOL-SUPRAS) directly synthesized in milk is proposed for the first time for the simultaneous extraction and cleanup of benzimidazole anthelmintic drugs in milk meant for human consumption. The RAM-VOL-SUPRAS was formed by the self-assembly and coacervation of hexanol in tetrahydrofuran induced by the water content in milk. Benzimidazoles legislated by the European Union were quantitatively extracted (80-110%), and proteins were precipitated by the action of THF and the amphiphile; extraction of carbohydrates was avoided by a size exclusion mechanism, and lipids were removed during hexanol evaporation. The analytical methodology was fully validated according to Commission Decision 2002/657/EC. Method detection limits from 0.03 to 0.14 µg L-1 were well below the maximum residue limits legislated in milk for these drugs, with interday precisions at maximum residue levels below 13%. This novel methodology guarantees a rapid and reliable tool for daily and routine laboratory analyses in the field of food quality control.


Assuntos
Anti-Helmínticos/análise , Anti-Helmínticos/isolamento & purificação , Benzimidazóis/análise , Benzimidazóis/isolamento & purificação , Leite/química , Extração em Fase Sólida/métodos , Animais , Bovinos , Cromatografia Líquida , Contaminação de Alimentos/análise , Furanos/química , Hexanóis/química , Limite de Detecção , Extração em Fase Sólida/instrumentação , Solventes/química , Espectrometria de Massas em Tandem , Compostos Orgânicos Voláteis/química
15.
ACS Infect Dis ; 5(1): 102-110, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30398059

RESUMO

As part of the control and elimination strategy of human schistosomiasis, preventive chemotherapy relies on a single drug, praziquantel. Facing an almost dry drug development pipeline, screening the Pathogen Box from the Medicines for Malaria Venture (MMV), provides a unique opportunity to possibly expand the pool of potent molecules against schistosomiasis. The activity of 400 compounds from this open-access library was first screened in vitro on the larval stage of Schistosoma mansoni. The hits were then tested on adult worms. Eleven leads were identified and tested for albumin-binding and activity on adult S. haematobium. In parallel, a rudimental structure-activity relationship analysis was performed on the 112 available analogues of three leads, yielding another 30 molecules active against both larval and adult stages of S. mansoni. Seven leads, selected on druglikeness, pharmacokinetic properties, and availability, plus auranofin were tested in mice harboring a chronic S. mansoni infection. MMV022029 and MMV022478 revealed the highest worm burden reductions of 67.8 and 70.7%, respectively. This study provided a series of new potent scaffolds and pharmacophores that could be used to design and develop suitable alternative(s) to praziquantel.


Assuntos
Anti-Helmínticos/farmacologia , Antimaláricos/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacocinética , Antimaláricos/farmacocinética , Descoberta de Drogas , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Concentração Inibidora 50 , Larva/efeitos dos fármacos , Malária/tratamento farmacológico , Camundongos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/isolamento & purificação , Relação Estrutura-Atividade
16.
J Helminthol ; 93(3): 286-294, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29655377

RESUMO

Despite the seriousness of schistosomiasis, its treatment depends only on praziquantel (PZQ), which has begun to lose its efficacy against the emergent Schistosoma mansoni-resistant strains. Therefore, the discovery of a novel schistosomicidal drug is an urgent priority. This study was designed to evaluate treatment with Cucurbita pepo L. (pumpkin) seed oil (PSO) alone and combined with PZQ against S. mansoni in experimentally infected mice. The study involved five groups: GI was the normal control; GII was the infected control; GIII was treated with an oral dose of PZQ of 500 mg/kg/day for two successive days, starting in the sixth week post infection; GIV was treated with an oral dose of PSO of 50 mg/kg/day for four weeks, starting in the fourth week post infection; and GV was treated with combined PSO-PZQ. Worm burden, tissue egg load and oogram pattern were estimated, and the ultrastructure alterations were examined. Histopathological examination of granuloma diameters, collagen deposition (Picro Sirius red stain), and angiogenesis (immunohistochemical expression of CD34+) was conducted and serum liver enzymes were measured to assess the liver condition. Moreover, the oxidative stress was evaluated by determining the amounts of malondialdehyde and superoxide dismutase in liver homogenates. The results revealed significant changes in all the assessed parameters with PSO administration. However, PZQ was significantly more effective as an antiparasitic agent, whereas PSO was better in terms of fibrosis and oxidative stress. The most significant results were obtained in group V, which may be attributed to a synergy between PZQ and PSO, with antiparasitic, antioxidant and antifibrotic properties.


