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2.
Sci Rep ; 14(1): 51, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167521

RESUMO

Suspect screening and untargeted analysis using UHPLC-qToF are two advanced analytical approaches now used to achieve an extensive chemical profile of samples, which are then typically confirmed through targeted analysis. These techniques can detect a large number of chemical features simultaneously and are currently being introduced into the study of contaminants of emerging concern (CECs) and into the study of the extent of human chemical exposure (the exposome). Here is described the use of these techniques to characterize chemical mixtures derived from the OECD 301F ready biodegradability test (RBT) of a chemical and natural formulation currently used to treat reflux disease and functional dyspepsia. Untargeted analysis clearly evidenced a different behavior between formulations containing only natural products with respect to that containing synthetic and non-naturally occurring substances. Suspect screening analysis improved the untargeted analysis of the omeprazole-based medicine, leading to the tentative identification of a number of omeprazole-derived transformation products, thereby enabling their preliminary quali-quantitative evaluation. Targeted analysis was then performed to confirm the preliminary data gained from the suspect screening approach. The validation of the analytical method for the quantitative determination of omeprazole and its major metabolite, omeprazole sulphide, has provided robust data to evaluate the behavior of omeprazole during the OECD 301F test. Using advanced analytical approaches, the RBT performed on the two products under investigation confirmed that omeprazole is not readily biodegradable, while the medical device made of natural substances has proven to be readily biodegradable.


Assuntos
Refluxo Gastroesofágico , Inibidores da Bomba de Prótons , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Omeprazol , Personalidade
3.
Phytochemistry ; 215: 113790, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37487919

RESUMO

Natural complex substances (NCSs) are a heterogeneous family of substances that are notably used as ingredients in several products classified as food supplements, medical devices, cosmetics and traditional medicines, according to the correspondent regulatory framework. The compositions of NCSs vary widely and hundreds to thousands of compounds can be present at the same time. A key concept is that NCSs are much more than the simple sum of the compounds that constitute them, in fact some emerging phenomena are the result of the supramolecular interaction of the constituents of the system. Therefore, close attention should be paid to produce and characterize these systems. Today many natural compounds are produced by chemical synthesis and are intentionally added to NCSs, or to formulated natural products, to enhance their properties, lowering their production costs. Market analysis shows a tendency of people to use products made with NCSs and, currently, products made with ingredients of natural origin only are not conveniently distinguishable from those containing compounds of synthetic origin. Furthermore, the uncertainty of the current European regulatory framework does not allow consumers to correctly differentiate and identify products containing only ingredients of natural origin. The high demand for specific and effective NCSs and their high-cost offer on the market, create the conditions to economically motivated sophistications, characterized by the addition of a cheap material to a more expensive one, just to increase profit. This type of practice can concern both the addition of less valuable natural materials and the addition of pure artificial compounds with the same structure as those naturally present. In this scenario, it becomes essential for producers of natural products to have advanced analytical techniques to evaluate the effective naturalness of NCSs. In fact, synthetically obtained compounds are not identical to their naturally occurring counterparts, due to the isotopic composition or chirality, as well as the presence of different trace metabolites (since pure substances in nature do not exist). For this reason, in this review, the main analytical tests that can be performed to differentiate natural compounds from their synthetic counterparts will be highlighted and the main analytical technologies will be described. At the same time, the main fingerprint techniques useful for characterizing the complexity of the NCSs, also allowing their identification and quali-quantitative evaluation, will be described. Furthermore, NCSs can be produced through different manufacturing processes, not all of which are on the same level of quality. In this review the most suitable technologies for green processes that operate according to physical extraction principles will be presented, as according to the authors they are the ones that come closest to creating more life-cycle compatible NCSs and that are well suited to the European green deal, a strategy with the aim of transforming the EU into a sustainable and resource-efficient society by 2050.


