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BACKGROUND: Pterospermum rubiginosum has been traditionally used by the tribal inhabitants of Southern India for treating bone fractures and as a local anti-inflammatory agent; however, experimental evidence to support this traditional usage is lacking. The present study aimed to investigate the phytochemical characterization, in silico and in vitro anti-inflammatory evaluation, followed by in vivo toxicological screening of P. rubiginosum methanolic bark extract (PRME). RESULTS: The LCMS evaluation revealed the presence of 80 significant peaks; nearly 50 molecules were identified using the LCMS database. In silico analysis showed notable interactions with inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6). In vitro gene expression study supported the docking results with significant down-regulation of iNOS, IL-6, and IL-10. PRME was administered orally to the SD rats and was found to be non-toxic up to 1000 mg/kg body weight for 14 days. The antioxidant enzymes catalase and sodium dismutase exhibited an increased value in PRME-administered groups, possibly due to the diverse phytochemical combinations in bark extract. CONCLUSIONS: PRME administration significantly downregulated the gene expression of inflammatory markers, such as iNOS, IL-6, and IL-10. The molecular docking analysis of iNOS and IL-6 supports the in vitro study. In vivo toxicological study of PRME in SD rats was found to be non-toxic up to a concentration of 1000 mg/kg body weight for 14 days.
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Gum arabic/acacia (GA), derived from Acacia trees, is a versatile natural product offering a broad spectrum of applications. Its rich content of soluble dietary fibers, coupled with a low caloric profile, renders GA a valuable dietary component associated with numerous health benefits. Furthermore, its fermentation by gut microbiota yields short-chain fatty acids, renowned for their positive impact on health. Immunomodulation, a crucially regulated mechanism in the body, serves to fend off pathogenic infections by releasing pro-inflammatory cytokines. However, prolonged synthesis of these cytokines can lead to chronic inflammation, tissue damage, and potentially contribute to the development of autoimmune diseases and cancer. Hence, there is an urgent need to identify plant-based biomolecules that can effectively reduce inflammation and inhibit inflammation-induced complications or disorders. In this context, edible biomolecules like GA are gaining prominence for their noteworthy immunomodulatory properties. Therefore, in the present review we have explored the role of GA in immunomodulation, inflammation, and inflammation-associated metabolic diseases, and cancer.
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Acacia , Neoplasias , Humanos , Goma Arábica/farmacologia , Inflamação , Fibras na Dieta , CitocinasRESUMO
Idelalisib is a selective and second-generation PI3K-δ inhibitor, approved for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia. In this paper, we present a fully validated dried blood spot (DBS) method for the quantitation of idelalisib from mice blood using an LC-MS/MS, which was operated under multiple reaction monitoring mode. To the punched DBS discs, acidified methanol enriched with internal standard (IS; larotrectinib) was added and extracted using tert-butyl methyl ether as an extraction solvent with sonication. Chromatographic separation of idelalisib and the IS was achieved on an Atlantis dC18 column using a mixture of 10 mM ammonium formate:acetonitrile (25:75, v/v). The flow-rate and injection volume were 0.80 mL/min and 2.0 µL, respectively. Idelalisib and the IS were eluted at ~0.98 and 0.93 min, respectively and the total run time was 2.00 min. Idelalisib and the IS were analyzed using positive ion scan mode and parent-daughter mass to charge ion (m/z) transition of 416.1â176.1 and 429.1â342.1, respectively was used for the quantitation. The calibration range was 1.01-4 797 ng/mL. No matrix effect and carry over were observed. Haematocrit did not influence DBS idelalisib concentrations. All the validation parameters met the acceptance criteria. The applicability of the validated method was shown in a mice pharmacokinetic study.
