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1.
J Nat Prod ; 86(9): 2228-2237, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37638654

RESUMO

Given that the essence of Science is a search for the truth, one might expect that those identifying as scientists would be conscientious and observant of the demands this places on them. However, that expectation is not fulfilled universally as, not too surprisingly, egregious examples of unethical behavior appear and are driven by money, personal ambition, performance pressure, and other incentives. The reproducibility-, fact-, and truth-oriented modus operandi of Science has come to face a variety of challenges. Organized into 11 cases, this article outlines examples of compromised integrity from borderline to blatant unethical behavior that disgrace our profession unnecessarily. Considering technological developments in neural networks/artificial intelligence, a host of factors are identified as impacting Good Ethical Practices. The goal is manifold: to raise awareness and offer perspectives for refocusing on Science and true scientific evidence; to trigger discussion and developments that strengthen ethical behavior; to foster the recognition of the beauty, simplicity, and rewarding nature of scientific integrity; and to highlight the originality of intelligence.


Assuntos
Produtos Biológicos , Inteligência Artificial , Reprodutibilidade dos Testes , Editoração , Redes Neurais de Computação
2.
J Nat Prod ; 86(2): 460-472, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36716213

RESUMO

Botanical ingredients are used widely in phytomedicines, dietary/food supplements, functional foods, and cosmetics. Products containing botanical ingredients are popular among many consumers and, in the case of herbal medicines, health professionals worldwide. Government regulatory agencies have set standards (collectively referred to as current Good Manufacturing Practices, cGMPs) with which suppliers and manufacturers must comply. One of the basic requirements is the need to establish the proper identity of crude botanicals in whole, cut, or powdered form, as well as botanical extracts and essential oils. Despite the legal obligation to ensure their authenticity, published reports show that a portion of these botanical ingredients and products are adulterated. Most often, such adulteration is carried out for financial gain, where ingredients are intentionally substituted, diluted, or "fortified" with undisclosed lower-cost ingredients. While some of the adulteration is easily detected with simple laboratory assays, the adulterators frequently use sophisticated schemes to mimic the visual aspects and chemical composition of the labeled botanical ingredient in order to deceive the analytical methods that are used for authentication. This review surveys the commonly used approaches for botanical ingredient adulteration and discusses appropriate test methods for the detection of fraud based on publications by the ABC-AHP-NCNPR Botanical Adulterants Prevention Program, a large-scale international program to inform various stakeholders about ingredient and product adulteration. Botanical ingredients at risk of adulteration include, but are not limited to, the essential oils of lavender (Lavandula angustifolia, Lamiaceae), rose (Rosa damascena, Rosaceae), sandalwood (Santalum album, Santalaceae), and tea tree (Melaleuca alternifolia, Myrtaceae), plus the extracts of bilberry (Vaccinium myrtillus, Ericaceae) fruit, cranberry (Vaccinium macrocarpon, Ericaceae) fruit, elder (Sambucus nigra, Viburnaceae) berry, eleuthero (Eleutherococcus senticosus, Araliaceae) root, ginkgo (Ginkgo biloba, Ginkgoaceae) leaf, grape (Vitis vinifera, Vitaceae) seed, saw palmetto (Serenoa repens, Arecaceae) fruit, St. John's wort (Hypericum perforatum, Hypericaceae) herb, and turmeric (Curcuma longa, Zingiberaceae) root/rhizome, among numerous others.


Assuntos
Ingredientes de Alimentos , Óleos Voláteis , Plantas Medicinais , Plantas Medicinais/química , Suplementos Nutricionais
3.
Regul Toxicol Pharmacol ; 144: 105471, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37604297

RESUMO

Interest in botanicals, particularly as dietary supplement ingredients, is growing steadily. This growth, and the marketing of new ingredients and combination products as botanical dietary supplements, underscores the public health need for a better understanding of potential toxicities associated with use of these products. This article and accompanying template outline the resources to collect literature and relevant information to support the design of botanical toxicity studies. These resources provide critical information related to botanical identification, characterization, pre-clinical and clinical data, including adverse effects and interactions with pharmaceuticals. Toxicologists using these resources should collaborate with pharmacognosists and/or analytical chemists to enhance knowledge of the botanical material being tested. Overall, this guide and resource list is meant to help locate relevant information that can be leveraged to inform on decisions related to toxicity testing of botanicals, including the design of higher quality toxicological studies.