Assuntos
Produtos Biológicos , Humanos
4.
J Mass Spectrom ; 58(10): e4924, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37365837

RESUMO

Drugs are indispensable products with incontrovertible benefits to human health and lifestyle. However, due to their overuse and improper disposal, unwanted residues of active pharmaceutical ingredients (APIs) have been found in different compartments of the environment and now are considered as contaminants of emerging concern (CECs). Therefore, they are very likely to have a boomerang effect on human health, because they can enter into the food cycle. In the current legislation framework, one of the tests first used to evaluate biodegradation of APIs as well as chemical compounds is the ready biodegradability test (RBT). This test can be performed according to a series of protocols prepared by Organization for Economic Co-operation and Development (OECD) and usually is carried out on pure compounds. RBTs, largely used due to their relatively low cost, perceived standardization, and straightforward implementation and interpretation, are known to have a number of well-documented limitations. In this work, following a recently reported approach, we propose to improve the evaluation of the RBT results applying advanced analytical techniques based on mass spectrometry, not only to the APIs but also to complex formulated products, as the biodegradability can potentially be affected by the formulation. We evaluated the ready biodegradability of two therapeutic products, Product A-a drug based on Metformin-and Product B-Metarecod a natural substance-based medical device-through the acquisition of the fingerprint by ultra-high-performance chromatograph coupled to a quadrupole time of flight (UHPLC-qToF) of samples coming from the RBT OECD 301F. Untargeted and targeted evaluation confirmed the different behavior of the two products during the respirometry-manometric test, which showed a difficulty of the Metformin-based drug to come back in the life cycle, whereas Metarecod resulted ready biodegradable. The positive results of this research will hopefully be useful in the future for a better evaluation of the risk/benefit ratio of APIs extended to the environment.


Assuntos
Metformina , Humanos , Metformina/metabolismo , Cromatografia Líquida de Alta Pressão , Biodegradação Ambiental , Espectrometria de Massas
5.
Mass Spectrom Rev ; 42(4): 1358-1396, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35238411

RESUMO

Metabolomics is an area of intriguing and growing interest. Since the late 1990s, when the first Omic applications appeared to study metabolite's pool ("metabolome"), to understand new aspects of the global regulation of cellular metabolism in biology, there have been many evolutions. Currently, there are many applications in different fields such as clinical, medical, agricultural, and food. In our opinion, it is clear that developments in metabolomics analysis have also been driven by advances in mass spectrometry (MS) technology. As natural complex products (NCPs) are increasingly used around the world as medicines, food supplements, and substance-based medical devices, their analysis using metabolomic approaches will help to bring more and more rigor to scientific studies and industrial production monitoring. This review is intended to emphasize the importance of metabolomics as a powerful tool for studying NCPs, by which significant advantages can be obtained in terms of elucidation of their composition, biological effects, and quality control. The different approaches of metabolomic analysis, the main and basic techniques of multivariate statistical analysis are also briefly illustrated, to allow an overview of the workflow associated with the metabolomic studies of NCPs. Therefore, various articles and reviews are illustrated and commented as examples of the application of MS-based metabolomics to NCPs.


Assuntos
Metaboloma , Metabolômica , Metabolômica/métodos , Espectrometria de Massas/métodos , Análise Multivariada , Controle de Qualidade
6.
J Mass Spectrom ; 57(8): e4878, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36065819

RESUMO

The evolution of the regulatory framework for medical devices in the EU (Reg 2017/745) has opened the study of complex systems emerging properties. This makes necessary to identify new analytical approaches able of characterizing complex natural substrates as completely as possible. Therefore, omics approaches and advanced analytical methods for the determination of metabolite classes appear to be at the forefront to meet this need. In this perspective, a new approach based on the suspect screening was developed to detect gallotannins. Gallotannins are a class of phenols with a polymeric nature; thus, there are no pure analytical standards available for all possible structures and their quali-quantitative determination in complex natural substrates can be a challenge. A new UHPLC-qToF method was developed and used to create an "in-house tannin database" with a dual purpose: (1) as a classic list of suspects and (2) to identify core fragments common to gallotannins to have another list of putative suspects based on the common fragment. The method was validated. The application of the method to a "system of molecules" extracted from the leaves of Hamamelis virginiana L. (Witch-hazel) allowed to the characterization of a total of 29 phenols by a suspect screening approach. Therefore, 15 gallotannins were putatively annotated while another 3 were confidently identified. All the gallotannins were semiquantified according to external regression curves of gallic acid and hamamelitannin based on core fragments at m/z 125.0244 and m/z 169.0142, the building blocks of the polymers. This new method provides a practical fit-to-purpose approach for the quali-quantitative screening evaluation of gallotannins, useful for creating multivariate control charts applicable in process development of complex natural systems or in quality control. The approach is innovative, and after specific checks, it can in principle be suitable for metabolomic fingerprint analysis of gallotannins among witch-hazel extract (WHE) samples.


