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1.
AAPS PharmSciTech ; 22(8): 259, 2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34704177

RESUMEN

Cliv-92 is a mixture of three structurally similar coumarinolignoids and a proven hepatoprotective agent. Low aqueous solubility and poor bioavailability are notable hindrances for its further use. Therefore, glycyrrhetinic acid-linked chitosan nanoparticles loaded with Cliv-92 were prepared for active targeting to the liver. The nanoparticles were prepared by the ionic gelation method to avoid the use of toxic solvents/rigorous agitation. The method of preparation was optimized using a central composite design with independent variables, namely polymer: drug ratio (3:1, w/w), crosslinker concentration (0.5%), and stirring speed (750 rpm). The optimized nanoparticles had a mean particle size of 185.17 nm, a polydispersity index of 0.41, a zeta potential of 30.93 mV, and a drug loading of 16.30%. The prepared formulation showed sustained release of approximately 63% of loaded Cliv-92 over 72 h. The nanoparticles were freeze-dried for long-term storage and further characterized. The formulation was found to be biocompatible for parenteral delivery. In vivo imaging study showed that optimized nanoparticles were preferentially accumulated in the liver and successfully targeting the liver. The present study successfully demonstrated the improved pharmacokinetic properties (≈12% relative bioavailability) and efficacy profile (evidenced by in vivo and histopathological studies) of fabricated Cliv-92 nanoparticles.


Asunto(s)
Quitosano , Ácido Glicirretínico , Nanopartículas , Portadores de Fármacos , Tamaño de la Partícula , Solubilidad
2.
J Asian Nat Prod Res ; 18(2): 172-83, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26527419

RESUMEN

Saraca asoca bark has been used in the Ayurvedic system of medicine for female urino-genital disorders. We have recently reported the isolation and characterization of several compounds as markers to develop HPLC profiling of its methanol and aqueous methanol extracts. Now, a HPLC-PDA inactive compound, (+)-pinitol has been isolated and characterized from the bark of this medicinally important tree. Pinitol is a well known bioactive compound for a variety of biological activities, including hypoglycemic and anti-inflammatory activities. A process for the isolation of relatively good concentration of (+)-pinitol from S. asoca bark has been developed and its in vitro anti TNF-α and anti-inflammatory activities against carragenan-induced edema confirmed. While conducting experiments on the possible agonistic activity, it was found that (+)-pinitol showed up to eight fold reduction in the doses of ß-lactam antibiotics. The mechanism of its agonistic activity was studied by docking experiments which showed that different conformations of (+)-pinitol and antibiotics were actually in the same binding site with no significant change in the binding energy. These docking simulations, thus predict the possible binding mode of studied compounds and probable reason behind the synergistic effect of (+)-pinitol along with ß-lactam antibiotics.


Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Fabaceae/química , Inositol/análogos & derivados , beta-Lactamas/aislamiento & purificación , beta-Lactamas/farmacología , Animales , Antibacterianos/química , Antiinflamatorios/química , Carragenina/farmacología , Cromatografía Líquida de Alta Presión , Edema/inducido químicamente , Edema/tratamiento farmacológico , Femenino , Humanos , India , Inositol/farmacología , Lipopolisacáridos/farmacología , Medicina Ayurvédica , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Corteza de la Planta/química , Ratas , Estereoisomerismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , beta-Lactamas/química
3.
Front Nutr ; 9: 1038902, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36386946