Assuntos
Suplementos Nutricionais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Suplementos Nutricionais/toxicidade
4.
Regul Toxicol Pharmacol ; 128: 105090, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34863907

RESUMO

Botanical dietary supplement use is widespread and growing, therefore, ensuring the safety of botanical products is a public health priority. This commentary describes the mission and objectives of the Botanical Safety Consortium (BSC) - a public-private partnership aimed at enhancing the toolkit for conducting the safety evaluation of botanicals. This partnership is the result of a Memorandum of Understanding between the US FDA, the National Institute of Environmental Health Sciences, and the Health and Environmental Sciences Institute. The BSC serves as a global forum for scientists from government, academia, consumer health groups, industry, and non-profit organizations to work collaboratively on adapting and integrating new approach methodologies (NAMs) into routine botanical safety assessments. The objectives of the BSC are to: 1) engage with a group of global stakeholders to leverage scientific safety approaches; 2) establish appropriate levels of chemical characterization for botanicals as complex mixtures; 3) identify pragmatic, fit-for-purpose NAMs to evaluate botanical safety; 4) evaluate the application of these tools via comparison to the currently available safety information on selected botanicals; 5) and integrate these tools into a framework that can facilitate the evaluation of botanicals. Initially, the BSC is focused on oral exposure from dietary supplements, but this scope could be expanded in future phases of work. This commentary provides an overview of the structure, goals, and strategies of this initiative and insights regarding our first objectives, namely the selection and prioritization of botanicals based on putative toxicological properties.


Assuntos
Produtos Biológicos/normas , Qualidade de Produtos para o Consumidor/normas , Suplementos Nutricionais/normas , Preparações de Plantas/normas , Parcerias Público-Privadas/organização & administração , Suplementos Nutricionais/toxicidade , Preparações de Plantas/toxicidade , Plantas Medicinais/toxicidade , Medição de Risco
5.
J Nat Prod ; 84(3): 846-856, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33710886

RESUMO

Curcuma longa (turmeric) has an extensive history of ethnomedical use for common ailments, and "curcumin"-containing dietary supplements (CDS) are a highly visible portion of today's self-medication market. Owing to raw material cost pressure, CDS products are affected by economically motivated, nefarious adulteration with synthetic curcumin ("syncumin"), possibly leading to unexpected toxicological issues due to "residual" impurities. Using a combination of targeted and untargeted (phyto)chemical analysis, this study investigated the botanical integrity of two commercial "turmeric" CDS with vitamin and other additives that were associated with reported clinical cases of hepatotoxicity. Analyzing multisolvent extracts of the CDS by 100% quantitative 1H NMR (qHNMR), alone and in combination with countercurrent separation (CCS), provided chemical fingerprints that allowed both the targeted identification and quantification of declared components and the untargeted recognition of adulteration. While confirming the presence of curcumin as a major constituent, the universal detection capability of NMR spectroscopy identification of significant residual impurities, including potentially toxic components. While the loss-free nature of CCS captured a wide polarity range of declared and unwanted chemical components, and also increased the dynamic range of the analysis, (q)HNMR determined their mass proportions and chemical constitutions. The results demonstrate that NMR spectroscopy can recognize undeclared constituents even if they represent only a fraction of the mass balance of a dietary supplement product. The chemical information associated with the missing 4.8% and 7.4% (m/m) in the two commercial samples, exhibiting an otherwise adequate curcumin content of 95.2% and 92.6%, respectively, pointed to a product integrity issue and adulteration with undeclared synthetic curcumin. Impurities from synthesis are most plausibly the cause of the observed adverse clinical effects. The study exemplifies how the simultaneously targeted and untargeted analytical principle of the 100% qHNMR method, performed with entry-level high-field instrumentation (400 MHz), can enhance the safety of dietary supplements by identifying adulterated, non-natural "natural" products.