Assuntos
Hamamelis , Taninos Hidrolisáveis , Cromatografia Líquida de Alta Pressão/métodos , Hamamelis/química , Taninos Hidrolisáveis/química , Metabolômica , Fenóis/química
7.
Front Nutr ; 9: 887378, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118773

RESUMO

Experimental evidence suggests that neuroinflammation is a key pathological event of many diseases affecting the nervous system. It has been well recognized that these devastating illnesses (e.g., Alzheimer's, Parkinson's, depression, and chronic pain) are multifactorial, involving many pathogenic mechanisms, reason why pharmacological treatments are unsatisfactory. The purpose of this study was to evaluate the efficacy of a vegetal mixture capable of offering a multiple approach required to manage the multifactoriality of neuroinflammation. A mixture composed of Zingiber officinale (150 mg kg-1), Echinacea purpurea (20 mg kg-1), and Centella asiatica (200 mg kg-1) was tested in a mouse model of systemic neuroinflammation induced by lipopolysaccharide (LPS, 1 mg kg-1). Repeated treatment with the vegetal mixture was able to completely counteract thermal and mechanical allodynia as reported by the Cold plate and von Frey tests, respectively, and to reduce the motor impairments as demonstrated by the Rota rod test. Moreover, the mixture was capable of neutralizing the memory loss in the Passive avoidance test and reducing depressive-like behavior in the Porsolt test, while no efficacy was shown in decreasing anhedonia as demonstrated by the Sucrose preference test. Finally, LPS stimulation caused a significant increase in the activation of glial cells, of the central complement proteins and of inflammatory cytokines in selected regions of the central nervous system (CNS), which were rebalanced in animals treated with the vegetal mixture. In conclusion, the vegetal mixture tested thwarted the plethora of symptoms evoked by LPS, thus being a potential candidate for future investigations in the context of neuroinflammation.

8.
Nutrients ; 12(6)2020 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-32486519

RESUMO

Current pharmacological therapies for the management of chronic articular diseases are far from being satisfactory, so new strategies need to be investigated. We tested the intra-articular pain relieving properties of a system of molecules from a characterized Centella asiatica extract (14G1862) in a rat model of osteoarthritis induced by monoiodoacetate (MIA). 14G1862 (0.2-2 mg mL-1) was intra-articularly (i.a.) injected 7 days after MIA, behavioural and histological evaluations were performed 14, 30 and 60 days after treatments. Moreover, the effect of 14G1862 on nitrate production and iNOS expression in RAW 264.7 macrophages stimulated with LPS was assessed. In vitro, 14G1862 treatment attenuated LPS-induced NO production and iNOS expression in a comparable manner to celecoxib. In vivo, 14G1862 significantly reduced mechanical allodynia and hyperalgesia, spontaneous pain and motor alterations starting on day 14 up to day 60. The efficacy was higher or comparable to that evoked by triamcinolone acetonide (100 µg i.a.) used as reference drug. Histological evaluation highlighted the improvement of several morphological parameters in MIA + 14G1862-treated animals with particularly benefic effects on joint space and fibrin deposition. In conclusion, i.a. treatment with Centella asiatica is a candidate to be a novel effective approach for osteoarthritis therapy.


