RESUMEN
In developing countries, populations have employed herbal medicines for primary health care because they are believed to be more appropriate to the human body and have less side effects than chemically synthesized drugs. The present study aimed to develop and evaluate herbal tablets incorporated with a Thai traditional medicinal extract, U-pa-ri-waat (URW), using microwave-assisted extraction (MAE). The extraction efficiency for URW using MAE and traditional solvent extraction was compared based on the percent yield after spray drying. URW tablets were prepared using the dry granulation method. The optimized products were assessed using standard characterization methods based on the United States and British Pharmacopeias. DPPH and ABTS radical scavenging assays were performed to analyze the antioxidant capacity of the microwave-assisted extracts. The results revealed that the flowability of the dry granule with added maltodextrin was improved compared to a granule without additives, as indicated by an angle of repose of 33.69 ± 2.0°, a compressibility index of 15.38 ± 0.66, and a Hausner's ratio of 1.18 ± 0.06. The resulting formulation produced flat tablets with uniform weight variation, hardness, thickness, friability, and optimum disintegration time. The URW extracts showed antioxidant activity and MAE with maltodextrin carrier displayed the strongest DPPH and ABTS radical activities with IC50 values of 1.60 ± 0.02 µg/mL and 4.02 ± 0.24 µg/mL, respectively. The URW tablet formulation passed the quality control tests. Storage of the formulation tablets for 90 days under accelerated conditions had minimal effects on tablet characteristics.
Asunto(s)
Química Farmacéutica/métodos , Microondas , Fitoquímicos/síntesis química , Preparaciones de Plantas/síntesis química , Administración Oral , Antioxidantes/administración & dosificación , Antioxidantes/síntesis química , Antioxidantes/farmacocinética , Evaluación Preclínica de Medicamentos/métodos , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/farmacocinética , Medicina de Hierbas/métodos , Humanos , Fitoquímicos/administración & dosificación , Fitoquímicos/farmacocinética , Preparaciones de Plantas/administración & dosificación , Preparaciones de Plantas/farmacocinética , Comprimidos , TailandiaAsunto(s)
Productos Biológicos/uso terapéutico , Enfermedades Transmisibles/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Trastornos Mentales/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Preparaciones de Plantas/uso terapéutico , Productos Biológicos/síntesis química , Productos Biológicos/química , Diseño de Fármacos , Humanos , Preparaciones de Plantas/síntesis química , Preparaciones de Plantas/químicaRESUMEN
Natural products are a major pipeline for drug development and are responsible for more than 50 % of drugs on the market. NMR is a fundamental and powerful tool for the structure determination of natural products. It is essential to provide unambiguous chemical structure information on natural products in drug development research, including the structure-activity relationship, derivatization and pharmacokinetic/pharmacodynamic studies. Advancement of NMR instruments has made it possible to deal with nanomole-scale natural products for structure elucidation, but misinterpretation of NMR spectra still occurs. We review 21 natural products with revised chemical structures and the methods used for those revisions.
Asunto(s)
Descubrimiento de Drogas/métodos , Espectroscopía de Resonancia Magnética , Preparaciones de Plantas/síntesis química , Animales , Humanos , Estructura Molecular , Fitoterapia , Preparaciones de Plantas/farmacocinética , Preparaciones de Plantas/farmacología , Plantas Medicinales , Relación Estructura-ActividadRESUMEN
This work is devoted to the study and obtaining of new radioprotective agents based on natural flavonoid genistein and spherical amorphous nanoparticles (SANPs) produced from a mixture of birch bark triterpenoids. The physicochemical characteristics of the nanoparticles were studied by electron microscopy, dynamic light scattering, and UV-VIS spectroscopy. The radioprotective efficacy of the nanodrug in vivo and the possibility of its use as a radioprotective agent was shown.