Assuntos
Curcuma/química , Contaminação de Medicamentos , Extratos Vegetais/análise , Distribuição Contracorrente , Curcumina/análise , Suplementos Nutricionais/análise , Espectroscopia de Ressonância Magnética , Extratos Vegetais/normas
6.
Phytother Res ; 35(6): 3013-3031, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33373071

RESUMO

In times of health crisis, including the current COVID-19 pandemic, the potential benefit of botanical drugs and supplements emerges as a focus of attention, although controversial efficacy claims are rightly a concern. Phytotherapy has an established role in everyday self-care and health care, but, since botanical preparations contain many chemical constituents rather than single compounds, challenges arise in demonstrating efficacy and safety. However, there is ample traditional, empirical, and clinical evidence that botanicals can offer some protection and alleviation of disease symptoms as well as promoting general well-being. Newly emerging viral infections, specifically COVID-19, represent a unique challenge in their novelty and absence of established antiviral treatment or immunization. We discuss here the roles and limitations of phytotherapy in helping to prevent and address viral infections, especially regarding their effects on immune response. Botanicals with a documented immunomodulatory, immunostimulatory, and antiinflammatory effects include adaptogens, Boswellia spp., Curcuma longa, Echinacea spp., Glycyrrhiza spp., medicinal fungi, Pelargonium sidoides, salicylate-yielding herbs, and Sambucus spp. We further provide a clinical perspective on applications and safety of these herbs in prevention, onset, progression, and convalescence from respiratory viral infections.


Assuntos
Tratamento Farmacológico da COVID-19 , Preparações de Plantas/farmacologia , Plantas Medicinais/química , Suplementos Nutricionais , Humanos , Imunidade/efeitos dos fármacos , Fitoterapia/métodos , SARS-CoV-2/efeitos dos fármacos
7.
Planta Med ; 86(10): 674-685, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32434255

RESUMO

Maca (Lepidium meyenii, synonym L. peruvianum) was analyzed using a systematic approach employing principal component analysis of flow injection mass spectrometry fingerprints (no chromatographic separation) to guide the selection of samples for metabolite profiling and DNA next generation sequencing. Samples consisted of 39 commercial maca supplements from 11 manufacturers, 31 unprocessed maca tubers grown in Peru and China, and a historic non-tuber maca sample from Peru. Principal component analysis of flow injection mass spectrometry fingerprints initially placed all the maca samples in three classes with similar chemical composition: commercial maca samples, tubers grown in Peru, and tubers grown in China. Metabolite profiling identified 67 compounds in the negative mode and 51 compounds in the positive mode. Compounds identified by metabolite profiling (macamides, glucosinolates, amino acids, fatty acids, polyunsaturated fatty acids, saccharides, imidazoles) were then used to identify ions in the flow injection mass spectrometry fingerprints. The tuber fingerprints were analyzed by factorial multivariate analysis of variance revealing that black, red, and yellow maca from Peru and black and yellow maca from China were compositionally different with respect to color and country. Critical ions were identified that allowed for the differentiation of maca between colors from the same country or between two countries with the same color. Genetically, all samples were confirmed to be L. meyenii based on next generation sequencing at three gene regions (ITS2, psbA, and trnL) and comparison to recorded sequences of vouchered standards.


Assuntos
Lepidium , China , Metabolômica , Peru , Extratos Vegetais
8.
Planta Med ; 82(14): 1225-35, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27392246

RESUMO

In the past decades, the use of traditional medicine has increased globally, leading to a booming herbal medicine and dietary supplement industry. The increased popularity of herbal products has led to a rise in demand for botanical raw materials. Accurate identification of medicinal herbs is a legal requirement in most countries and prerequisite for delivering a quality product that meets consumer expectations. Traditional identification methods include botanical taxonomy, macroscopic and microscopic examination, and chemical methods. Advances in the identification of biological species using DNA-based techniques have led to the development of a DNA marker-based platform for authentication of plant materials. DNA barcoding, in particular, has been proposed as a means to identify herbal ingredients and to detect adulteration. However, general barcoding techniques using universal primers have been shown to provide mixed results with regard to data accuracy. Further technological advances such as mini-barcodes, digital polymerase chain reaction, and next generation sequencing provide additional tools for the authentication of herbs, and may be successful in identifying processed ingredients used in finished herbal products. This review gives an overview on the strengths and limitations of DNA barcoding techniques for botanical ingredient identification. Based on the available information, we do not recommend the use of universal primers for DNA barcoding of processed plant material as a sole means of species identification, but suggest an approach combining DNA-based methods using genus- or species-specific primers, chemical analysis, and microscopic and macroscopic methods for the successful authentication of botanical ingredients used in the herbal dietary supplement industry.