Assuntos
Analgésicos/uso terapêutico , Centella/química , Injeções Intra-Articulares/métodos , Dor/tratamento farmacológico , Triterpenos/uso terapêutico , Analgésicos/farmacologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Ácido Iodoacético , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Nitratos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Manejo da Dor , Extratos Vegetais , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Triterpenos/farmacologia
9.
J Mass Spectrom ; 55(7): e4459, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31663260

RESUMO

Considering the high complexity of natural extracts, because of the presence of organic molecules of different chemical nature, the possibility of formation of noncovalent complexes should be taken into account. In a previous investigation, the formation of bimolecular complexes between caffeine and catechins in green tea extracts (GTE) has been experimentally proven by means of mass spectrometric and 1 H nuclear magnetic resonance experiments. The same approaches have been employed in the present study to evaluate the presence of bimolecular complexes in Ceylon tea and mate extracts. The obtained results show that in the case of Ceylon tea extracts, protonated theaflavin is detectable, together with theaflavin/caffein complexes, while caffeine/catechin complexes, already detected in green tea, are still present but at lower concentration. This aspect is evidenced by the comparison of precursor ion scans performed on protonated caffeine for the two extracts. The spectra obtained in these conditions for GTE and Ceylon tea show that the complexes of caffeine with epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG), highy abundant in the case of GTE (signal-to-chemical noise ratio in the range 50-100), are negligible (signal-to-chemical noise ratio in the range 2-3) in the case of Ceylon tea. Mate extracts show the formation of bimolecular complexes involving caffeine but not catechins, and chlorogenic acid becomes responsible for other complex formation. Under positive ion and negative ion conditions, accurate mass measurements allow the identification of malealdehyde, chlorogenic acid, caffeine, two isomers of dicaffeoylquinic acid, rutin, and kaempferol-3-O-rutinoside. These data indicate that the formation of complexes in natural extracts is a common behavior, and their presence must be considered in the description of natural extracts and, consequently, in their biological activity.


Assuntos
Camellia sinensis/química , Ilex paraguariensis/química , Espectrometria de Massas/métodos , Extratos Vegetais/química , Chá/química , Biflavonoides/análise , Cafeína/análise , Catequina/análogos & derivados , Catequina/análise , Ácido Clorogênico/análise , Cromatografia Líquida , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem/métodos
10.
J Nat Prod ; 81(11): 2338-2347, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30372064

RESUMO

A hypothesis on the peculiar pharmacological behavior of biologically active natural compounds is based on the occurrence of molecular interactions originating from the high complexity of the natural matrix, following the rules of supramolecular chemistry. In this context, some investigations were performed to establish unequivocally the presence of caffeine/catechin complexes in green tea extracts (GTEs). 1H NMR spectroscopy was utilized to compare profiles from GTEs with caffeine/catechin mixtures in different molar ratios, showing that peaks related to caffeine in GTEs are generally upfield shifted compared to those of free caffeine. On the other hand, ESIMS experiments performed on GTE, by means of precursor ion scan and neutral loss scan experiments, proved unequivocally the presence of caffeine/catechin complexes. Further investigations were performed by an LC-MS method operating at high-resolution conditions. The reconstructed ion chromatograms of the exact mass ions corresponding to caffeine/catechin species have been obtained, showing the presence of complexes of caffeine with gallate-type catechins. Furthermore, this last approach evidenced the presence of the same complex with different structures, consequently exhibiting different retention times. Both MSE and product ion MS/MS methods confirm the nature of caffeine/catechin complexes of the detected ions, showing the formation of protonated caffeine.