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Teste em Amostras de Sangue Seco/métodos , Monitoramento de Medicamentos/métodos , Purinas/análise , Quinazolinonas/análise , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/análise , Antineoplásicos/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodos , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Avaliação Pré-Clínica de Medicamentos , Meia-Vida , Masculino , Camundongos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/análise , Inibidores de Proteínas Quinases/farmacocinética , Purinas/administração & dosagem , Purinas/farmacocinética , Quinazolinonas/administração & dosagem , Quinazolinonas/farmacocinética , Espectrometria de Massas em Tandem/métodosRESUMO
India's medical heritage across its two streams of experiential knowledge viz. the classical (codified) and folk (oral) reveals an incredible range and depth of knowledge of medicinal plants. In the classical stream of Ayurveda, across the period from 1500 BCE to 1900 CE, there is information of more than 12,000 distinct Sanskrit plant names with overlaps across texts. This information is captured in more than 200 texts viz. 6 samhitas, 57 nighantus and 140 vyakhyas. The information about plants has three major dimensions in codified literature viz. morphological description (rupa gnana), pharmacology (dravya guna shastra) and pharmacy (bhaishajya kalpana). The morphological information is however sketchy and wholly inadequate for establishing botanical identity. Thus despite the huge corpus of plant names backed by sophisticated understanding of pharmacology and pharmacy there is the fact of controversial identities of medicinal plants. Why is this the case? The author believes that the gap in morphological detailing is due to the 'experiential' pedagogy of India's health tradition. While knowledge transmission of plants included theoretical propositions and sophisticated logic related to pharmacology, it also assumed an oral, practical and experiential system of learning about the identity of plants through field work. The purpose of this research is to understand the range and depth at which we have understood the problem of controversial identities of medicinal plants, to analyze work done in the field and to propose a Trans disciplinary approach to solve the problem of controversial identities of medicinal plants in Ayurveda.
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BACKGROUND: Citrus comprises the largest fruit sector worldwide, and its fruit peels are the dominant 'residue' of the industry. Though not profitable, Citrus peels are industrially used for making some byproducts (cattle feed, molasses, ethanol, fiber) and for the extraction of bioactives (flavonoids, essential oils, d-limonene). Still huge amounts of peels are wasted by Citrus industries, juice and other vending sectors. PURPOSE: The biological potentials of these unutilized or 'wasted' Citrus peels are least exploited. Here we tested the anticancer potentials of Citrus medica (2 morphotypes), C. sinensis, C. maxima, C. limon and C. reticulata peels by in vitro assays and in vivo cancer models. METHODS: Chemical profiles of Citrus peel oils and peel extracts were analyzed by gas chromatographic techniques (GC-FID, GC-MS) and HPTLC-densitometry, respectively. Anticancer potentials of Citrus peels (Citrus medica 2 morphotypes, C. sinensis, C. maxima, C. limon and C. reticulata) were evaluated by various in vitro assays (MTT assay, morphological observations, fast halo assay, flow cytometric analysis) and in vivo cancer models. RESULTS: C. reticulata peels (extracts, essential oils) showed significant activity against DLA cell line in MTT assay. We found C. reticulata peel water extract inducing cell cycle arrest of DLA in G0/G1 phase followed by nuclear condensation, membrane blebbing, formation of apoptotic bodies and DNA damage leading to apoptosis. In in vivo experiments, C. reticulata peel extract pre-treated mice were significantly (50%) protected from DLA compared to post-treated mice (33%), without any conspicuous toxic symptoms. Citrus peels have volatiles (essential oils, limonoids) and non-volatiles (mainly polymethoxy flavones) as their bioactive/anticancer constituents. CONCLUSION: Our results encourage the use of Citrus peels, which is wasted in huge amounts, as cancer preventive food additives and as anticancer agents.