Assuntos
Código de Barras de DNA Taxonômico , Suplementos Nutricionais , Medicina Herbária , Plantas Medicinais/classificação , DNA de Plantas , Suplementos Nutricionais/normas , Medicina Herbária/normas , Plantas Medicinais/genética , Reprodutibilidade dos Testes
9.
Planta Med ; 82(11-12): 1058-69, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27224266

RESUMO

A selective UHPLC-DAD-QToF-MS method was developed to screen grapefruit seeds, and the seeds of other Citrus species for limonoid aglycones, acids, glucosides, and flavonoids. These classes of compounds were identified in positive and negative ion modes over a mass-to-charge range from 100-1500. Accurate mass values, elution times, and fragmentation patterns obtained by QToF-mass spectrometry were used to identify or tentatively characterize the compounds detected in the sample of this study. Limonin was the major limonoid in most of the seeds of Citrus species, followed by nomilin. This analytical method was successfully applied for the analysis of commercial extracts and dietary supplements claiming to contain grapefruit seed extract, or extracts made from the seed and other fruit parts such as the peel or pulp. Many commercial products contained large numbers of flavonoids, indicating the use of peel, pulp, or seed coat. This method also permitted detection of synthetic preservatives such as benzethonium chloride, methylparaben, and triclosan in commercial grapefruit seed extract products. Out of the 17 commercial products analyzed, two contained the synthetic antimicrobial agent benzethonium chloride.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Citrus paradisi/química , Citrus/química , Suplementos Nutricionais , Flavonoides/análise , Limoninas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Sementes/química
10.
Anal Bioanal Chem ; 407(25): 7733-46, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26297458

RESUMO

Ginkgo biloba is one of the most widely sold herbal supplements and medicines in the world. Its popularity stems from having a positive effect on memory and the circulatory system in clinical studies. As ginkgo popularity increased, non-proprietary extracts were introduced claiming to have a similar phytochemical profile as the clinically tested extracts. The standardized commercial extracts of G. biloba leaf used in ginkgo supplements contain not less than 6% sesquiterpene lactones and 24% flavonol glycosides. While sesquiterpene lactones are unique constituents of ginkgo leaf, the flavonol glycosides are found in many other botanical extracts. Being a high value botanical, low quality ginkgo extracts may be subjected to adulteration with flavonoids to meet the requirement of 24% flavonol glycosides. Chemical analysis by ultra high performance liquid chromatography-mass spectrometry revealed that adulteration of ginkgo leaf extracts in many of these products is common, the naturally flavonol glycoside-rich extract being spiked with pure flavonoids or extracts made from another flavonoid-rich material, such as the fruit/flower of Japanese sophora (Styphnolobium japonicum), which also contains the isoflavone genistein. Recently, genistein has been proposed as an analytical marker for the detection of adulteration of ginkgo extracts with S. japonicum. This study confirms that botanically authenticated G. biloba leaf and extracts made therefrom do not contain genistein, and the presence of which even in trace amounts is suggestive of adulteration. In addition to the mass spectrometric approach, a high performance thin layer chromatography method was developed as a fast and economic method for chemical fingerprint analysis of ginkgo samples.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia em Camada Fina/métodos , Suplementos Nutricionais/análise , Contaminação de Medicamentos , Ginkgo biloba/química , Extratos Vegetais/química , Folhas de Planta/química , Flavonoides/análise , Flavonóis/análise , Genisteína/análise , Glicosídeos/análise , Espectrometria de Massas/métodos
11.
J Nat Prod ; 77(3): 521-6, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24479468

