RESUMO
Protein-protein interactions are crucial for the entry of viruses into the cell. Understanding the mechanism of interactions is essential in studying human-virus association, developing new biologics and drug candidates, as well as viral infections and antiviral responses. Experimental methods to analyze human-virus protein-protein interactions based on protein sequence data are time-consuming and labor-intensive, so machine learning models are being developed to predict interactions and determine large-scale interactomes between species. The present work highlights the importance of sequence features in classifying interacting and non-interacting proteins from the protein sequence data. Higher dimensional amino acid sequence features such as Amino Acid Composition (AAC), Dipeptide Composition (DPC), Grouped Amino Acid Composition (GAAC), Pseudo-Amino Acid Composition (PAAC) etc., are extracted. Following feature extraction, three datasets were created: Dataset 1 contains all of the extracted features. While Datasets 2 and 3 contain the most relevant features obtained through dimensionality reduction. To analyze the importance of high-dimensional features and their participation in protein-protein interactions, a random forest classifier is trained on three datasets. With dimensionality reduction, the model exhibited exceptional accuracy, indicating that dimensionality reduction fails to capture the complexity of interactions and the underlying relationships between human and viral proteins. As a result of retaining high-dimensional features, it is possible to capture all the characteristics of protein-protein interactions that resemble host-pathogen associations, leading to the development of biologically meaningful models. Our proposed approach is a more realistic and comprehensive classification model, leading to deeper insights and better applications in virology and drug development.
Assuntos
Aminoácidos , Proteínas , Humanos , Proteínas/metabolismo , Aminoácidos/química , Aprendizado de Máquina , Sequência de Aminoácidos , Máquina de Vetores de SuporteRESUMO
Muscle-residing regulatory T cells (Tregs) control local tissue integrity and function. However, the molecular interface connecting Treg-based regulation with muscle function and regeneration remains largely unexplored. Here, we show that exercise fosters a stable induction of highly functional muscle-residing Tregs with increased expression of amphiregulin (Areg), EGFR, and ST2. Mechanistically, we find that mice lacking IL6Rα on T cells (TKO) harbor significant reductions in muscle Treg functionality and satellite and fibro-adipogenic progenitor cells, which are required for muscle regeneration. Using exercise and sarcopenia models, IL6Rα TKO mice demonstrate deficits in Tregs, their functional maturation, and a more pronounced decline in muscle mass. Muscle injury models indicate that IL6Rα TKO mice have significant disabilities in muscle regeneration. Treg gain of function restores impaired muscle repair in IL6Rα TKO mice. Of note, pharmacological IL6R blockade in WT mice phenocopies deficits in muscle function identified in IL6Rα TKO mice, thereby highlighting the clinical implications of the findings.
Assuntos
Músculo Esquelético , Linfócitos T Reguladores , Camundongos , Animais , Linfócitos T Reguladores/metabolismo , Músculo Esquelético/metabolismo , Transdução de Sinais , Adipogenia , Receptores de Interleucina-6/metabolismoRESUMO
Long non-coding-RNAs (lncRNAs) are an expanding set of cis-/trans-regulatory RNA genes that outnumber the protein-coding genes. Although being increasingly discovered, the functional role of the majority of lncRNAs in diverse biological conditions is undefined. Increasing evidence supports the critical role of lncRNAs in the emergence, regulation, and progression of various viral infections including influenza, hepatitis, coronavirus, and human immunodeficiency virus. Hence, the identification of signature lncRNAs would facilitate focused analysis of their functional roles accounting for their targets and regulatory mechanisms associated with infections. Towards this, we compiled 2803 lncRNAs identified to be modulated by 33 viral strains in various mammalian cell types and are provided through the resource named VirhostlncR (http://ciods.in/VirhostlncR/). The information on each of the viral strains, their multiplicity of infection, duration of infection, host cell name and cell types, fold change of lncRNA expression, and their specific identification methods are integrated into VirhostlncR. Based on the current datasets, we report 150 lncRNAs including differentiation antagonizing non-protein coding RNA (DANCR), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), maternally expressed gene 3 (MEG3), nuclear paraspeckle assembly transcript 1 (NEAT1), and plasmacytoma variant translocation 1 (PVT1) to be perturbed by two or more viruses. Analysis of viral protein interactions with human transcription factors (TFs) or TF-containing protein complexes identified that distinct viruses can transcriptionally regulate many of these lncRNAs through multiple protein complexes. Together, we believe that the current dataset will enable priority selection of lncRNAs for identification of their targets and serve as an effective platform for the analysis of noncoding RNA-mediated regulations in viral infections.