RESUMEN

Vitamin B12 deficiency is prevalent among individuals globally. Inadequate consumption of B12 rich diet and low bioavailability (due to diet based/physiological factors) are linked to the deficiency of Vitamin B12 inside the body. Bioavailability enhancers augment the bioavailability of an ingested substance (drug/nutrient) thus increasing their concentration inside the body and maximizing their therapeutic benefits. In traditional medicine, Licorice (Glycyrrhiza glabra) finds utility in the treatment of various health conditions. Thus, the present study aimed to examine the potential of ethanolic extract obtained from G. glabra roots to enhance the bioavailability of Vitamin B12. The effect of ethanolic extract of G. glabra (GgEtOH) on intestinal absorption enhancement of B12 was assessed in vitro on Caco-2 and ex-vivo everted gut sac models. The influence of extract on the pharmacokinetics of Vitamin B12 was determined in vivo in Swiss albino mice. GgEtOH significantly enhanced the permeation (Papp) of B12 by 2-5 fold in vitro (25, 50, and 100 µg/ml concentrations) and ex-vivo (250 and 500 µg/ml concentrations). The pharmacokinetic parameters of B12 such as Cmax, AUC, Tmax, etc. were also significantly elevated in vivo upon oral administration of B12 (1 mg/kg dose) in combination with GgEtOH (100 and 1,000 mg/kg dose). These preliminary findings indicate that the ethanolic extract of G. glabra is capable of enhancing the bioavailability of Vitamin B12. To the best of our knowledge, this is the first report to demonstrate herbal extract-mediated enhancement of Vitamin B12 bioavailability through in vitro, ex vivo, and in vivo assays.

4.
Biomed Chromatogr ; 25(6): 641-5, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20845375

RESUMEN

The influence of active fraction isolated from pods of an indigenous plant, Moringa oleifera (MoAF) was studied on the pharmacokinetic profile of the orally administered frontline anti-tuberculosis drug rifampicin (20 mg/kg b.w.) in Swiss albino mice. The antibiotic rifampicin alone and in combination with MoAF (0.1 mg/kg b.w.) was administered orally and heparanized blood samples were collected from the orbital plexus of mice for plasma separation at 0, 1, 2, 3, 4 and 5 h, post treatment. Plasma rifampicin concentration, pharmacokinetic parameters and drug metabolizing enzyme (cytochrome P-450) activity were determined. The pharmacokinetic data revealed that MoAF-treated animals had significantly increased rifampicin plasma concentration, C(max), K(el), t(½(a)), t(½(el)), K(a) and AUC as well as inhibited rifampicin-induced cytochrome P-450 activity. In conclusion, the result of this study suggested that the bioavailability-enhancing property of MoAF may help to lower the dosage level and shorten the treatment course of rifampicin.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Moringa oleifera/química , Extractos Vegetales/farmacología , Rifampin/farmacocinética , Animales , Área Bajo la Curva , Disponibilidad Biológica , Sistema Enzimático del Citocromo P-450/metabolismo , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Femenino , Masculino , Ratones , Microsomas Hepáticos/química , Microsomas Hepáticos/enzimología , Rifampin/sangre
5.
Pharm Biol ; 49(6): 669-73, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21554010

RESUMEN

CONTEXT: Cancer chemopreventive action of walnut [Juglans regia L. (Juglandaceae)] has been explored. OBJECTIVE: This study evaluated antiproliferative and antioxidant activities of walnut. MATERIALS AND METHODS: Various fractions of walnut extract have been screened for antiproliferative activity against human cancer cell lines using the MTT assay. All these fractions have also been evaluated for total phenolic content, antioxidant activity, and reducing power capacity. RESULTS AND DISCUSSION: Chloroform and ethyl acetate fractions exhibited a high level of antiproliferation against HepG-2, liver cancer cell line (IC(50) = 9 and 15 µg/mL, respectively). CONCLUSION: Exhibiting high phenolic content, antioxidant activity, and potent antiproliferative activity, walnut may act as a cancer chemopreventive agent.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Frutas/química , Juglans/química , Extractos Vegetales/farmacología , Acetatos/química , Antineoplásicos Fitogénicos/química , Antioxidantes/química , Cloroformo/química , Ensayos de Selección de Medicamentos Antitumorales/métodos , Ácido Elágico/química , Ácido Gálico/química , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Oxidación-Reducción/efectos de los fármacos , Fenoles/química , Extractos Vegetales/química
6.
Curr Top Med Chem ; 21(8): 686-695, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33280598