Assuntos
Cafeína/análise , Camellia sinensis/química , Catequina/análise , Extratos Vegetais/química , Cafeína/química , Catequina/química , Cromatografia Líquida , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray
11.
Sci Rep ; 8(1): 14364, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30254294

RESUMO

Oxaliplatin treatment is associated with the development of a dose-limiting painful neuropathy impairing patient's quality of life. Since oxidative unbalance is a relevant mechanism of oxaliplatin neurotoxicity, we assessed the potential antioxidant properties of Vitis vinifera extract in reducing oxaliplatin-induced neuropathy as a valuable therapeutic opportunity. A hydroalcoholic extract of Vitis vinifera red leaf was characterized and tested in primary rat astrocyte cells treated with oxaliplatin (100 µM). Oxaliplatin lethality in the human adenocarcinoma cell line HT-29 was evaluated in the absence and presence of the extract. In vivo, pain hypersensitivity was measured in a rat model of neuropathy induced by oxaliplatin and ex vivo molecular targets of redox balance were studied. Vitis vinifera extract (50 µg mL-1, 4 h incubation) significantly reduced the oxaliplatin-dependent superoxide anion increase and lipid peroxidation in rat astrocytes but did not interfere with the mortality elicited by oxaliplatin in HT-29 cancer cells. In oxaliplatin-treated rats, a repeated daily administration of the Vitis vinifera extract (300 mg kg-1, p.o.) significantly prevented mechanical and thermal hypersensitivity to noxious and non noxious stimuli. mRNA and protein levels of Nrf2 were normalized in spinal cord and DRGs. Moreover, in the spinal cord, the extract significantly decreased the activation of astrocytes. Vitis vinifera reduced oxidative damages and relieved pain without influencing oxaliplatin anti-cancer activity.


Assuntos
Álcoois/química , Antioxidantes/farmacologia , Neurotoxinas/toxicidade , Oxaliplatina/toxicidade , Extratos Vegetais/farmacologia , Vitis/química , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Células HT29 , Humanos , NAD(P)H Desidrogenase (Quinona)/genética , NADPH Desidrogenase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Folhas de Planta/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Medula Espinal/citologia
12.
Z Naturforsch C J Biosci ; 72(5-6): 219-226, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28160544

RESUMO

Hypericum perforatum L. has been used for centuries as a natural remedy for the treatment of many disorders. Neuropathic pain is a common side effect of oxaliplatin-based chemotherapy and often the cause of therapy discontinuation. Thanks to its anti-inflammatory and analgesic effects, the use of H. perforatum may be a novel therapeutic strategy for neuropathy. The aim of this paper was to evaluate the effect of H. perforatum hydrophilic extract on an in vitro model of oxaliplatin-induced neurotoxicity. The antioxidant potential of extract was first evaluated in cell-free models by the thiobarbituric acid-reactive substances assay and nitro blue tetrazolium oxidation test; the ability of H. perforatum extract to reduce oxaliplatin-induced caspase-3 activity in rat astrocytes and its potential interference with the cytotoxic effects of oxaliplatin in a colorectal cancer in vitro model (HT-29 cells) were also evaluated. The extract showed a significant antioxidant effect and was able to reduce caspase-3 activity in rat astrocytes. Of note, the extract alone exerted a cytotoxic effect in HT-29 cells and did not reduce the cytotoxicity of oxaliplatin in HT-29 cells. These data suggest that H. perforatum could be used as a novel therapeutic strategy for counteracting chemotherapy-induced neuropathy.


Assuntos
Antineoplásicos/toxicidade , Astrócitos/efeitos dos fármacos , Hypericum/química , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/prevenção & controle , Compostos Organoplatínicos/toxicidade , Extratos Vegetais/farmacologia , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Astrócitos/metabolismo , Astrócitos/patologia , Caspase 3/metabolismo , Citoproteção , Células HT29 , Humanos , Fármacos Neuroprotetores/isolamento & purificação , Síndromes Neurotóxicas/etiologia , Oxaliplatina , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos
13.
J Vasc Res ; 53(5-6): 255-268, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27923233