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Antineoplásicos/farmacologia , Citrus/química , Frutas/química , Neoplasias Experimentais/tratamento farmacológico , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Animais , Linhagem Celular Tumoral , Flavonoides/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Limoneno/farmacologia , Masculino , CamundongosRESUMO
BACKGROUND: The Valaiyar (Moopanar) communities of Tamil Nadu are traditionally known for catching rats and snakes from the agricultural fields. Prior to independence, some of these families have faced socio-economic changes and chosen to become herbalists in Madurai city. They are mainly engaged in collecting and dispensing fresh and dried plant drugs in its 'natural form' at Tilagar tidal market of Madurai city. Their business is unique, because customers receive 'prescriptions' and 'plant drugs', unlike the conventional dispensaries. Their world view is: 'to cure the ailing in natural way'. OBJECTIVES: To document plant drugs collected and dispensed by some of the families belonging to Valaiyar (Moopanar) community in the Tilagar tidal market. MATERIALS AND METHODS: Ethnobotanical tools were employed to document various aspects of the practices including resource and knowledge base, medicinal uses, dosage, collection of herbarium and raw drug specimens. Integrative approach was adapted to document the trade dynamics. RESULTS: During the study, 133 medicinal plant species belonging to 50 families were documented. 71% of species were sourced from wild and non-forest areas. 272 simple and compound remedies were recorded. CONCLUSION: Local markets/shanties like these are 'Traditional Medicine (TM) health care services at door step'. They cater to local health care needs along with conventional system in a synergistic manner and provide adaptable, local solutions using local resources.
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BACKGROUND: Solanum nigrum, herbal plant that commonly grows in temperate climate zone, has been used as a traditional folk medicine whose ripen fruits were proven to exhibit anti-tumor properties. In traditional Chinese medicine, it has been used for centuries to cure inflammation, edema, mastitis and hepatic cancer and in the Ayurvedic system of traditional medicine in India, S. nigrum is applied against enteric diseases, ulcer, diarrhea and skin diseases. A methanolic glycosidic extract fraction of unripe fruit of S. nigrum (SNME) was investigated for its anticancer property and possible mechanism to surmount adriamycin resistance in NCI/ADR-RES cells. METHODS: The NCI/ADR-RES cells were treated with 7.8125, 15.625, 31.25, 62.5, 125 and 250 µg/ml of methanolic extract of S. nigrum (SNME) for 12, 24 and 48 h, to check the cell viability and proliferation. The cells were also exposed to adriamycin alone or in combination with SNME and the effects on cell growth were determined by MTT. Cell cycle analysis, Ethidium bromide and Acridine orange staining, Annexin-binding efficiency, nuclear condensation and DNA fragmentation of the apoptotic NCI/ADR-RES cells were also determined. To elucidate the relationship between SNME and multi drug resistance, we analyzed the expression levels of Mdr-1, JAK1, STAT3, and pSTAT3 in NCI/ADR-RES cells after treatment with SNME. RESULTS: Results from the cytotoxicity assay showed a direct correlation between the concentration of methanolic glycosidic extract fraction of S. nigrum (SNME) and the surviving cell population. Combination with Adriamycin, SNME exhibits a synergistic action on NCI/ADR-RES cells, giving the first line of evidence to overcoming Adriamycin resistance. The SNME mediated cell growth suppression was proven to be apoptotic, based on results obtained from DNA fragmentation, annexin V apoptosis assaay and PARP cleavage analysis. Looking into the molecular insight SNME surpasses the chemoresistance of NCI/ADR-RES cells by inhibiting the JAK-STAT3 signaling pathway through the down regulation of JAK1, STAT3, pSTAT3, and Mdr1 expression. CONCLUSIONS: Collectively our findings suggest that unripe fruit of Solanum nigrum could possibly be used as a chemosensitizing agent against Adriamycin resistant cancers.