RESUMEN

BACKGROUND: Liver cancer is ranked as the fifth most prevalent and third most lethal cancer worldwide. The incidence rates of this cancer are on the rise, and only limited treatment options are available. METHODS: To identify and optimize the inhibitors of liver cancer cell-lines, a QSAR model was developed by using multiple linear regression methods. The robustness of the model was validated through statistical methods and wet-lab experiments. RESULTS: The developed QSAR models yielded high activity descriptor relationship accuracy of 91%, referred to by regression coefficient (r2= 0.91), and a high activity prediction accuracy of 89%. The external predicted (pred_r2) ability of the model was found to be 90%. CONCLUSION: The QSAR study indicates that chemical descriptors such as to measure of electronegative atom count (Epsilon3), atom type count descriptors (MMFF_10), number of a carbon atom connected with four single bonds (SssssCE- index), molecular weight and, number of oxygen atom connected with two aromatic bonds (SaaOE-index) are significantly correlated with anticancer activity. The model, which was validated statistically and through wet-lab experiments, was further used in the virtual screening of potential inhibitors against the liver cancer cell line WRL68. ADMET risk screening, synthetic accessibility, and Lipinski's rule of five are used to filter false positive hits. AfterwardS, to achieve a set of aligned ligand poses and rank the predicted active compounds, docking studies were carried out. The studied compounds and their metabolites were also analyzed for different pharmacokinetics parameters. Finally, a series of compounds was proposed as anticancer agents.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Hepáticas/patología , Antineoplásicos/química , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Humanos , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad Cuantitativa , Reproducibilidad de los Resultados
7.
Biomed Pharmacother ; 144: 112302, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34678731

RESUMEN

Malaria eradication is still a major global health problem in developing countries, which has been of more concern ever since the malaria parasite has developed resistance against frontline antimalarial drugs. Historical evidence proves that the plants possess a major resource for the development of novel anti-malarial drugs. In the present study, the bioactivity guided fractionation of the oleogum-resin of Boswellia serrata Roxb. yielded the optimum activity in the ethyl acetate fraction with an IC50 of 22 ± 3.9 µg/mL and 26.5 ± 4.5 µg/mL against chloroquine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum respectively. Further, upon fractionation, the ethyl acetate fraction yielded four major compounds, of which 3-Hydroxy-11-keto-ß-boswellic acid (KBA) was found to be the most potent with IC50 values 4.5 ± 0.60 µg/mL and 6.25 ± 1.02 µg/mL against sensitive and resistant strains respectively. KBA was found to inhibit heme detoxification pathways, one of the most common therapeutic targets, which probably lead to an increase in reactive oxygen species (ROS) and nitric oxide (NO) detrimental to P. falciparum. Further, the induced intracellular oxidative stress affected the macromolecules in terms of DNA damage, increased lipid peroxidation, protein carbonylation as well as loss of mitochondrial membrane potential. However, it did not exhibit any cytotoxic effect in VERO cells. Under in vivo conditions, KBA exhibited a significant reduction in parasitemia, retarding the development of anaemia, resulting in an enhancement of the mean survival time in Plasmodium yoelii nigeriensis (chloroquine-resistant) infected mice. Further, KBA did not exhibit any abnormality in serum biochemistry of animals that underwent acute oral toxicity studies at 2000 mg/kg body weight.


Asunto(s)
Antimaláricos/farmacología , Boswellia , Hemo/metabolismo , Malaria/tratamiento farmacológico , Extractos Vegetales/farmacología , Plasmodium falciparum/efectos de los fármacos , Plasmodium yoelii/efectos de los fármacos , Triterpenos/farmacología , Animales , Antimaláricos/aislamiento & purificación , Antimaláricos/toxicidad , Boswellia/química , Chlorocebus aethiops , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Malaria/sangre , Malaria/parasitología , Ratones , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Plasmodium falciparum/metabolismo , Plasmodium falciparum/patogenicidad , Plasmodium yoelii/metabolismo , Plasmodium yoelii/patogenicidad , Carbonilación Proteica/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Resinas de Plantas , Triterpenos/aislamiento & purificación , Triterpenos/toxicidad , Células Vero
8.
Nat Prod Res ; 34(18): 2647-2651, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30663356