Assuntos
RNA Longo não Codificante , Viroses , Animais , Humanos , RNA Longo não Codificante/genética , Viroses/genética , Mamíferos/genética , Mamíferos/metabolismoRESUMO
Phytochemical investigation of the stem bark of Hopea parviflora resulted in the isolation of 9 compounds; which includes friedelin (1), friedelin-3ß-ol (2), (-)-ampelopsin A (3), (-)-É-viniferin (4), (-)-hopeaphenol (5), vaticaphenol A (6), 2,4,8-trihydroxyphenanthrene-2-O-glucoside (7), ellagic acid-3,3',4-trimethoxy-4'-O-α-L-rhamnopyranoside (8) and ß-sitosterol-ß-D-glucoside (9). Among them, compounds 1, 2, 6, 7, 8 and 9 are isolated for the first time from this species. Further, we evaluated the anti-inflammatory activity of compounds 4, 5, 6, 7 and 8. In this study, compound 8 inhibited the activity of proinflammatory mediators like NO, TNF-α, IL-6, 5-LOX and COX-2, also promoted the action of anti-inflammatory mediator like IL-10 via inhibition of the NF-κB pathway in LPS-stimulated RAW 264.7 macrophages.
Assuntos
Anti-Inflamatórios/farmacologia , Dipterocarpaceae , Ácido Elágico/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Dipterocarpaceae/química , Ácido Elágico/isolamento & purificação , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Camundongos , NF-kappa B , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Células RAW 264.7RESUMO
Promalabaricone B (PMB), an acylphenol was isolated from dichloromethane-soluble extract of the seeds of Myrisitica fatua Houtt. PMB exhibited significant inhibitory activity on α-glucosidase enzyme. The molecular docking and dynamics studies of PMB with human maltase-glucoamylase were performed. PMB exhibited an enhanced glucose uptake in L6 myotubes with 46.3% in 2.5 µM. Encouraged with these results; we investigated the molecular mechanism of PMB through the upregulation of AMPK. The results revealed that PMB promoted the glucose uptake in myocytes by stimulating the translocation and expression of GLUT4. From this, it is clear that PMB can acts as a potential therapeutic option for diabetes treatment, and its hypoglycaemic effect may be mediated by AMPK upregulation and induction of GLUT4 translocation.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Fibras Musculares Esqueléticas/metabolismo , Myristica/química , Fenóis/farmacologia , Sementes/química , Regulação para Cima/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Glicosilação/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fenóis/química , Fenóis/isolamento & purificação , Saccharomyces cerevisiae/enzimologia , Transdução de Sinais/efeitos dos fármacos , Suínos , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hopea ponga (Dennst.) Mabb. Is used in traditional herbal formulations for diabetes complications. The aim of this study is to evaluate the antidiabetic effect of extracts and compounds from H. ponga. MATERIALS AND METHODS: Silica gel column chromatography was performed to identify various chemical components of the plant extract. Different extracts of H. ponga and isolated compounds were screened for their antidiabetic effect by modulation of digestive enzymes and protein glycation. The effect of glucose uptake by the compounds and the pathways through which the compounds mediate the glucose uptake potential were confirmed by fluorescent microscopy, flow cytometry and western blot analysis. RESULTS: Acetone and ethanol extracts of the stem bark of Hopea ponga (Dennst.) Mabb. Afforded six resveratrol oligomers namely, E-resveratrol (1), (-)-ε-viniferin (2), (-)-α-viniferin (3), trihydroxyphenanthrene glucoside (THPG) (4), vaticaphenol A (5), (-)-hopeaphenol (6), along with four phytosterols. The structures were determined on the basis of spectroscopic analyses including nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry (HRMS) data. Compounds 1-5 and 7-10 were tested for their α-glucosidase, α-amylase and glycation inhibitiory activities. All the resveratrol oligomers (1-5) showed prominent