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Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Neoplasias/metabolismo , Extratos Vegetais/farmacologia , Solanum nigrum , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Regulação para Baixo , Doxorrubicina/uso terapêutico , Sinergismo Farmacológico , Frutas , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Humanos , Janus Quinase 1/metabolismo , Medicina Tradicional , Neoplasias/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Transdução de SinaisRESUMO
Introduction Increased physical activity and functional ability are the goals of total knee replacement surgery. Therefore, adequate rehabilitation is required for the recovery of patients after discharge from hospital following total knee arthroplasty (TKA). This systematic literature review aimed to evaluate the effectiveness of home telerehabilitation in patients who underwent TKA. Methods Studies published in the English language between 2000 and 2014 were retrieved from Embase, PubMed, and Cochrane databases using relevant search strategies. Two researchers independently reviewed the studies as per the Cochrane methodology for systematic literature review. We considered telerehabilitation sessions as those that were conducted by experienced physiotherapists, using videoconferencing to patients' homes via an internet connection. The outcomes assessed included: knee movement (knee extension and flexion); quadriceps muscle strength; functional assessment (the timed up-and-go test); and assessment of pain, stiffness, and functional capacity using the Western Ontario and McMaster Universities Osteoarthritis Index and visual analogue scale for pain. Results In total, 160 potentially relevant studies were screened. Following the screening of studies as abstracts and full-text publications, six primary publications (four randomized controlled trials, one non-randomized controlled trial, and one single-arm trial) were included in the review. Patients experienced high levels of satisfaction with the use of telerehabilitation alone. There was no significant difference in change in active knee extension and flexion in the home telerehabilitation group as compared to the control group (mean difference (MD) -0.52, 95% CI -1.39 to 0.35, p = 0.24 and MD 1.14, 95% CI -0.61 to 2.89, p = 0.20, respectively). The patients in the home telerehabilitation group showed improvement in physical activity and functional status similar to patients in the conventional therapy group. Discussion The evidence from this systematic literature review demonstrated that telerehabilitation is a practical alternative to conventional face-to-face rehabilitation therapy in patients who underwent TKA.
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Artroplastia do Joelho/reabilitação , Telerreabilitação , Humanos , Telerreabilitação/métodos , Resultado do TratamentoRESUMO
ETHANOPHARMACOLOGICAL RELEVANCE: Andrographolide is a herbal extract traditionally used in South Asian countries for treating inflammatory diseases. AIM OF THE STUDY: To evaluate the efficacy of andrographolide in management of periodontal disease which is a highly prevalent oral disease. MATERIALS AND METHODS: Periodontal ligament fibroblasts (PDLF) were cultured from healthy and diseased periodontium using explant culture methods. The safe dose of AG was determined using MTT assay. LPS (lipopolysaccharide) of the most important periodontopathogen, P gingivalis was used to activate NF-κB and STAT3 in PDLF. The efficacy of AG in inhibiting NF-κB and STAT3 was analyzed using immunofluorescence. Down regulation of expression of target genes of these transcription factors related to inflammation and bone resorption were analyzed using real time PCR. RESULTS: AG up to the concentration of 25µM was found to be safe as determined by MTT assay. Statistically significant activation of NF-κB and STAT3 in cultured PDLF was observed in diseased group compared to healthy controls before and after LPS challenge. 5µM AG pretreatment significantly inhibited activation of NF-κB and STAT3 and down regulated expression of inflammatory and bone resorptive genes in cultured PDLF. CONCLUSIONS: The findings of the present study propose the adjunctive use of a novel herbal drug andrographolide as a promising host modulation agent for periodontal therapy by inhibiting NF-κB and STAT3 activation and inhibition of inflammation and bone resorption related genes.