RESUMEN

A polyphenolic flavonoid, Silymarin isolated from Silybum marianum is widely known for its hepatoprotective action. In the present study anti-plasmodial activity of Silymarin has been demonstrated for the first time having IC50 of 14 ± 0.33 µM against the NF-54 strain of P. falciparum with high selectivity index (>100). The parasitostatic action is exerted through inhibition of ß-hematin/hemozoin formation which is due to the interaction (Kd = 3.63 ± 0.9µM) of silymarin with free heme in a Stoichiometry of 1:1 Silymarin: heme complex resulting into heme-induced membrane damage in the parasite. Silymarin could hinder the glutathione and hydrogen peroxide-induced heme detoxification. Silymarin also induces apoptosis in the parasite through the elevation of caspase-3 level in a dose-dependent manner. Results from the docking studies suggest that Silymarin interacts with heme.


Asunto(s)
Flavonoides/farmacología , Hemo/metabolismo , Plasmodium falciparum/efectos de los fármacos , Silimarina/farmacología , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Hemoproteínas/antagonistas & inhibidores , Concentración 50 Inhibidora , Plasmodium falciparum/crecimiento & desarrollo , Silimarina/química , Silimarina/metabolismo
9.
Food Chem ; 284: 171-179, 2019 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-30744843

RESUMEN

Use of harmful chemicals and expensive maintenance of cold-storage conditions for controlling sprouting are among the major problems in potato storage. Here, 20 essential oils (EOs) were tested for their sprouting-inhibiting and sprouting-inducing activities. Overall, treatments of lemon grass (LG) and clove (CL) oils could induce sprouting whereas palmarosa (PR) and ajwain (AZ) oils could inhibit sprouting of potato tubers at normal-room-temperature (25 ±â€¯2 °C) storage. Selected-EOs treatments affected sprouting by modulation of accumulation of reducing sugars, ethylene, and expression of genes involved in tuber-sprouting such as ARF, ARP, AIP and ERF. Surprisingly, 7-days AZ-treatments could inhibit sprouting for 30-days which was mediated via damaging apical meristem. However, LG- and CL-treated tubers could produce enhanced potato yield as well. Present work clearly demonstrates that selected-EOs can be used as a promising eco-friendly approach for inducing/inhibiting sprouting of potato tubers during potato storage and those enhancing sprouting can be used for enhancing productivity.


Asunto(s)
Aceites Volátiles/farmacología , Solanum tuberosum/efectos de los fármacos , Solanum tuberosum/fisiología , Aceite de Clavo/farmacología , Cymbopogon/química , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Meristema/efectos de los fármacos , Tubérculos de la Planta/efectos de los fármacos , Tubérculos de la Planta/crecimiento & desarrollo , Tubérculos de la Planta/metabolismo
10.
Biomed Pharmacother ; 97: 1654-1662, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29793328

RESUMEN

Malaria the parasitic disease of tropical countries is seeking newer therapeutic strategies owing to the drug resistance to existing drugs. The pathogenesis after infection renders the host to oxidative stress resulting in an altered immune status. Natural products rich in phenols are a source of bio-actives that could have a role in alleviating such condition. The present study reports the phenol rich ethyl acetate extract from the petals of Rosa damascena (RdEa) to be active against Plasmodium falciparum in-vitro and Plasmodium berghei in-vivo. It restores the haemoglobin level while increasing the mean survival time and chemo-suppression in P. berghei infected mice. The HPLC characterised RdEa was found to be rich in Gallic acid and Rutin besides other phenols. RdEa was capable of scavenging the free radicals and modulating the pro-inflammatory mediators (IL6, TNF, IFN and NO) favourably and also restored the architecture of hepatocytes as evidenced through histopathology. The extract was able to arrest the lipopolysaccharide (LPS) induced damage of J774A.1 cells (murine macrophages) and was found to be safe in mice upto 2000 mg/kg body weight.