α-glucosidase inhibition with IC50 values, 12.56⯱â¯1.00, 23.98⯱â¯1.11, 7.17⯱â¯1.10, 31.74⯱â¯0.42 and 16.95⯱â¯0.39⯵M, respectively. Molecular docking studies also supported the observed α-glucosidase inhibition. Compound 3 displayed IC50 values of 4.85⯱â¯0.06 and 27.10⯱â¯0.04⯵M in α-amylase and glycation inhibitory assays activity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed that the compounds 3 and 4 were found to be less toxic at a concentration of 100⯵M (<10%) and 25⯵M (<20%), respectively. The effect of glucose uptake performed by 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) in L6 myoblast were measured by fluorescent microscopy and flow cytometry. The compounds 3 and 4 showed 2-NBDG uptake of 49.6% and 38.8% respectively. By examining the molecular pathway through which the compounds elicit their glucose uptake potential, it was observed that both the compounds mainly act via AMPK pathway. CONCLUSION: This is the first report on the isolation of compounds from H. ponga. Altogether, the results of this study reveal the antidiabetic effects of H. ponga extracts and isolated compounds promoting traditional use of this plant in the treatment of diabetes.
Assuntos
Dipterocarpaceae/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Resveratrol/farmacologia , Acetona/química , Animais , Linhagem Celular , Diabetes Mellitus/tratamento farmacológico , Ensaios Enzimáticos , Etanol/química , Glicosilação/efeitos dos fármacos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Concentração Inibidora 50 , Medicina Tradicional/métodos , Simulação de Acoplamento Molecular , Estrutura Molecular , Mioblastos , Casca de Planta/química , Extratos Vegetais/química , Caules de Planta/química , Ratos , Resveratrol/química , Resveratrol/isolamento & purificação , Testes de Toxicidade , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , alfa-Amilases/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismoRESUMO
High density lipoprotein (HDL)-macrophage interactions have the potential to modulate macrophage function in a beneficial way to prevent the development of lipid-loaded foam cell formation in atherosclerosis. Although HDL is atheroprotective, it can become dysfunctional in chronic inflammatory conditions and increase cardiovascular risk. Here, we examined the effect of dysfunctional-HDL from patients with coronary artery disease, on macrophage function in comparison to functional-HDL from controls. Exposure of macrophages to dysfunctional-HDL for 24 h resulted significant increase in cellular oxidative stress, cholesterol, and cytotoxicity. It also stimulated mitochondrial membrane depolarization, DNA damage, apoptosis, and cleavage of poly (ADP-ribose) polymerase, which are characteristics of proapoptotic pathways. In contrast, functional-HDL treatment maintained cholesterol homeostasis, essential membrane potential, DNA integrity, and cell survival. These results demonstrate that HDL from coronary artery disease (CAD) patient promotes proatherogenic effects that in turn trigger macrophage apoptosis, an important feature in atherogenesis and thereby providing new insight in our understanding of the atherogenic mechanisms.
Assuntos
Apoptose , Colesterol/metabolismo , Doença das Coronárias/metabolismo , Dano ao DNA , Células Espumosas/metabolismo , Macrófagos/metabolismo , Estresse Oxidativo , Absorção Fisiológica , Adulto , Transporte Biológico , Sobrevivência Celular , Células Cultivadas , Ensaio Cometa , Doença das Coronárias/sangue , Doença das Coronárias/imunologia , Doença das Coronárias/patologia , Meios de Cultura Livres de Soro , Feminino , Células Espumosas/imunologia , Células Espumosas/patologia , Humanos , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Potencial da Membrana Mitocondrial , Pessoa de Meia-Idade , Poli(ADP-Ribose) Polimerases/metabolismo , Proteólise , Espécies Reativas de Oxigênio/metabolismoRESUMO
Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity.