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Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Fibroblastos/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Fator de Transcrição STAT3/antagonistas & inibidores , Adulto , Células Cultivadas , Ciclo-Oxigenase 2/genética , Feminino , Fibroblastos/metabolismo , Humanos , Interleucina-1beta/genética , Lipopolissacarídeos , Masculino , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Doenças Periodontais/tratamento farmacológico , Doenças Periodontais/metabolismo , Ligamento Periodontal/citologia , Ligante RANK/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
OBJECTIVE: In end-stage knee osteoarthritis the treatment of choice is total knee arthroplasty (TKA). An alternative treatment is knee joint distraction (KJD), suggested to postpone TKA. Several studies reported significant and prolonged clinical improvement of KJD. To make an appropriate decision regarding the position of this treatment, a cost-effectiveness and cost-utility analysis from healthcare perspective for different age and gender categories was performed. METHODS: A treatment strategy starting with TKA and a strategy starting with KJD for patients of different age and gender was simulated. To extrapolate outcomes to long-term health and economic outcomes a Markov (Health state) model was used. The number of surgeries, QALYs, and treatment costs per strategy were calculated. Costs-effectiveness is expressed using the cost-effectiveness plane and cost-effectiveness acceptability curves. RESULTS: Starting with KJD the number of knee replacing procedures could be reduced, most clearly in the younger age categories; especially revision surgery. This resulted in the KJD strategy being dominant (more effective with cost-savings) in about 80% of simulations (with only inferiority in about 1%) in these age categories when compared to TKA. At a willingness to pay of 20.000 Euro per QALY gained, the probability of starting with KJD to be cost-effective compared to starting with a TKA was already found to be over 75% for all age categories and over 90-95% for the younger age categories. CONCLUSION: A treatment strategy starting with knee joint distraction for knee osteoarthritis has a large potential for being a cost-effective intervention, especially for the relatively young patient.
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Artroplastia do Joelho/economia , Análise Custo-Benefício , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/economia , Osteoartrite do Joelho/cirurgia , Osteogênese por Distração/economia , Idoso , Simulação por Computador , Feminino , Humanos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Anos de Vida Ajustados por Qualidade de Vida , Resultado do TratamentoRESUMO
Dictyota menstrualis (Hoyt) Schnetter, Hörning & Weber-Peukert (Dictyotales, Phaeophyceae) was studied for the production of oil-based bioproducts and co-products. Experiments were performed to evaluate the effect of carbon dioxide (CO2) concentration, under nitrogen (NO3 (-)) limiting and saturation conditions, on growth rate (GR), photosynthesis, as well as nitrate reductase (NR), carbonic anhydrase (CA), and Rubisco activities. In addition, the biochemical composition of D. menstrualis under these conditions was estimated. GR, protein content, and N content in D. menstrualis were higher in treatments containing NO3 (-), irrespective of CO2 addition. However, when CO2 was added to medium saturated with NO3 (-), values of maximum photosynthesis, Rubisco, and NR activity, as well as total soluble carbohydrates and lipids, were increased. CA activity did not vary under the different treatments. The fatty acid profile of D. menstrualis was characterized by a high content of polyunsaturated fatty acids, especially the omega-3 fatty acids, making it a possible candidate for nutraceutical use. In addition, this species presented high GR, photosynthetic rate, and fatty acid content, highlighting its economic importance and the possibility of different biotechnological applications.
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Dióxido de Carbono/farmacologia , Ácidos Graxos Ômega-3/biossíntese , Nitratos/farmacologia , Phaeophyceae/metabolismo , Fotossíntese/efeitos dos fármacos , Proteínas de Algas/genética , Proteínas de Algas/metabolismo , Reatores Biológicos , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Anidrases Carbônicas/genética , Anidrases Carbônicas/metabolismo , Suplementos Nutricionais/análise , Expressão Gênica , Nitratos/metabolismo , Nitrogênio/metabolismo , Phaeophyceae/genética , Fotoperíodo , Fotossíntese/genética , Ribulose-Bifosfato Carboxilase/genética , Ribulose-Bifosfato Carboxilase/metabolismoRESUMO
Moringa oleifera L. is a medicinal plant with potential antioxidant property. This study was aimed at investigating the chemoprotective effect of Moringa oleifera leaf extract (MOE) on cyclophosphamide (CP)-induced testicular toxicity. Two-week-old male Swiss albino mice were intraperitoneally injected with phosphate-buffered saline, 50 mg kg(-1) of CP and 25 mg kg(-1) of MOE. In combination treatment, mice were injected with 25 mg kg(-1) of MOE 24 h prior to CP injection, 24 h prior and post-CP injection and 24 h post-CP injection for 5 consecutive days (10 mg kg(-1) ). Six weeks later, mice were sacrificed to assess epididymal sperm parameters. MOE alone did not have any significant effect on sperm parameters. However, acute injection of CP resulted in significant decline in motility (P < 0.001), increase in head abnormality (P < 0.01) and DNA damage (P < 0.05). Combining MOE with CP increased the sperm density, motility and reduced head defect and DNA damage, irrespective of the schedule and dosage of MOE. Administration of MOE prior to CP significantly elevated the level of superoxide dismutase and catalase with concomitant decrease in lipid peroxidation in the testicular tissue. In conclusion, MOE may have potential benefit in reducing the loss of male gonadal function following chemotherapy.