Asunto(s)
Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Extractos Vegetales/uso terapéutico , Plasmodium falciparum/efectos de los fármacos , Rosa/química , Animales , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Malaria Falciparum/patología , Ratones , Extractos Vegetales/farmacología , Pruebas de Toxicidad Aguda
11.
Front Plant Sci ; 9: 1081, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30150996

RESUMEN

In traditional, herbal medicine, and aromatherapy, use of essential oils and their aroma compounds have been known since long, for the management of various human diseases. The essential oil is a mixture of highly complex, naturally occurring volatile aroma compounds synthesized by medicinal and aromatic plants as secondary metabolites. Essential oils widely used in pharmaceutical, cosmetic, sanitary, food industry and agriculture for their antibacterial, antiviral, antifungal, antiparasitic, insecticidal, anticancer, neuroprotective, psychophysiological, and anti-aging activities. Moreover, volatile aroma compounds comprise a chemically diverse class of low molecular weight organic compounds with significant vapor pressure. However, aroma compounds produced by plants, mainly attract pollinators, seed dispersers and provide defense against pests or pathogens. However, in humans, about 300 active olfactory receptor genes are involved to detect thousands of different aroma compounds and modulates expression of different metabolic genes regulating human psychophysiological activity, brain function, pharmacological signaling, and therapeutic potential. Keeping in mind this importance, present database, namely, AromaDb (http://bioinfo.cimap.res.in/aromadb/) covers information of plant varieties/chemotypes, essential oils, chemical constituents, GC-MS profile, yield variations due to agro-morphological parameters, trade data, aroma compounds, fragrance type, and bioactivity details. The database includes 1,321 aroma chemical structures, bioactivities of essential oil/aroma compounds, 357 fragrance type, 166 commercially used plants, and their high yielding 148 varieties/chemotypes. Also includes calculated cheminformatics properties related to identification, physico-chemical properties, pharmacokinetics, toxicological, and ecological information. Also comprises interacted human genes affecting various diseases related cell signaling pathways correlating the use of aromatherapy. This database could be a useful resource to the plant's growers/producers, an aroma/fragrance industrialist, health professionals, and researchers exploring the potential of essential oils and aroma compounds in the development of novel formulations against human diseases.

12.
Biomed Pharmacother ; 86: 555-561, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28024292

RESUMEN

The study manifests the immunoadjuvant potential of saponin rich fraction from Asparagus racemosus in terms of cellular and humoral immune response that can be exploited against microbial infections. Asparagus racemosus (AR) has been attributed as an adaptogen and rasayana in traditional medication systems for enhancing the host defence mechanism. Spectrophotometric and HPTLC analysis ensured the presence of saponins. The saponin rich fractions were tested for immunoadjuvant property in ovalbumin immunised mice for the humoral response, quantified in terms of prolonged antibody production upto a duration of 56days. Proinflammatory cytokines (IL-6 and TNF) were estimated for the cellular immune response in LPS stimulated primary murine macrophages. The safety evaluation in terms of cytotoxicity and allergic response has also been evaluated through in-vitro (MTT) and in-vivo (IgE) respectively. ARS significantly inhibited the pro-inflammatory cytokines, in LPS stimulated murine macrophages with no intrinsic cytotoxicity. The significant increase in IgG production infers the utility of ARS for prolonged humoral response. Further, the antigen specific response of IL-12 at early stage and IgE titres also suggests the generation of cellular immune response and low allergic reaction respectively, as compared to conventional adjuvants. IL-6 and TNF fluctuations in LPS stimulated and non-stimulated macrophages along with IgG and IL-12 also confirmed the Th1/Th2 modulating effect of ARS. The study indicates potential effect of ARS as an adjuvant for the stimulation of cellular immune response in addition to generating a sustained adaptive response without any adverse effects paving way for further validation with pathogenic organisms.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Formación de Anticuerpos/inmunología , Asparagus/inmunología , Citocinas/inmunología , Hipersensibilidad/inmunología , Inflamación/inmunología , Saponinas/inmunología , Inmunidad Adaptativa/inmunología , Animales , Femenino , Inmunoglobulina G/inmunología , Interleucina-12/inmunología , Interleucina-6/inmunología , Macrófagos/inmunología , Masculino , Ratones , Factores de Necrosis Tumoral/inmunología
13.
Phytomedicine ; 23(6): 654-61, 2016 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-27161406