Asunto(s)
Betula , Genisteína/farmacología , Nanopartículas del Metal , Fitoterapia , Preparaciones de Plantas/farmacología , Protectores contra Radiación/farmacología , Animales , Animales no Consanguíneos , Betula/química , Ésteres del Colesterol/química , Evaluación Preclínica de Medicamentos , Genisteína/síntesis química , Genisteína/química , Genisteína/toxicidad , Masculino , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Ratones , Tamaño de la Partícula , Triterpenos Pentacíclicos/química , Corteza de la Planta/química , Preparaciones de Plantas/síntesis química , Preparaciones de Plantas/química , Preparaciones de Plantas/toxicidad , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Protectores contra Radiación/síntesis química , Protectores contra Radiación/química , Protectores contra Radiación/toxicidad , Distribución Aleatoria , Análisis de Supervivencia , Resultado del Tratamiento , Triterpenos/químicaRESUMEN
The single step synthesis of a newly designed series of strigolactones (SLs) from cyclic keto enols is described. The germinating activity of these SL analogues towards seeds of the parasitic weeds Striga and Orobanche spp. is reported. The first of these SL analogues are derived from the hydroxyl γ-pyrones kojic acid and maltol, the second type from hydroxyl α-pyrones, namely, 4-hydroxy-6-methyl-2H-pyran-2-one and 4-hydroxy-coumarin and the third type from 1,3-diketones, namely, 1,3-cyclohexane-dione (dimedone) and tricyclic 1,3-dione. All keto enols are coupled in a single step with the appropriate D-ring precursor in the presence of a base to give the desired SL analogues. All SL analogues are acceptably biologically active in inducing the germination of seeds of Striga hermonthica and Orobanchecernua. Most interesting are the analogues derived from 4-hydroxy coumarin and dimedone, as they have a remarkably high biological activity towards the seeds of parasitic weeds at relatively low concentrations, comparable with that of the general standard stimulant GR24.
Asunto(s)
Germinación/efectos de los fármacos , Lactonas/síntesis química , Orobanche , Preparaciones de Plantas/síntesis química , Malezas/efectos de los fármacos , Striga , Lactonas/análisis , Lactonas/química , Lactonas/farmacología , Preparaciones de Plantas/análisis , Preparaciones de Plantas/química , Preparaciones de Plantas/farmacología , Malezas/crecimiento & desarrollo , SemillasRESUMEN
PURPOSE: To develop effective mitochondria-targeted antioxidants composed entirely of natural constituents. METHODS: Novel mitochondria-targeted antioxidants were synthesized containing plant electron carrier and antioxidant plastoquinone conjugated by nonyloxycarbonylmethyl residue with berberine or palmatine, penetrating cations of plant origin. These compounds, SkQBerb and SkQPalm, were tested in model planar phospholipid membranes and micelles, liposomes, isolated mitochondria and living cells. RESULTS: SkQBerb and SkQPalm penetrated across planar bilayer phospholipid membrane in their cationic forms and accumulated in mitochondria isolated or in living human cells in culture. Reduced forms of SkQBerb and SkQPalm as well as C10Berb and C10Palm (SkQBerb and SkQPalm analogs lacking plastoquinol moiety) revealed radical scavenging activity in lipid micelles and liposomes, while oxidized forms were inactive. In isolated mitochondria and in living cells, berberine and palmatine moieties were not reduced, so antioxidant activity of C10Berb and C10Palm was not detected. SkQBerb and SkQPalm inhibited lipid peroxidation in isolated mitochondria at nanomolar concentrations; their prooxidant effect was observed at 1,000 times higher concentrations. In human cell cuture, nanomolar SkQBerb and SkQPalm prevented fragmentation of mitochondria and apoptosis induced by exogenous hydrogen peroxide. CONCLUSION: This is the first successful attempt to construct mitochondria-targeted antioxidants composed entirely of natural components, namely plastoquinone, nonyl, acetyl and berberine or palmatine residues.