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Antineoplásicos Alquilantes/toxicidade , Antioxidantes/farmacologia , Ciclofosfamida/toxicidade , Dano ao DNA/efeitos dos fármacos , Moringa oleifera , Extratos Vegetais/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Catalase/efeitos dos fármacos , Catalase/metabolismo , Epididimo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Folhas de Planta , Puberdade , Espermatozoides/citologia , Espermatozoides/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties.
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Alquilantes/toxicidade , Ciclofosfamida/antagonistas & inibidores , Ciclofosfamida/toxicidade , Óleos de Plantas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Nitrogênio da Ureia Sanguínea , Óleo de Coco , Creatinina/metabolismo , Suplementos Nutricionais , Edema/patologia , Edema/prevenção & controle , Formaldeído , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Fígado/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Abstract Alzheimer's disease affects nearly 36.5 million people worldwide, and acetylcholinesterase inhibition is currently considered the main therapeutic strategy against it. Seaweed biodiversity in Brazil represents one of the most important sources of biologically active compounds for applications in phytotherapy. Accordingly, this study aimed to carry out a quantitative and qualitative assessment of Hypnea musciformis (Wulfen) J.V. Lamouroux, Ochtodes secundiramea (Montagne) M.A. Howe, and Pterocladiella capillacea (S.G. Gmelin) Santelices & Hommersand (Rhodophyta) in order to determine the AChE effects from their extracts. As a matter of fact, the O. secundiramea extract showed 48% acetylcholinesterase inhibition at 400 μg/ml. The chemical composition of the bioactive fraction was determined by gas chromatography–mass spectrometry (GC–MS); this fraction is solely composed of halogenated monoterpenes, therefore allowing assignment of acetylcholinesterase inhibition activity to them.
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BACKGROUND: DNA methylation and its perturbations are an established attribute to a wide spectrum of phenotypic variations and disease conditions. Indian traditional system practices personalized medicine through indigenous concept of distinctly descriptive physiological, psychological and anatomical features known as prakriti. Here we attempted to establish DNA methylation differences in these three prakriti phenotypes. METHODS: Following structured and objective measurement of 3416 subjects, whole blood DNA of 147 healthy male individuals belonging to defined prakriti (Vata, Pitta and Kapha) between the age group of 20-30years were subjected to methylated DNA immunoprecipitation (MeDIP) and microarray analysis. After data analysis, prakriti specific signatures were validated through bisulfite DNA sequencing. RESULTS: Differentially methylated regions in CpG islands and shores were significantly enriched in promoters/UTRs and gene body regions. Phenotypes characterized by higher metabolism (Pitta prakriti) in individuals showed distinct promoter (34) and gene body methylation (204), followed by Vata prakriti which correlates to motion showed DNA methylation in 52 promoters and 139 CpG islands and finally individuals with structural attributes (Kapha prakriti) with 23 and 19 promoters and CpG islands respectively. Bisulfite DNA sequencing of prakriti specific multiple CpG sites in promoters and 5'-UTR such as; LHX1 (Vata prakriti), SOX11 (Pitta prakriti) and CDH22 (Kapha prakriti) were validated. Kapha prakriti specific CDH22 5'-UTR CpG methylation was also found to be associated with higher body mass index (BMI). CONCLUSION: Differential DNA methylation signatures in three distinct prakriti phenotypes demonstrate the epigenetic basis of Indian traditional human classification which may have relevance to personalized medicine.