RESUMEN

BACKGROUND: Staphylococcus aureus infections are raising serious concern across the world. The effectiveness of conventional drugs is continuously decreasing due to global emergence of multidrug resistance (MDR) and therefore, new resistance-modifying agents (RMAs) are highly needed. HYPOTHESIS: Clerodane diterpene 16α-hydroxycleroda-3,13(14)-Z-dien-15,16-olide (CD) from leaves of Polyalthia longifolia (Sonn.) Thwaites (Annonaceae) as RAM will be useful in improving the current treatment strategies for staphylococcal infections. STUDY DESIGN: In the present study, we determine the resistance-modifying activity of CD using clinical isolates of MRSA. Further, the influence of CD on innate immune response was also evaluated in vitro and in vivo. The nature of potential interactions was determined by fractional inhibitory concentration indices (FICIs) calculated from microdilution assays and time-kill curves. RESULTS: The result of in vitro combination study showed that CD significantly reduced MIC of fluoroquinolones up to 16-folds (FICI 0.315-0.500), while in S. aureus infected Swiss albino mice model, combination of CD with norfloxacin, significantly (p<0.01, p<0.001) lowered the systemic microbial burden in blood, liver, kidney, lung and spleen tissues in comparison to CD, norfloxacin alone as well as untreated control. Flow cytometry analysis clearly showed that CD significantly inhibited EtBr efflux and extended post-antibiotic effect. In qRT-PCR analysis, CD alone as well as in combination, significantly modulated the expression of various efflux pump genes including norA up to 2-fold in clinical isolate MRSA-ST2071. Further, the in vitro combination study of the CD (10, 5, 2.5µg/ml) along with the norfloxacin (10µg/ml) depicted a significant decline in the pro-inflammatory cytokines, IL6 and TNF-α. In septic shock mice model, CD did not exhibit any significant changes in the level of pro-inflammatory cytokines. CONCLUSION: This is the first report on drug resistance-modifying potential of CD through inhibition of MDR efflux pump.


Asunto(s)
Antibacterianos/farmacología , Diterpenos de Tipo Clerodano/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Extractos Vegetales/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Animales , Antibacterianos/uso terapéutico , Diterpenos de Tipo Clerodano/aislamiento & purificación , Diterpenos de Tipo Clerodano/uso terapéutico , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Polyalthia/química
14.
Parasitol Int ; 64(1): 118-23, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25449289

RESUMEN

Conyza sumatrensis (Retz.) E.H. Walker (Cs) leaves are used for traditional treatment of malaria in Cameroon. However, the antimalarial activity of the leaf constituents of this plant is still unexplored. The aim of our investigation was to evaluate the antiplasmodial activity of some bioactive constituents from Cs leaves. Compounds were isolated from Cs leaves and structurally elucidated using extensive spectroscopic analysis. The in vitro antiplasmodial activity of the extracts and pure compounds were evaluated on chloroquine-sensitive strain (NF54) of Plasmodium falciparum. The in vivo assay was done by administering seven doses of extracts in mice infected with Plasmodium berghei K173 through oral route. Cytotoxicity of pure compounds on murine macrophage cells was performed through [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] (MTT) test. Hemolysis and lactate dehydrogenase assays were also carried out using standard procedures. The in silico prediction of bioactive constituents was performed through Autodock Vina. Polarity-based extracts from Cs were found to be active against P. falciparum (NF54) and P. berghei (K173) in vitro and in vivo respectively. Further, bioactivity-guided isolation of n-hexane fraction yielded three compounds, (1), (2) and (3) with IC50 of 34, 17.9 and 18µg/ml, respectively, while the ethyl acetate fraction afforded the fourth compound with an IC50 of 25µg/ml, indicating anti-malarial potential of Cs through PfLDH interaction without compromising normal cell growth. This study reports for the first time, the antiplasmodial activity of bioactive constituents from Cs and confirms its traditional use.