RESUMO

Continuing investigation of fractions from a supercritical fluid extract of Chinese licorice (Glycyrrhiza uralensis) roots has led to the isolation of 12 phenolic compounds, of which seven were described previously from this extract. In addition to these seven metabolites, four known components, 1-methoxyerythrabyssin II (4), 6,8-diprenylgenistein, gancaonin G (5), and isoglycyrol (6), and one new isoflavan, licorisoflavan C (7), were characterized from this material for the first time. Treatment of licoricidin (1) with palladium chloride afforded larger amounts of 7 and also yielded two new isoflavans, licorisoflavan D (8), which was subsequently detected in the licorice extract, and licorisoflavan E (9). Compounds 1-9 were evaluated for their antibacterial activities against the cariogenic Streptococcus mutans and the periodontopathogenic Porphyromonas gingivalis. Licoricidin (1), licorisoflavan A (2), and 7-9 showed antibacterial activity against P. gingivalis (MICs of 1.56-12.5 µg/mL). The most potent activity against S. mutans was obtained with 7 (MIC of 6.25 µg/mL), followed by 1 and 9 (MIC of 12.5 µg/mL). This study provides further evidence for the therapeutic potential of licorice extracts for the treatment and prevention of oral infections.


Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Glycyrrhiza uralensis/química , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Piranos/isolamento & purificação , Piranos/farmacologia , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/química , Benzopiranos/química , Genisteína/análogos & derivados , Genisteína/química , Alemanha , Glycyrrhiza/metabolismo , Isoflavonas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Paládio/farmacologia , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Raízes de Plantas/química , Pterocarpanos/química , Pterocarpanos/isolamento & purificação , Piranos/química
12.
Food Chem Toxicol ; 186: 114537, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417538

RESUMO

Increases in botanical use, encompassing herbal medicines and dietary supplements, have underlined a critical need for an advancement in safety assessment methodologies. However, botanicals present unique challenges for safety assessment due to their complex and variable composition arising from diverse growing conditions, processing methods, and plant varieties. Historically, botanicals have been largely evaluated based on their history of use information, based primarily on traditional use or dietary history. However, this presumption lacks comprehensive toxicological evaluation, demanding innovative and consistent assessment strategies. To address these challenges, the Botanical Safety Consortium (BSC) was formed as an international, cross-sector forum of experts to identify fit-for purpose assays that can be used to evaluate botanical safety. This global effort aims to assess botanical safety assessment methodologies, merging traditional knowledge with modern in vitro and in silico assays. The ultimate goal is to champion the development of toxicity tools for botanicals. This manuscript highlights: 1) BSC's strategy for botanical selection, sourcing, and preparation of extracts to be used in in vitro assays, and 2) the approach utilized to characterize botanical extracts, using green tea and Asian ginseng as examples, to build confidence for use in biological assays.


Assuntos
Plantas Medicinais , Suplementos Nutricionais , Chá
13.
Curr Opin Toxicol ; 322022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36311298

RESUMO

Botanicals can cause nephrotoxicity via numerous mechanisms, including disrupting renal blood flow, damaging compartments along the nephron, and obstructing urinary flow. While uncommon, there are various reports of botanical-induced nephrotoxicity in the literature, such as from aristolochia (Aristolochia spp.) and rhubarb (Rheum spp.). However, at present, it is a challenge to assess the toxic potential of botanicals because their chemical composition is variable due to factors such as growing conditions and extraction techniques. Therefore, selecting a single representative sample for an in vivo study is difficult. Given the increasing use of botanicals as dietary supplements and herbal medicine, new approach methodologies (NAMs) are needed to evaluate the potential for renal toxicity to ensure public safety. Such approaches include in vitro models that use layers of physiological complexity to emulate the in vivo microenvironment, enhance the functional viability and differentiation of cell cultures, and improve sensitivity to nephrotoxic insults. Furthermore, computational tools such as physiologically based pharmacokinetic (PBPK) modeling can add confidence to these tools by simulating absorption, distribution, metabolism, and excretion. The development and implementation of NAMs for renal toxicity testing will allow specific mechanistic data to be generated, leading to a better understanding of the nephrotoxic potential of botanicals.