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Metilação de DNA , Ayurveda , Adulto , Cromatografia Líquida de Alta Pressão , Ilhas de CpG , DNA/química , Epigênese Genética , Genômica , Humanos , Imunoprecipitação , Índia , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Medicina de Precisão , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Adulto JovemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Melicope lunu-ankenda leaves are used to treat diabetes in folklore medicinal practices in India and Malaysia. Here we report the isolation of an O-prenylated flavonoid (3,5,4'-trihydroxy-8,3'-dimethoxy-7-(3-methylbut-2-enoxy)flavone; OPF) from the leaves of M. lunu-ankenda and its antidiabetes activity against type-2 diabetes mellitus (T2DM). MATERIALS AND METHODS: OPF was isolated from M. lunu-ankenda leaves by extraction and repeated column chromatography and its structure was elucidated by IR, UV-vis, 1D-, 2D-NMR and mass spectral analyses. Blood glucose lowering activity of OPF was tested in normal rats by oral glucose tolerance test and its efficacy was tested in STZ-induced type-2 diabetic rats. SGOT, SGPT, ALP, serum urea, total triglycerides, total cholesterol and reduction in HDLC, protein and serum insulin levels in normal rats and STZ-induced type-2 diabetic rats were measured. Acute toxicity of OPF was tested at 500 mg/kg dose. Mechanism of antidiabetes action of OPF was elucidated by insulin release from RIN 5F cells. RESULTS: OPF isolated from M. lunu-ankenda showed significant blood glucose lowering activity in oral glucose tolerance test on overnight fasted, glucose loaded normal rats and the optimum activity was observed at a dose of 10mg/kg body weight. In neonatal streptozotocin (STZ) induced diabetic rats, the OPF treatment for 20 days significantly ameliorated the derailed blood glucose levels, liver glycogen and serum biological parameters including insulin to normal levels. OPF on acute toxicity evaluation did not show any conspicuous toxic symptoms even at a higher dose of 500 mg/kg body weight in mice. On evaluating the mechanism of antidiabetes action, it was observed that, OPF induced insulin release from cultured RIN 5F cells in vitro from which it was evident that the OPF acts on pancreatic ß-cells for insulin release thereby correcting the derailed blood glucose levels, serum biochemical parameters and ameliorate various diabetic complications in STZ-induced diabetic rats. CONCLUSIONS: This study shows the potent antidiabetes activity of OPF and describes its mechanism of action. OPF is a promising candidate for the development of new generation anti-DM drugs. Isolation of the O-prenylated flavonoid justifies the use of M. lunu-ankenda for diabetic treatments in folklore practices.
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Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Flavonoides/uso terapêutico , Hipoglicemiantes/uso terapêutico , Rutaceae , Animais , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Flavonoides/toxicidade , Glicogênio/metabolismo , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Folhas de Planta , Prenilação , Ratos Wistar , Testes de Toxicidade AgudaRESUMO
Surface sediment samples were collected from Chitrapuzha (Cochin) estuarine system to identify the natural and anthropogenic origin of organic matter. The distribution and sources of organic matter were assessed with the help of fatty acid and alkane biomarkers. Fatty acids ranging from C12 to C28 were identified and C16:0 was the most abundant fatty acid, which contributed between 23.5 % and 52.4 % to total fatty acids. The low levels of polyunsaturated fatty acids indicate the effective bacterial recycling of algal fatty acids during the whole settling and depositing process. Aliphatic hydrocarbons ranging from C12 to C33 were identified and the total concentration ranged from 7876 to 43,357 ng g(-1). The presence of unresolved complex mixtures and lower pristane to phytane ratios indicates the petroleum contamination in the study area.