Assuntos
Dexametasona/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Glucocorticoides/uso terapêutico , Incretinas/uso terapêutico , Inflamação/tratamento farmacológico , Obesidade/tratamento farmacológico , Animais , Peso Corporal/efeitos dos fármacos , Dexametasona/análogos & derivados , Metabolismo Energético/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Glucocorticoides/química , Glucose/metabolismo , Células HEK293 , Humanos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Incretinas/química , Inflamação/complicações , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/complicações , Obesidade/metabolismoRESUMO
Although high-density lipoprotein is atheroprotective, it can become dysfunctional in chronic inflammatory conditions and increase cardiovascular risk. We previously demonstrated that HDL from subjects with documented coronary artery disease is dysfunctional and is pro-oxidant/proinflammatory in macrophages. Here we examined the influence of dysfunctional/proinflammatory HDL (piHDL) on lipid accumulation in human macrophages, in comparison to functional HDL (nHDL). Exposure of macrophages to piHDL, in contrast to nHDL, resulted in oxidative stress and marked uptake of lipids from piHDL, leading to the formation of foam cell phenotype as noted by oil red O staining with concomitant increase in total cellular cholesterol content. Using western blotting, we identified that piHDL profoundly upregulated the expression of scavenger receptor CD36 and suppressed the expression of ABCG1 and SRB1 in macrophages, thereby facilitating cholesterol influx capacity of macrophages. We then identified that CD36 did not act alone, indeed it was activated in macrophages along with ERK/MAPK, in response to piHDL, which in turn led to lipid accumulation as well as proinflammatory response via activation of NFkB and subsequent release of proinflammatory markers-TNF-ά and MMP-9. These effects were confirmed using pharmacological inhibitors for either CD36 or ERK/MAPK. Furthermore, piHDL treatment moderately activated PPAR-γ and Nrf2, the known regulators of CD36 in macrophages, suggesting that the two forms of HDL differentially regulate CD36 expression. Taken together, the results demonstrate that a novel CD36-ERK/MAPK-dependent mechanism is involved in macrophage lipid accumulation by piHDL, there by revealing the importance of functional deficiency in HDL and its potential link to atherogenesis.
Assuntos
Antígenos de Neoplasias/biossíntese , Doença da Artéria Coronariana/sangue , Células Espumosas/metabolismo , Lipoproteínas HDL/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Tetraspaninas/biossíntese , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/biossíntese , Adulto , Doença da Artéria Coronariana/patologia , Feminino , Células Espumosas/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lipoproteínas HDL/sangue , Masculino , Metaloproteinase 9 da Matriz/biossíntese , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/metabolismo , PPAR gama/metabolismo , Receptores Depuradores Classe B/biossíntese , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A remote sensing technique has been developed to detect physiological condition of phytoplankton using in situ and moderate imaging spectroradiometer (MODIS)-Aqua data. The recurring massive mixed algal bloom of diatom and Noctiluca scintillans in the Northern Arabian Sea during winter-spring was used as test bed to study formation, growth and degradation of phytoplankton. The ratio of chlorophyll (chl) to particulate organic carbon (POC) was considered as an indicator of phytoplankton physiological condition and used for the approach development. Algal blooms represent the areas of new production, and therefore, knowledge of their degradation is important to the study microbial loop and export carbon flux. Relation of chl/POC ratio with bacterial abundance revealed Gaussian distribution. Bacteria were strongly correlated with POC, and hence, the latter which is available from satellite data could be used as a proxy for remote assessment of bacteria. Thresholds for active and degrading phytoplankton were determined using the ratio computed from the satellite data. The criteria were implemented on MODIS data to generate an image representing distribution of degrading algal bloom. Bacteria abundance data from two validation cruises during dinoflagellate and cyanobacteria bloom confirmed well match up of phytoplankton degradation information from the satellite. Comparison of environmental parameters during decay phase of dinoflagellate (N. scintillans bloom (winter) and Trichodesmium bloom (summer) revealed that degradation after active Trichodesmium bloom was more severe as compared to the N. scintillans. The present study also highlights the prediction capability of phytoplankton degradation using a time series of satellite retrieved chlorophyll/POC images.