Asunto(s)
Antimaláricos/aislamiento & purificación , Antimaláricos/uso terapéutico , Conyza/química , Malaria/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Plasmodium berghei/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/farmacología , Camerún , Simulación por Computador , Eritrocitos/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Masculino , Ratones , Pruebas de Sensibilidad Parasitaria , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química
15.
Curr Drug Targets ; 15(4): 374-409, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23848395

RESUMEN

Because of mutation and natural selection, development of drug resistance to the existing antimalarial is the major problem in malaria treatment. This problem has created an urgent need of novel antimalarial drug targets as well as lead compounds. The important characteristic of malaria is that it shows the phenomenon of balanced polymorphisms. Several traits have been selected in response to disease pressure. Therefore such factors must be explored to understand the pathogenesis of malaria infection in human host. Apicoplast, hub of metabolism is present in Plasmodium falciparum (causative agent of falciparum malaria) having similarities with plant plastid. Among several pathways in apicoplast, Dolichol metabolic pathway is one of the most important pathway and has been known to play role in parasite survival in the human host. In P.falciparum, a phosphorylated derivative of Dolichol participates in biosynthesis of glycoproteins. Several proteins of this pathway play role in post translational modifications of proteins involved in the signal transduction pathways, regulation of DNA replication and cell cycle. This pathway can be used as antimalarial drug target. This report has explored progress towards the study of proteins and inhibitors of Dolichol metabolic pathway. For more comprehensive analysis, the host genetic factors and drug-protein interaction have been covered.


Asunto(s)
Antimaláricos/farmacología , Apicoplastos/metabolismo , Dolicoles/análogos & derivados , Malaria Falciparum/tratamiento farmacológico , Plasmodium falciparum/metabolismo , Proteínas Protozoarias/genética , Ciclo Celular/efectos de los fármacos , Replicación del ADN/efectos de los fármacos , Dolicoles/genética , Dolicoles/metabolismo , Diseño de Fármacos , Genes Protozoarios , Variación Genética , Humanos , Malaria Falciparum/metabolismo , Malaria Falciparum/patología , Fosforilación , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/patogenicidad , Polimorfismo de Nucleótido Simple , Proteínas Protozoarias/química , Proteínas Protozoarias/metabolismo , Transducción de Señal/efectos de los fármacos
16.
J Ethnopharmacol ; 149(3): 797-802, 2013 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-23954323

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Many of the effective therapeutic strategies have been derived from ethnopharmacologically used natural products. Pluchea lanceolata is an herb employed in Indian folk medicine for malaria like fever but it lacks proper pharmacological intervention. AIM OF THE STUDY: To evaluate antimalarial and safety profile of Pluchea lanceolata: an in-vitro, in-vivo for its ethnopharmacological validation. MATERIALS AND METHODS: Methanol, butanol, ethyl acetate, chloroform, hexane extracts and its isolate, taraxasterol acetate (TxAc) were obtained from air dried aerial part of Pluchea lanceolata. These were tested in-vitro against chloroquine-sensitive strain of Plasmodium falciparum NF54 by measuring the parasite specific lactate dehydrogenase activity. The most potent hexane extract and TxAc were further validated for in-vivo antimalarial and safety evaluation. TxAc, a pentacyclic-triterpene isolated from the most active fraction was further evaluated with special emphasis on inflammatory mediators involved in malaria pathogenesis. Murine malaria was induced by intra-peritoneal injection of Plasmodium berghei infected red blood cells to the male Swiss inbred mice. Mice were orally treated following Peters 4-Day suppression test. In-vivo antimalarial efficacy was examined by evaluating the parasitaemia, percent survival, mean survival time, blood glucose, haemoglobin and pro-inflammatory mediators involved in malaria pathogenesis. RESULTS: Hexane extract and TxAc showed promising antimalarial activity in-vitro and in-vivo condition. TxAc attributed in inhibition of the pro-inflammatory cytokines as well as afford to significant increase in the blood glucose and haemoglobin level when compared with vehicle treated infected mice. We have not observed the synergistic action of combinations of chloroquine and TxAc from our experimental results. In-vitro and in-vivo safety evaluation study revealed that hexane extract is non toxic at higher concentration. CONCLUSION: Present study further validates the ancient Indian traditional knowledge and use of Pluchea lanceolata as an antimalarial agent. Study confirms the suitability of Pluchea lanceolata as a candidate for further studies to obtain a prototype for antimalarial medicine.