Asunto(s)
Antioxidantes/química , Alcaloides de Berberina/química , Berberina/química , Sistemas de Liberación de Medicamentos , Terapia Molecular Dirigida , Preparaciones de Plantas/síntesis química , Plastoquinona/síntesis química , Antioxidantes/metabolismo , Antioxidantes/farmacología , Berberina/metabolismo , Berberina/farmacología , Alcaloides de Berberina/metabolismo , Alcaloides de Berberina/farmacología , Composición de Medicamentos , Fibroblastos , Células HeLa , Humanos , Membrana Dobles de Lípidos/análisis , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Modelos Químicos , Fitoterapia , Preparaciones de Plantas/química , Preparaciones de Plantas/metabolismo , Preparaciones de Plantas/farmacología , Plastoquinona/análogos & derivados , Plastoquinona/química , Plastoquinona/farmacologíaRESUMEN
Four derivatives of an α,ß-amyrin mixture were synthesized by acylation with appropriate anhydrides. The structures of the compounds were confirmed by means of IR and (1)H and (13)C NMR. The compounds were screened for cytotoxic activity using four human tumor cell lines (HL-60, MDAMB-435, SF-295 and HCT-8) and normal peripheral blood mononuclear cells (PBMC). 3-O-Carboxymaleinate of α,ß-amyrin (3a/3b) were found to be the only active compounds of the series (high cytotoxicity), showing IC(50) values ranging from 1.8 to 3µM. In PBMC, 3a/3b were not toxic, suggesting selectivity for tumor cells. To better understand the mechanism of action involved in the cytotoxicity of 3a/3b, HL-60 cells treated with 3a/3b were examined for morphological changes, DNA fragmentation, cell cycle perturbation, externalization of phosphatidylserine and activation of caspases 3/7, with doxorubicin serving as the positive control. The results indicate that the cytotoxicity of 3a/3b involves the induction of cell death by apoptosis.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Burseraceae , Muerte Celular/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Ácido Oleanólico/análogos & derivados , Preparaciones de Plantas/síntesis química , Antineoplásicos/química , Caspasa 3/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Células HL-60 , Humanos , Estructura Molecular , Ácido Oleanólico/síntesis química , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Preparaciones de Plantas/análogos & derivados , Preparaciones de Plantas/farmacologíaRESUMEN
An overview is given on current efforts in drug development based on plant-derived natural products. Emphasis is on projects which have advanced to clinical development. Therapeutic areas covered include cancer, viral infections including HIV, malaria, inflammatory diseases, nociception and vaccine adjuvants, metabolic disorders, and neurodegenerative diseases. Aspects which are specific to plant-based drug discovery and development are also addressed, such as supply issues in the commercial development, and the Convention on Biological Diversity.
Asunto(s)
Diseño de Fármacos , Plantas Medicinales/química , Adyuvantes Inmunológicos/aislamiento & purificación , Adyuvantes Inmunológicos/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Analgésicos/aislamiento & purificación , Analgésicos/uso terapéutico , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/uso terapéutico , Antimaláricos/aislamiento & purificación , Antimaláricos/uso terapéutico , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/uso terapéutico , Antivirales/aislamiento & purificación , Antivirales/uso terapéutico , Fármacos Cardiovasculares/aislamiento & purificación , Fármacos Cardiovasculares/uso terapéutico , Humanos , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/uso terapéutico , Estructura Molecular , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/uso terapéutico , Preparaciones Farmacéuticas , Preparaciones de Plantas/síntesis química , Preparaciones de Plantas/química , Preparaciones de Plantas/aislamiento & purificación , Preparaciones de Plantas/uso terapéutico , Relación Estructura-ActividadRESUMEN
In this review are presented various lead compounds bearing a polyphenolic moiety and their biological targets. The relevance of these targets to develop the desired compounds as potential anti-cancer agents is discussed. For instance, caffeic acid phenethyl ester (CAPE) has preliminary been studied in our group to hold various biochemical responses. When C6 glioma cells were grown as xenografts in nude mice, treatment with CAPE (1-10 mg/kg; ip) induced a significant dose dependent decrease in tumor growth by evaluating tumor volume and tumor weight. Histochemical and immunohistochemical analysis revealed that CAPE treatment significantly reduced the number of mitotic cells and proliferating cell nuclear antigen (PCNA)-positive cells in C6 glioma. Moreover, the ability of flavonoids to scavenge free-radicals and block lipid peroxidation raises the possibility that they may act as protective factors against carcinogenesis. Furthermore, protocatechuic acid (PCA) seems to be a promising compound regarded as a candidate group for cancer preventive agents. We have isolated and investigated Hibiscus protocatechuic acid from Hibiscus sabdariffa L. Hibiscus PCA showed against oxidative damage induced by t-butyl hydroperoxide in rat primary hepatocytes, and inhibitory effect on tumor promotion in mouse skin. Finally, we review here recent progress with the analogs of natural and synthetic lead compounds in Asiatic folk medicine. Since phenolic dimmers or trimers are significantly more potent than monomer in vitro and in vivo, a large number of phenolic dimmers or trimers with linker lengths and their pharmacological properties have been investigated.
Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Antioxidantes/química , Medicina Tradicional , Preparaciones de Plantas/síntesis química , Animales , Antineoplásicos Fitogénicos/química , Antioxidantes/síntesis química , Benzofuranos/síntesis química , Benzofuranos/química , Ácidos Cafeicos/síntesis química , Ácidos Cafeicos/química , Cumarinas/síntesis química , Cumarinas/química , Asia Oriental , Flavonoides/síntesis química , Flavonoides/química , Hibiscus/química , Humanos , Ratones , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/síntesis química , Alcohol Feniletílico/química , Piper/química , Preparaciones de Plantas/química , Preparaciones de Plantas/uso terapéuticoRESUMEN
Although deoxybenzoins are intermediates in the synthesis of isoflavones, their estrogenic activity has not been investigated. Eleven deoxybenzoins were synthesized and their estrogenicity was evaluated. While their affinities for estrogen receptors (ER) ERalpha and ERbeta were found grossly comparable to those of daidzein, some exhibited considerable selectivity and transcriptional bias toward ERbeta, which appeared to allow for enhancement of ER-mediated transcription via deoxybenzoin binding of ERbeta. Their activity to stimulate the proliferation of ER-positive breast cancer cells and regulate the expression of endogenous and stably transfected reporter genes differed considerably, with some inhibiting cell proliferation while effectively inducing gene expression at the same time. Molecular modeling confirmed that deoxybenzoins fit well in the ligand binding pocket of ERbeta, albeit with different orientations. Our data support the view that deoxybenzoins constitute a promising new class of ERbeta-biased phytoestrogens.
Asunto(s)
Benzoína/análogos & derivados , Benzoína/química , Benzoína/farmacología , Isoflavonas/clasificación , Isoflavonas/farmacología , Preparaciones de Plantas/clasificación , Preparaciones de Plantas/farmacología , Receptores de Estrógenos/metabolismo , Fosfatasa Alcalina/metabolismo , Benzoína/síntesis química , División Celular/efectos de los fármacos , Línea Celular , Activación Enzimática/efectos de los fármacos , Estradiol/farmacología , Receptor alfa de Estrógeno , Receptor beta de Estrógeno , Genes Reporteros/genética , Humanos , Isoflavonas/síntesis química , Isoflavonas/química , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Fitoestrógenos , Preparaciones de Plantas/síntesis química , Preparaciones de Plantas/química , Receptores de Estrógenos/química , Relación Estructura-Actividad , Transcripción Genética/efectos de los fármacosRESUMEN
A new series of ERbeta (ERbeta) selective ligands has been prepared. One of the compounds 6, structurally related to the phytoestrogen apigenin 4, displays a binding preference for ERbeta over ERalpha of over 40-fold. In addition to its binding selectivity, 6 was able to potently induce metallothionein (an ERbeta specific response in human SAOS-2 cells) while demonstrating low potency in an ERalpha dependant ERE-tk luciferase assay in MCF-7 cells. Such receptor and cell selectivity could make 6 a useful molecular probe for better understanding the role of ERbeta in mammalian physiology.
Asunto(s)
Isoflavonas/síntesis química , Preparaciones de Plantas/síntesis química , Receptores de Estrógenos/efectos de los fármacos , Moduladores Selectivos de los Receptores de Estrógeno/síntesis química , Alquilación , Apigenina , Línea Celular , Receptor alfa de Estrógeno , Receptor beta de Estrógeno , Flavonoides/química , Flavonoides/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Genisteína/síntesis química , Genisteína/farmacología , Humanos , Indicadores y Reactivos , Isoflavonas/química , Isoflavonas/farmacología , Ligandos , Luciferasas/genética , Metalotioneína/biosíntesis , Fitoestrógenos , Preparaciones de Plantas/química , Preparaciones de Plantas/farmacología , Receptores de Estrógenos/biosíntesis , Receptores de Estrógenos/genética , Moduladores Selectivos de los Receptores de Estrógeno/química , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Relación Estructura-ActividadRESUMEN
Artemisinin, a sesquiterpene lactone containing an endoperoxide bridge, has been isolated from the aerial parts of Artemisia annua L. plants. It is effective against both drug-resistant and cerebral malaria-causing strains of Plasmodium falciparum. The relatively low yield (0.01-0.8 %) of artemisinin in A. annua is a serious limitation to the commercialization of the drug. Therefore, the enhanced production of artemisinin either in cell/tissue culture or in the whole plant of A. annua is highly desirable. It can be achieved by a better understanding of the biochemical pathway leading to the synthesis of artemisinin and its regulation by both exogenous and endogenous factors. Furthermore, genetic engineering tools can be employed to overexpress gene(s) coding for enzyme(s) associated with the rate limiting step(s) of artemisinin biosynthesis or to inhibit the enzyme(s) of other pathway competing for its precursors. These aspects which may be employed to enhance the yield of artemisinin both in vitro and in vivo are discussed in this review.