Assuntos
Bactérias/crescimento & desenvolvimento , Monitoramento Ambiental/métodos , Eutrofização , Fitoplâncton/crescimento & desenvolvimento , Tecnologia de Sensoriamento Remoto/métodos , Água do Mar/microbiologia , Bactérias/isolamento & purificação , Biodegradação Ambiental , Ciclo do Carbono , Clorofila/análise , Diatomáceas/crescimento & desenvolvimento , Diatomáceas/fisiologia , Dinoflagellida/crescimento & desenvolvimento , Dinoflagellida/fisiologia , Oceano Índico , Fitoplâncton/fisiologia , Estações do Ano , Água do Mar/químicaRESUMO
OBJECTIVE: High-density lipoprotein is a heterogeneous class of lipoprotein with diverse antiatherogenic functions. However, these antiatherogenic properties of HDL can be compromised in atherosclerotic conditions. We have recently identified dysfunctionality in HDL even among healthy subjects, during systemic inflammation. This study was carried out with the objective of examining whether dysfunctional HDL is associated with pro-inflammatory proteins other than the acute phase proteins as reported earlier. METHODS: Serum HDL was isolated by three different methods-density gradient ultracentrifugation, PEG precipitation and electroelution. The antioxidant property of HDL was assessed as change in oxidation of LDL based on Dichloro-dihydro-fluorescein diacetate assay. HDL was subjected to gelatin zymography and western blot for assessment of MMP 9 activity. RESULTS: Dysfunctional HDL did not prevent the auto-oxidation of LDL. On the contrary the oxidation was enhanced. The zymogram data indicated enhanced MMP-9 activity selectively in dysfunctional HDL, irrespective of HDL isolation methods. This was confirmed by western blot of HDL probed with antibody specific to MMP 9. We also observed that dysfunctional HDL induced inflammatory response in monocyte/macrophages as evidenced by enhanced TNF-α and decreased IL-10 production. Further, invitro incubation of functional HDL with MMP-9 provided direct evidence for the association of MMP-9 with HDL and the role of MMP-9 in HDL dysfunction. CONCLUSION: A remarkable finding in the present study is the previously unrecognized association of MMP-9 with dysfunctional HDL and its proinflammatory property, indicating a novel molecular connection that can enhance the risk of cardiovascular disease in subjects with dysfunctional HDL.
Assuntos
Lipoproteínas HDL/sangue , Metaloproteinase 9 da Matriz/sangue , Adulto , Western Blotting , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/epidemiologia , Células Cultivadas , Centrifugação com Gradiente de Concentração , Precipitação Química , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Interleucina-10/biossíntese , Interleucina-10/genética , Lipoproteínas HDL/isolamento & purificação , Lipoproteínas HDL/fisiologia , Lipoproteínas LDL/sangue , Masculino , Metaloproteinase 9 da Matriz/isolamento & purificação , Pessoa de Meia-Idade , Monócitos/metabolismo , Oxirredução , Polietilenoglicóis , Mapeamento de Interação de Proteínas , Risco , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
Oxalis corniculata is well known for its medicinal properties like anti-inflammatory, digestive, diuretic, antibacterial, antiseptic etc. The present study focuses on the ability of O. corniculata to alleviate liver damage caused by over dose of paracetamol. Antioxidant activity of O. corniculata was evaluated using the free radical scavenging activity of 1, 1-diphenyl-2- picrylhydrazyl radicals, total anti oxidant capacity by phosphomolybdenum method and total phenolic content was also evaluated. The ethanolic extract of whole plant of O. corniculata (OC, 500 microg/mL, po) significantly reduced 1, 1-diphenyl-2- picrylhydrazyl radicals. This dose also caused significant reduction (62.67%) in malondialdehyde levels of murine hepatic tissues. The antioxidant capacity of OC was comparable to that of standard ascorbic acid and showed 53.5 microg of phenol/mg OC. Rats pre-treated with OC for 4 days showed significant reduction in the serum enzymes such as glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase, serum bilirubin and showed almost normal histological liver architecture of the treated groups compared to paracetamol induced hepatic damage group, indicating its hepatoprotective and antioxidant potential.