Assuntos
Anti-Helmínticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Cucurbita/química , Óleos Vegetais/administração & dosagem , Praziquantel/administração & dosagem , Esquistossomose mansoni/tratamento farmacológico , Animais , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Modelos Animais de Doenças , Quimioterapia Combinada , Camundongos , Óleos Vegetais/isolamento & purificação , Óleos Vegetais/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Sementes/química , Resultado do Tratamento
17.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 30(5): 500-503, 2018 Nov 07.
Artigo em Chinês | MEDLINE | ID: mdl-30567018

RESUMO

OBJECTIVE: To detect the molecular characterization of polysaccharide purified from Amusium pleuronectes, so as to investigate its role of intervention to the formation of hepatic fibrosis caused by Schistosoma japonicum infection. METHODS: The crude polysaccharide from A. pleuronectes was extracted and further purified, and the molecular weight and monosaccharide composition were determined by the high pressure size exclusion chromatography and PMP pre-column derivatization method, respectively. A total of 50 female BALB/c mice were randomly divided into five groups:A (normal group), B (experimental group), C (polysaccharide group), D (praziquantel), and E (polysaccharide + praziquantel group). The mice in B, C, D, or E groups were attacked on the abdominal skin by using the cercariae of S. japonicum (30 ± 2 for each mouse) respectively. After 8 weeks, the mice in C, D, and E groups were administrated by polysaccharide and/or praziquantel, and the mice in B group were instead of saline. All the livers and sera were collected after 16 weeks. HE staining was employed for the livers, and serum IFN-γ and IL-13 were measured by using ELISA kits. RESULTS: The molecular weight of purified polysaccharide from A. pleuronectes was 11.7 kDa. Compared with A and B groups, the serum levels of IFN-γ in C, D, and E groups were significantly increased (F = 63.525, P < 0.01). However, the serum levels of IL-13 in C, D, and E groups were significantly decreased (F = 99.788, P < 0.01) compared with that in B group. HE staining showed that the egg nodules and hepatic fibrosis were observed in B, C, D, and E groups. The number of egg nodules and fibrosis degree in E group were milder than those in B group (χ2 = 7.875, P < 0.05). CONCLUSIONS: The polysaccharide from A. pleuronectes has an obvious effect in preventing hepatic fibrosis process induced by S. japonicum infection, particularly combining with the administration of praziquantel.


Assuntos
Bivalves , Cirrose Hepática , Polissacarídeos , Schistosoma japonicum , Esquistossomose Japônica , Animais , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/uso terapêutico , Bivalves/química , Feminino , Cirrose Hepática/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Praziquantel/uso terapêutico , Distribuição Aleatória , Ratos
18.
Int J Parasitol Drugs Drug Resist ; 8(3): 494-495, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30429103

RESUMO

The third scientific meeting in the series "Anthelmintics: From Discovery to Resistance" was held in Indian Rocks Beach, Florida, at the end of January 2018. The meeting focused on a variety of topics related to the title, including the identification of novel targets and new leads, the mechanism of action of existing drugs and the genetic basis of resistance against them. Throughout there was an emphasis on the exploitation of new technologies and methods to further these aims. The presentations, oral and poster, covered basic, veterinary and medical science with strong participation by both academic and commercial researchers. This special issue contains selected papers from the meeting.