RESUMO

Lymphatic leakage can be seen as a detrimental phenomenon associated with fluid retention and deposition as well as gain of weight. Moreover, lymphatic dysfunction is associated with an inflammatory environment and can be a substrate for other health conditions. A number of treatments can ameliorate lymphatic vasculature: natural substances have been used as treatment options particularly suitable for their consolidated effectiveness and safety profile. Here we report the protective effect of AdipoDren®, an association of a series of plant-derived natural complexes, on lymphatic endothelium permeability promoted by interleukin-1 beta (IL-1ß) and the associated molecular mechanisms. AdipoDren® demonstrated a protective effect on dermal lymphatic endothelial cell permeability increased by IL-1ß. Reduced permeability was due to the maintenance of tight junctions and cell-cell localisation of occludin and zonula occludens-1 (ZO-1). Moreover, AdipoDren® reduced the expression of the inflammatory key element cyclooxygenase-2 (COX-2), while not altering the levels of endothelial and inducible nitric oxide synthases (eNOS and iNOS). The upregulation of antioxidant enzymatic systems (catalase and superoxide dismutase-1, SOD-1) and the downregulation of pro-oxidant markers (p22 phox subunit of NADPH oxidase) were also evident. In conclusion, AdipoDren® would be useful to ameliorate conditions of altered lymphatic vasculature and to support the physiological functionality of the lymphatic endothelium.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Endotélio Linfático/efeitos dos fármacos , Interleucina-1beta/farmacologia , Linfedema/tratamento farmacológico , Extratos Vegetais/farmacologia , Preparações de Plantas/farmacologia , Junções Íntimas/efeitos dos fármacos , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Endotélio Linfático/metabolismo , Endotélio Linfático/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Humanos , Linfedema/metabolismo , Linfedema/fisiopatologia , NADPH Oxidases/metabolismo , Ocludina/metabolismo , Rutina/farmacologia , Superóxido Dismutase-1/metabolismo , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
14.
Phytomedicine ; 22(7-8): 752-8, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-26141762

RESUMO

BACKGROUND: Tanacetum parthenium L., commonly called Feverfew, is known for anti-inflammatory and anti-migraine properties. PURPOSE: Aimed to individuate new therapeutical strategies to control acute and persistent pain induced by different origins we tested two hydroalcoholic extracts obtained from Feverfew flowers and leaves, respectively. STUDY DESIGN: Extracts were characterized according to the European Pharmacopoeia monograph. Both the extracts were tested after acute per os administration in the dose range 30-1000 mg kg(-1). The anti-nociceptive properties were evaluated by the Writhing test in mice. RESULTS: The number of abdominal contractions was dose dependently reduced by the flower extract. It reduced mechanical hypersensitivity (Paw pressure test) related to the acute inflammatory phase induced by carrageenan similarly to diclofenac and ibuprofen. In the osteoarthritis model induced by intra articular injection of monoiodoacetate (MIA) the flower extract significantly increased the pain threshold peaking 30 min after treatment. Moreover, it was effective in the chronic constriction injury model of neuropathic pain showing activity similar to the anti-epileptic drug gabapentin. The flower extract activity was confirmed in rat models of chemotherapy-induced neuropathic pain. The mechanical hypersensitivity induced by repeated treatments with the anticancer drug oxaliplatin and with the antiviral dideoxycytidine was significantly reduced after a single injection of Feverfew flower extract. The leaf extract showed lesser efficacy and potency and it was devoid of any effect in carrageenan-, MIA- and chemotherapy-induced pain. CONCLUSION: The present Feverfew flower extract behaves as a potent pain reliever in acute, inflammatory, articular and neuropathic pain. It appears as a natural strategy potentially suitable for the treatment of different kinds of pain.


Assuntos
Analgésicos/farmacologia , Flores/química , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Tanacetum parthenium/química , Animais , Anti-Inflamatórios/farmacologia , Masculino , Camundongos , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley
15.
Oncotarget ; 6(20): 18134-50, 2015 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-26136339