14.
Front Pharmacol ; 13: 981978, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249773

RESUMO

Dietary supplement current good manufacturing practice (cGMP) requires establishment of quality parameters for each component used in the manufacture of a dietary supplement to ensure that specifications for the identity, purity, strength, composition, and limits on contaminants are met. Compliance with botanical extract ingredient specifications is assured by using scientifically valid methods of analysis, the results of which are reported on certificates of analysis (CoAs). However, CoAs routinely include additional data that are not amenable to verification through methods of analysis. Such descriptive information may include Plant to Extract ratios, which are ratios of the quantity of botanical article used in the manufacture of the extract to the quantity of extract obtained. Plant to Extract ratios can be misleading when their meaning is not clearly understood. Plant to Extract ratios do not completely describe botanical extracts because other important factors influence the make-up of final extracts, such as the quality of the raw starting material (as can defined by pharmacopeial standards), extraction solvent(s) used, duration and temperature of extraction, and percentage and type of excipients present. Other important qualitative descriptions may include constituent "fingerprinting." Despite these issues, Plant to Extract ratios are often used as a measure of extract strength for dosage calculations. This article defines and clarifies the meaning of Plant to Extract ratios and their proper use in describing and labeling botanical extract ingredients and finished products containing them.

15.
J Nat Prod ; 74(12): 2514-9, 2011 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-22074222

RESUMO

Phytochemical investigation of a supercritical fluid extract of Glycyrrhiza uralensis has led to the isolation of 20 known isoflavonoids and coumarins, and glycycarpan (7), a new pterocarpan. The presence of two isoflavan-quinones, licoriquinone A (8) and licoriquinone B (9), in a fraction subjected to gel filtration on Sephadex LH-20 is due to suspected metal-catalyzed oxidative degradation of licoricidin (1) and licorisoflavan A (2). The major compounds in the extract, as well as 8, were evaluated for their ability to inhibit the growth of several major oral pathogens. Compounds 1 and 2 showed the most potent antibacterial activities, causing a marked growth inhibition of the cariogenic species Streptococcus mutans and Streptococcus sobrinus at 10 µg/mL and the periodontopathogenic species Porphyromonas gingivalis (at 5 µg/mL) and Prevotella intermedia (at 5 µg/mL for 1 and 2.5 µg/mL for 2). Only 1 moderately inhibited growth of Fusobacterium nucleatum at the highest concentration tested (10 µg/mL).


Assuntos
Antibacterianos , Cumarínicos , Isoflavonas , Pterocarpanos/isolamento & purificação , Quinonas , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Benzopiranos/química , Benzopiranos/metabolismo , Benzopiranos/farmacologia , Cumarínicos/química , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Relação Dose-Resposta a Droga , Fusobacterium nucleatum/efeitos dos fármacos , Alemanha , Glycyrrhiza uralensis , Humanos , Isoflavonas/química , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , Testes de Sensibilidade Microbiana , Porphyromonas gingivalis/efeitos dos fármacos , Pterocarpanos/química , Pterocarpanos/farmacologia , Quinonas/química , Quinonas/isolamento & purificação , Quinonas/metabolismo , Quinonas/farmacologia , Streptococcus mutans/efeitos dos fármacos , Streptococcus sobrinus/efeitos dos fármacos
16.
J Periodontol ; 79(9): 1752-61, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18771378

RESUMO

BACKGROUND: Periodontal diseases are a group of inflammatory disorders initiated by specific Gram-negative periodontopathogenic bacteria that lead to the destruction of tooth-supporting tissues. In this study, we tested whether a carbon dioxide-supercritical extract of Glycyrrhiza uralensis (licorice) can reduce the periodontopathogen-induced inflammatory response. METHODS: Monocyte-derived macrophages were treated with various concentrations of the licorice extract prior to being stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) and Porphyromonas gingivalis lipopolysaccharide (LPS). The capacity of the licorice extract to mediate the inflammatory response was also tested in an ex vivo whole blood model stimulated with P. gingivalis LPS. The secretion of interleukin (IL)-1beta, -6, and -8 and tumor necrosis factor-alpha (TNF-alpha) in both models was assessed by enzyme-linked immunosorbent assays. Changes in the phosphorylation state of macrophage intracellular kinases induced by A. actinomycetemcomitans LPS and the licorice extract in the macrophage model were characterized by immunoblotting. RESULTS: The licorice extract exhibited potent anti-inflammatory properties, inhibiting the periodontopathogen LPS-induced IL-1beta, -6, and -8 and TNF-alpha responses of macrophages. The licorice extract inhibited the phosphorylation of important macrophage intracellular signaling proteins, including nuclear factor-kappa B p65 nuclear transcription factor and Jun proto-oncogene-encoded activator protein (AP) 1 transcription factor, which are involved in inflammatory signaling pathways. The licorice extract was also a potent inhibitor of the proinflammatory cytokine response in the ex vivo human whole blood model. CONCLUSION: This CO(2)-supercritical licorice extract is a potential candidate for the development of a new therapy to prevent and/or treat periodontitis-associated tissue destruction.


Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/efeitos dos fármacos , Glycyrrhiza , Mediadores da Inflamação/análise , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Aggregatibacter actinomycetemcomitans , Citocinas/sangue , Humanos , Immunoblotting , Interleucina-1beta/sangue , Interleucina-1beta/efeitos dos fármacos , Interleucina-6/análise , Interleucina-6/sangue , Interleucina-8/sangue , Interleucina-8/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Lipopolissacarídeos/antagonistas & inibidores , Macrófagos/enzimologia , Proteína Quinase 7 Ativada por Mitógeno/efeitos dos fármacos , Doenças Periodontais/sangue , Doenças Periodontais/microbiologia , Fosforilação , Porphyromonas gingivalis , Proto-Oncogene Mas , Fator de Transcrição AP-1/efeitos dos fármacos , Fator de Transcrição RelA/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/efeitos dos fármacos
17.
J Agric Food Chem ; 53(8): 3076-80, 2005 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-15826062

RESUMO

The aqueous extract of American skullcap (Scutellaria lateriflora L. (S. lateriflora), Lamiaceae) has been traditionally used by North American Indians as a nerve tonic and for its sedative and diuretic properties. Recent reports stated that flavonoids and possibly amino acids are responsible for the anxiolytic activity. As a part of our search for environmentally friendly solvents to extract the active components from medicinal plants, we used S. lateriflora in a comparison of accelerated solvent extraction (ASE) using water, and supercritical fluid extraction (SFE) using CO2 and 10% EtOH as modifier, at different temperatures. Flavonoids and amino acids were quantified by HPLC-UV and HPLC-MS, respectively. The flavonoid content was compared with conventional extraction methods (hot water extraction and 70% ethanol). The use of ASE at 85 degrees C with water as solvent gave the best results for flavonoid glycosides and amino acids, whereas SFE gave higher yields of flavonoid aglycones. However, the results obtained for total flavonoids were not significatively superior to hot water extraction or 70% aqueous EtOH extract.


Assuntos
Cromatografia com Fluido Supercrítico , Etanol , Extratos Vegetais/química , Scutellaria/química , Água , Aminoácidos/análise , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Solventes
18.
Phytochemistry ; 65(21): 2849-59, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15501252

RESUMO

Curcumin is a natural product widely used as a spice in food. It has been shown to inhibit cyclooxygenase (COX)-1 and -2 and to suppress lipopolysaccharide-induced COX-2 and iNOS gene expression. In the present study, curcumin and 22 of its derivatives were evaluated for their chemopreventive potential. Based on COX-2 inhibition, curcumin (IC50=15.9 microM), 1,7-bis(3-fluoro-4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (19) (IC50=23.7 microM) and 2,6-bis(3-fluoro-4-hydroxybenzylidene)cyclohexanone (23) (IC50=5.5 microM) were found to be most potent. Tricyclic derivatives 2,6-bis(4-hydroxy-3-methoxybenzylidene)cyclohexanone (10), 2,6-bis(4-hydroxy-3,5-dimethoxybenzylidene)cyclohexanone (13) and 2,5-bis(4-hydroxy-3,5-dimethoxybenzylidene)cyclopentanone (21) inhibited LPS-induced COX-2 and iNOS gene expression in murine macrophages with potency equal to curcumin. RT-PCR experiments demonstrated suppression of COX-2 and iNOS gene expression occurred at the transcriptional level. The most active compounds in the macrophage assays, 13 and 23, were also the most cytotoxic, however. Topical application of curcumin, 10, 13, 21, and 6, a methoxy derivative of curcumin, showed strong inhibition of 12-O-tetradecanoyl-13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity in mouse skin. These data suggest that structural elements responsible for COX-1 and COX-2 inhibition do not correlate well with those responsible for inhibiting COX-2 and iNOS gene expression, but elements capable of inhibiting COX-2 and iNOS gene expression also contribute to inhibition of TPA-induced ODC activity. The most potent compounds in these assays, 10, 13 and 21, as well as curcumin, were further evaluated for inhibition of 7,12-dimethylbenz(a)anthracene (DMBA)-induced preneoplastic lesion formation in a mouse mammary organ culture model, and dose-dependent responses were observed. Most potent effects were at concentrations between 1 and 5 microM for 10, 13 and 21, and at 10 microM for curcumin. These data demonstrate the substitution pattern on the aromatic moiety is especially crucial for activity.