Asunto(s)
Antimaláricos/uso terapéutico , Asteraceae/química , Malaria/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Animales , Antimaláricos/aislamiento & purificación , Antimaláricos/toxicidad , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citocinas/sangre , Eritrocitos/efectos de los fármacos , Eritrocitos/parasitología , Humanos , Macrófagos Peritoneales/efectos de los fármacos , Malaria/inmunología , Malaria/parasitología , Masculino , Medicina Ayurvédica , Ratones , Componentes Aéreos de las Plantas/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Plasmodium berghei/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Pruebas de Toxicidad Aguda
17.
J Toxicol Sci ; 34(1): 99-108, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19182439

RESUMEN

Chemical characterization and acute and sub-acute toxicity study of Trikatu, a generic herbal formulation of Indian system of medicine, was carried out in Charles Foster (CF) rats for safety profiling. In acute toxicity experiment, Trikatu at 2,000 mg/kg body weight once orally was well tolerated by the experimental animals (both male and female) and no changes were observed in mortality, morbidity, gross pathology, gain in weight, vital organ weight, hematological (total white blood cells (WBC) and red blood cells (RBC) count), biochemical parameters such as serum creatinine, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum lipid profile and tissue biochemical parameters such as reduced glutathione and malonaldehyde content as oxidative stress markers. In sub-acute experiment, Trikatu was administered at 5, 50 and 300 mg/kg body weight once daily for 28 days in female CF rats, and non-significant changes were found in most of the parameters studied such as acute experiment except significant increase in low density lipoprotein (LDL) cholesterol level at 50 and 300 mg/kg body weight, decrease in high density lipoprotein (HDL) cholesterol level at 300 mg/kg body weight, increase in SGPT activity at 50 mg/kg body weight and decrease in WBC count at 300 mg/kg body weight on 28(th) day post treatment.


Asunto(s)
Alquenos/toxicidad , Medicina Ayurvédica , Piperidinas/toxicidad , Preparaciones de Plantas/farmacología , Administración Oral , Alanina Transaminasa/biosíntesis , Alanina Transaminasa/efectos de los fármacos , Alcaloides/química , Alcaloides/toxicidad , Alquenos/química , Animales , Benzodioxoles/química , Benzodioxoles/toxicidad , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , HDL-Colesterol/antagonistas & inhibidores , HDL-Colesterol/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Evaluación Preclínica de Medicamentos , Femenino , Zingiber officinale/química , Glutatión/biosíntesis , Glutatión/efectos de los fármacos , Lipoproteínas LDL/biosíntesis , Lipoproteínas LDL/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Piper/química , Piperidinas/química , Preparaciones de Plantas/química , Alcamidas Poliinsaturadas/química , Alcamidas Poliinsaturadas/toxicidad , Ratas , Ratas Endogámicas , Factores Sexuales , Fases del Sueño , Factores de Tiempo , Pruebas de Toxicidad Aguda/métodos
18.
Planta Med ; 75(1): 59-61, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19031368

RESUMEN

Bidens pilosa is used in folk medicine for various applications due to the presence of polyacetylenes, flavonoids, terpenoids, phenylpropanoids and others. Bioactivity-guided fractionation of different extracts of B. pilosa leaf showed potential in vitro anticancer and antimalarial activity and led to the identification of a potential marker compound, phenyl-1,3,5-heptatriyne. Erythrocyte osmotic fragility experiments revealed the various extracts as well as the marker component's toxicity profiles on normal blood cells.


Asunto(s)
Alquinos/farmacología , Antimaláricos/farmacología , Antineoplásicos Fitogénicos/farmacología , Bidens/química , Medicamentos Herbarios Chinos/farmacología , Alquinos/química , Alquinos/aislamiento & purificación , Animales , Antimaláricos/química , Antimaláricos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Eritrocitos/efectos de los fármacos , Humanos , Fragilidad Osmótica/efectos de los fármacos , Hojas de la Planta/química , Plasmodium falciparum/efectos de los fármacos
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