RESUMO

Malignant pleural mesothelioma is a poorly treated neoplasia arising from the pleural mesothelial lining. Here we document that the leaf extract of Cynara scolymus exerts broad antitumoral effects both in vitro and in vivo on mesothelioma cell lines. We found that Cynara scolymus treatment affects strongly cell growth, migration and tumor engraftment of mesothelioma cell lines. Strikingly, dietary feeding with Cynara scolymus leaf extract reduces the growth of mesothelioma xenografted tumors similarly to pemetrexed, a commonly employed drug in the treatment of mesothelioma. In aggregate our findings suggest that leaf extract of Cynara scolymus holds therapeutic potential for the treatment of mesothelioma.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Cynara scolymus , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Extratos Vegetais/farmacologia , Neoplasias Pleurais/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cynara scolymus/química , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mesotelioma/metabolismo , Mesotelioma/patologia , Mesotelioma Maligno , Camundongos , Invasividade Neoplásica , Fitoterapia , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Plantas Medicinais , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Nat Prod Commun ; 9(4): 565-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24868885

RESUMO

The availability of reliable herbal formulations is essential in order to assure the maximal activity and to limit unwanted side-effects. The correct concentration of declared components of herbal products is a matter of health legislation and regulation, but is still a topic under debate in the field of quality control assessment. In the present work specific constituents of artichoke leaf extracts, considered as a test herbal product, were measured by standard spectrophotometric and HPLC methods (for quantitative determination of some components only), and results were correlated with the ESI-MS (showing the full metabolomic fingerprint). Phytocomplex stability over time was also investigated in batches submitted to different storage conditions. The results indicated excellent agreement between the two approaches in the measurement of total caffeoylquinic acids and chlorogenic acid contents, but the metabolomic ESI-MS method approach provides a more complete evaluation and monitoring of the composition of a herbal product, without focusing only on a single/few compound measurements. Therefore, the ESI-MS method can be proposed for the evaluation of the quality of complex matrices, such as those in a phytocomplex. Another aspect lies in the possibility to obtain a broad-spectrum stability control of herbal formulations, requiring minimal sample pre-processing procedures.


Assuntos
Cynara scolymus/química , Cynara scolymus/metabolismo , Mapeamento de Peptídeos/métodos , Folhas de Planta/química , Folhas de Planta/metabolismo , Metabolômica
17.
Fitoterapia ; 92: 23-33, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24125916

RESUMO

Painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes and the few approved therapies for the management of pain have limited efficacy and side effects. With the aim to explore and develop new pharmacological treatments, we investigated the antihyperalgesic properties of St. John's Wort (SJW) and feverfew in streptozotocin (STZ)-diabetic rats. Acute administration of a SJW seed extract reversed mechanical hyperalgesia with a prolonged effect. A SJW extract obtained from the aerial portion of the plant and a feverfew flower extract partially relieved neuropathic pain whereas a feverfew leaf extract was ineffective. The antihyperalgesic efficacy of these herbal drugs was comparable to that of clinically used antihyperalgesic drugs (carbamazepine, lamotrigine, l-acetyl-levocarnitine). Further examinations of SJW and feverfew composition revealed that hyperforin and hypericin might be responsible for the antihyperalgesic properties of SJW whereas the efficacy of feverfew seems to be related to the presence of parthenolide. Rats undergoing treatment with SJW and feverfew did not show any behavioral side effect or sign of altered locomotor activity. Our results suggest that SJW and feverfew extracts may become new therapeutic perspectives for painful DPN.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Hypericum/química , Fitoterapia , Extratos Vegetais/uso terapêutico , Tanacetum parthenium/química , Animais , Antracenos , Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/complicações , Flores/química , Hiperalgesia/etiologia , Perileno/análogos & derivados , Perileno/farmacologia , Perileno/uso terapêutico , Floroglucinol/análogos & derivados , Floroglucinol/farmacologia , Floroglucinol/uso terapêutico , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Ratos , Sementes/química , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Terpenos/farmacologia , Terpenos/uso terapêutico
18.
J Mass Spectrom ; 48(10): 1078-82, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24130010