Assuntos
Anticarcinógenos/farmacologia , Curcumina/análogos & derivados , Curcumina/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Feminino , Isoenzimas/antagonistas & inibidores , Neoplasias Mamárias Experimentais/prevenção & controle , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II , Inibidores da Ornitina Descarboxilase , Monoéster Fosfórico Hidrolases/metabolismo , Prostaglandina-Endoperóxido Sintases
19.
J Agric Food Chem ; 50(14): 3967-70, 2002 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-12083867

RESUMO

Recent work has shown that enzymatic degradation and oxidation of cichoric acid and other caffeic derivatives occurs in Echinacea preparations. However, very little is known as to the means of stabilizing these phytopreparations. To stabilize the glycerin extract of Echinacea purpurea, we have evaluated the effects of 3 natural antioxidants (citric acid, malic acid, and hibiscus extract) on the stability of the major caffeic acid derivatives (caftaric acid, caffeic acid, cichoric acid, and 2-O-feruloyl-tartaric acid). Chlorogenic acid, which normally occurs in an ethanol extract of E. purpurea, was not present in the glycerin extract. The caffeic acid derivatives, with the exception of 2-O-feruloyl-tartaric acid, were subject to degradation in the control sample. 2-O-Feruloyl-tartaric acid was stable during the whole testing period. All antioxidant treatments greatly improved the stability of caffeic acid derivatives. Stability was dependent upon the concentration of antioxidant added.


Assuntos
Antioxidantes/farmacologia , Ácidos Cafeicos/química , Ácido Clorogênico/análogos & derivados , Echinacea/química , Glicerol , Extratos Vegetais/química , Succinatos , Ácido Clorogênico/química , Cromatografia Líquida de Alta Pressão , Ácido Cítrico/farmacologia , Estabilidade de Medicamentos , Malatos/farmacologia , Malvaceae/química , Tartaratos/química
20.
J Agric Food Chem ; 52(6): 1546-50, 2004 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-15030209

RESUMO

Despite the wide availability of liquid herbal extracts using mixtures of alcohol, glycerin, and water, or glycerin and water as solvents, no data on the chemical composition of such extracts is readily available. In this study, the amount and the stability of the major saponins in Panax quinquefolius root extracts, made either with 50% (v/v) aqueous ethanol, a mixture (v/v/v) of 20% ethanol, 40% glycerin, and 40% water, or with 65% (v/v) aqueous glycerin, were evaluated by HPLC-UV analysis. The amount of total saponins was highest in the 50% aqueous ethanol extract (61.7 +/- 0.1 mg/g dry root), although similar to the ethanol-glycerin-water extract (59.4 +/- 0.5 mg/g dry root). Saponins were significantly lower in the 65% aqueous glycerin extract (51.5 +/- 0.2 mg/g dry root). Interestingly, the amounts of individual saponins were quite variable depending on the solvent. This is in part due to enzymatic cleavage of ginsenosides in the glycerin containing extracts during the maceration process. Storage of the extracts at 25 degrees C over the period of a year led to a 13-15% loss of saponins with all three types of extractions.


Assuntos
Cromatografia Líquida de Alta Pressão , Panax/química , Raízes de Plantas/química , Saponinas/isolamento & purificação , Etanol , Glicerol , Extratos Vegetais/química , Solventes , Água
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