Assuntos
Biomarcadores/análise , Monitoramento Ambiental/estatística & dados numéricos , Estuários , Sedimentos Geológicos/química , Rios , Poluentes Químicos da Água/análise , Alcanos/análise , Monitoramento Ambiental/métodos , Ácidos Graxos/análise , Hidrocarbonetos/análise , Índia , Petróleo/análiseRESUMO
Melicope denhamii leaf volatile oil was isolated by hydrodistillation, and twenty-six constituents comprising 95.95% of the leaf oil were characterised by gas chromatographic techniques. Sesquiterpenes, zierone (22.49%) and α-gurjunene (19.96%), were identified as the major components. M. denhamii leaf oil tested against Gram-positive and Gram-negative bacteria showed significant activity against Bacillus subtilis and Escherichia coli. Anticancer activity of M. denhamii leaf oil against Dalton's lymphoma ascites cells was assessed by trypan blue exclusion and MTT assays, and the oil showed significant cytotoxicity at CD50 of 12.2 µg/mL. Induction of apoptosis on DLA cells by M. denhamii leaf oil was confirmed by morphological observation, nuclear damage and comet assays.
Assuntos
Antibacterianos/química , Antineoplásicos Fitogênicos/química , Óleos Voláteis/química , Rutaceae/química , Sesquiterpenos/química , Animais , Antibacterianos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose , Linhagem Celular Tumoral , Camundongos , Testes de Sensibilidade Microbiana , Folhas de Planta/química , Óleos de Plantas/química , Sesquiterpenos/isolamento & purificaçãoRESUMO
BACKGROUND: Constitutional type of an individual or prakriti is the basic clinical denominator in Ayurveda, which defines physical, physiological, and psychological traits of an individual and is the template for individualized diet, lifestyle counseling, and treatment. The large number of phenotype description by prakriti determination is based on the knowledge and experience of the assessor, and hence subject to inherent variations and interpretations. OBJECTIVE: In this study we have attempted to relate dominant prakriti attribute to body mass index (BMI) of individuals by assessing an acceptable tool to provide the quantitative measure to the currently qualitative ayurvedic prakriti determination. MATERIALS AND METHODS: The study is cross sectional, multicentered, and prakriti assessment of a total of 3416 subjects was undertaken. Healthy male, nonsmoking, nonalcoholic volunteers between the age group of 20-30 were screened for their prakriti after obtaining written consent to participate in the study. The prakriti was determined on the phenotype description of ayurvedic texts and simultaneously by the use of a computer-aided prakriti assessment tool. Kappa statistical analysis was employed to validate the prakriti assessment and Chi-square, Cramer's V test to determine the relatedness in the dominant prakriti to various attributes. RESULTS: We found 80% concordance between ayurvedic physician and software in predicting the prakriti of an individual. The kappa value of 0.77 showed moderate agreement in prakriti assessment. We observed a significant correlations of dominant prakriti to place of birth and BMI with Chi-square, P < 0.01 (Cramer's V-value of 0.156 and 0.368, respectively). CONCLUSION: The present study attempts to integrate knowledge of traditional ayurvedic concepts with the contemporary science. We have demonstrated analysis of prakriti classification and its association with BMI and place of birth with the implications to one of the ways for human classification.
RESUMO
SETTING: Two districts of Tamil Nadu, India OBJECTIVES: To determine the proportion of household contacts aged <6 years of patients with tuberculosis (TB) with positive sputum microscopy results who initiated and completed isoniazid preventive treatment (IPT), and to determine reasons for non-initiation and non-completion of IPT. DESIGN: Household visits were conducted on a random sample of adult patients registered during January-June 2012 to identify household contacts aged <6 years. RESULTS: Among 271 children living with 691 index patients, 218 (80%) were evaluated and 9 (4%) were diagnosed with TB. Of 209 remaining contacts, 70 (33%) started IPT and 16 (22.9%) completed a full course of IPT. Of 139 contacts who did not start IPT, five developed TB disease. Reasons for non-initiation of IPT included no home visit by the field staff (19%) and no education about IPT (61%). Reasons for non-completion included isoniazid not provided (52%) and long duration of treatment (28%). CONCLUSION: This study shows that Revised National TB Programme guidance was not being followed and IPT implementation was poor. Poor IPT uptake represents a missed opportunity to prevent future TB cases. Provision of IPT may be improved through training, improved logistics and enhanced supervision and monitoring.