RESUMO

Pyrrolizidine alkaloids (PAs) are complex molecules, present in plants as free bases and N-oxides. They are known for their hepatotoxicity, and consequently there is a health risk associated with the use of medicinal herbs that contain PAs. Unfortunately, there is no international regulation of PAs in foods, unlike those for herbs and medicines: in particular, for herbal preparation or herbal extracts, the total PA content must not exceed 1 µg/kg or 1 µg/l, respectively. Borago officinalis seed oil is a source of γ-linolenic acid, and its use is increased in both pharmaceutical and health food industries. Even if studies based on gas chromatography and TLC methods showed that PAs are not co-extracted with oil, the development of a rapid and sensitive method able to evaluate the presence of PAs in commercially available products is surely of interest. The presence of PAs in a commercially available Borago officinalis seed oil was tested either in the oil sample diluted with tetrahydrofuran/methanol (MeOH)/H2 O (85/10/5 v:v:v) or after extraction with MeOH/H2 O (50/50 v:v) solution The samples were analysed by electrospray ionization in positive ion mode and in high mass resolution (60,000) conditions. In both cases to evaluate the effectiveness of the method, spiking experiments were performed adding known amount of two PA standards to the borage seed oil. A limit of detection in the order of 200 ppt was determined for these two compounds, strongly analogous to Borago officinalis seed oil PAs. Consequently, if present, PAs level in Borago officinalis seed oil must lower than 200 ppt.


Assuntos
Borago/química , Óleos de Plantas/química , Alcaloides de Pirrolizidina/análise , Sementes/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Limite de Detecção , Espectrometria de Massas por Ionização por Electrospray/economia , Espectrometria de Massas em Tandem/economia , Espectrometria de Massas em Tandem/métodos
19.
J AOAC Int ; 92(3): 797-805, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19610370

RESUMO

Botanical extracts are standardized to > or = 1 marker compounds (MCs). This standardization provides a certain level of quality control, but not complete quality assurance. Thus, industries are looking for other satisfactory systems to improve standardization. This study focuses on the standardization of herbal medicines by combining 2 parameters: the concentration of the MC and antioxidant capacity. Antioxidant capacity was determined with the oxygen radical absorbance capacity (ORAC) method and the concentrations of the MCs, by high-performance liquid chromatography. Total phenols were also determined by the Folin-Ciocolteau method. The ORAC values, expressed as micromol Trolox equivalents/100 g (ORAC %), of 12 commercial herbal extracts were related to the ORAC values of the respective pure MCs at the concentrations at which the MCs occur in products (ORAC-MC %). The ORAC % values of 11 extracts were higher than those of the respective MCs and the ratios ORAC-MC %/ORAC % ranged from 0.007 to 0.7, whereas in the case of Olea europaea leaves, the same ratio was 1.36. The ORAC parameters and their ratios, as well as the linear relationship between ORAC-MC % and ORAC %, are described and discussed as tools for improving the standardization of herbal products and detecting modifications due to herb processing and storage.


Assuntos
Antioxidantes/análise , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/normas , Liofilização , Fenóis/análise , Extratos Vegetais/análise
20.
J Agric Food Chem ; 53(26): 9860-6, 2005 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-16366666

RESUMO

Immature bitter orange fruit and its extracts have been introduced into the market as an alternative to Ephedra in weight loss products. However, the safety of the immature bitter orange fruit and its extracts is a debated argument due to the presence of synephrine, a constituent known as a sympathomimetic agent. In this paper, we describe the development of a new, rapid, and simple liquid chromatography-electrospray ionization-tandem mass spectrometry method devoted to the quantitative determination of synephrine in bitter orange samples, containing a high quantity of synephrine, and sweet orange samples, known to contain a low level of synephrine but at the same time being one of the main synephrine sources in a normal human diet. Two bitter orange dry extracts containing 5 and 6% sSynephrine and 10 sweet orange samples have been analyzed. Between the sweet orange samples, six were fresh oranges and four were fresh-squeezed juices; in these samples, the synephrine levels ranged from 0.00128 to 0.00349%.


Assuntos
Citrus/química , Sinefrina/análise , Bebidas/análise , Calibragem , Cromatografia Líquida , Extratos Vegetais/análise , Padrões de Referência , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta
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