Assuntos
Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Descoberta de Drogas , Animais , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Congressos como Assunto , Sistemas de Liberação de Medicamentos/métodos , Humanos , Canais Iônicos/uso terapêutico
19.
Parasit Vectors ; 11(1): 605, 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482220

RESUMO

BACKGROUND: Human schistosomiasis is a neglected tropical disease caused by parasitic worms of the genus Schistosoma that still affects some 200 million people. The mainstay of schistosomiasis control is a single drug, praziquantel. The reliance on this drug carries a risk of resistance emerging to this anthelmintic, such that research towards alternative anti-schistosomal drugs is warranted. In this context, a number of studies have employed computational approaches to prioritise proteins for investigation as drug targets, based on extensive genomic, transcriptomic and small-molecule data now available. METHODS: Here, we established a customisable, online application for the prioritisation of drug targets and applied it, for the first time, to the entire inferred proteome of S. haematobium. This application enables selection of weighted and ranked proteins representing potential drug targets, and integrates transcriptional data, orthology and gene essentiality information as well as drug-drug target associations and chemical properties of predicted ligands. RESULTS: Using this application, we defined 25 potential drug targets in S. haematobium that associated with approved drugs, and 3402 targets that (although they could not be linked to any compounds) are conserved among a range of socioeconomically important flatworm species and might represent targets for new trematocides. CONCLUSIONS: The online application developed here represents an interactive, customisable, expandable and reproducible drug target ranking and prioritisation approach that should be useful for the prediction of drug targets in schistosomes and other species of parasitic worms in the future. We have demonstrated the utility of this online application by predicting potential drug targets in S. haematobium that can now be evaluated using functional genomics tools and/or small molecules, to establish whether they are indeed essential for parasite survival, and to assist in the discovery of novel anti-schistosomal compounds.


Assuntos
Anti-Helmínticos/farmacologia , Biologia Computacional/métodos , Sistemas de Liberação de Medicamentos/métodos , Sistemas On-Line , Schistosoma haematobium/efeitos dos fármacos , Esquistossomose Urinária/tratamento farmacológico , Animais , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/uso terapêutico , Sistemas de Liberação de Medicamentos/instrumentação , Genômica , Humanos , Ligantes , Anotação de Sequência Molecular , Doenças Negligenciadas/tratamento farmacológico , Praziquantel/farmacologia , Proteoma , Schistosoma haematobium/genética , Transcrição Genética
20.
Comput Biol Chem ; 77: 363-372, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30466045

RESUMO

Schistosomiasis, a chronic neglected tropical disease caused by the Schistosoma spp. parasite, is associated with disabling patient symptoms. The new focus of the WHO roadmap on 'transmission control, wherever possible' offers drug development opportunities for intermediate-host control to prevent human-to-snail-to-human parasite transmission. Reports on the analysis of the impact of 'chemical-based mollusciciding' have concluded that constant application of molluscicides may contribute significantly towards the elimination of schistosomiasis in endemic areas. In South-Western Nigeria, Tetrapleura tetraptera is a tree whose fruit has been widely used in snail vector control. The presence of molluscicidal N-acetyl triterpene glycosides in the fruit has been reported. In this study, a bioactivity-directed fractionation of the fruit extract was performed to isolate the most potent molluscicidal saponin from the fruit. In an attempt to provide mechanistic insight into the observed activity, in silico screening was performed, profiling the molluscicidal N-acetyl triterpene glycosides reported from the fruit against two potential therapeutic targets in the mollusk used, NADH-ubiquinone oxidoreductase (NAD1) and retinoid X receptor. The docking predicted binary complexes of the saponins, which were subjected to explicit solvent conformational sampling from which patterns of structural stability were obtained. The binding energies alone did not account for the potency of the saponins indicating the influence of other factor like pharmacokinetic parameters. The study concluded that there is a preferential suitability of ND1's MWFE site for the rational design and development of novel molluscicidal agents.


Assuntos
Vetores de Doenças , Saponinas/química , Saponinas/toxicidade , Esquistossomose/prevenção & controle , Esquistossomose/transmissão , Caramujos/efeitos dos fármacos , Acetilação , Animais , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/toxicidade , Frutas/química , Humanos , Modelos Moleculares , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Saponinas/isolamento & purificação , Caramujos/fisiologia , Tetrapleura/química
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