Assuntos
Antioxidantes/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Acetaminofen/toxicidade , Animais , Antioxidantes/química , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Etanol , Masculino , Camundongos , Fenóis/química , Fenóis/farmacologia , Fitoterapia , Extratos Vegetais/química , Folhas de Planta/química , Substâncias Protetoras , Ratos , Ratos WistarRESUMO
Cassia occidentalis Linn. mast cell degranulation at a dose of 250 mg/kg, showed dose dependent stabilizing activity towards human RBC, with is widely used in traditional medicine of India to treat a number of clinical conditions including allergy and inflammatory manifestations. In the present study anti-allergic, anti-inflammatory and anti-oxidant properties of C. occidentalis whole plant ethanolic extract (CO) was investigated. Effects of CO on rat mast cell degranulation inhibition and human red blood cell (HRBC) membrane stabilization were studied in vitro following standard methods. The anti lipidperoxidant effects of CO were also studied in vitro. Effect of CO on carrageenan-induced mouse paw oedema inhibition was also assessed. CO significantly decreased maximum protection of 80.8% at 15 microg/ml. The extract also caused significant reduction in malondialdehyde (MDA) levels of murine hepatic microsomes at 100 microg/ml (56%) and significantly reduced carrageenan induced inflammation in mice at a dose of 250 mg/kg. Results of the present study indicated that CO inhibited mast cell degranulation, stabilized HRBC membrane thereby alleviating immediate hypersensitivity besides showing anti oxidant activity.
Assuntos
Antialérgicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Liberação de Histamina/efeitos dos fármacos , Inflamação/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Senna/química , Animais , Antialérgicos/isolamento & purificação , Antialérgicos/toxicidade , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/toxicidade , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Carragenina/toxicidade , Avaliação Pré-Clínica de Medicamentos , Edema/induzido quimicamente , Edema/prevenção & controle , Membrana Eritrocítica/efeitos dos fármacos , Etanol , Humanos , Inflamação/induzido quimicamente , Masculino , Mastócitos/efeitos dos fármacos , Ayurveda , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plantas Medicinais/química , Ratos , Solventes , ÁguaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Drynaria quercifolia (L.) J. Smith (Polypodiaceae), has been widely used by ethnic groups of India to treat inflammation, rheumatism, headache, bone fracture, jaundice, etc. AIM OF THE STUDY: To evaluate the anti-inflammatory and analgesic properties of the ethanolic extract of rhizome of Drynaria quercifolia (DQ) and its phytochemical profile. MATERIALS AND METHODS: DQ was used to evaluate the anti-inflammatory and analgesic effects using carrageenan-induced paw oedema/cotton pellet-induced granuloma in Wistar rats and acetic acid-induced writhing/formalin-induced paw licking test in Swiss albino mice respectively. RESULTS: Oral administration of DQ produced significant inhibition of carrageenan-induced paw oedema and granuloma formation in rats, almost comparable to that caused by indomethacin. DQ significantly attenuated acute and delayed phases of formalin-induced pain and acetic acid-induced writhing episodes in mice. The analgesia was comparable to that produced by sodium salicylate and aspirin respectively. Phytochemical analysis gave positive tests for catechin, coumarins, flavonoids, phenolics, saponin, steroids, tannins, and triterpenes. The total phenolics in DQ was 244 mg/g and naringin content was 0.048%. CONCLUSION: The results suggest the presence of potent anti-inflammatory and analgesic principles in DQ that justifies its use for alleviating painful inflammatory conditions.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Polypodiaceae , Analgésicos/análise , Analgésicos/toxicidade , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/análise , Carragenina , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inflamação/induzido quimicamente , Camundongos , Dor/induzido quimicamente , Medição da Dor , Extratos Vegetais/toxicidade , Ratos , Ratos WistarRESUMO
INTRODUCTION: Roots of Ixora coccinea (Rubiaceae), and Rhinacanthus nasuta (Acanthaceae) and whole plants of Spilanthes ciliata (Asteraceae) are extensively used by tribal communities in South India to treat liver diseases. However, the veracity of these tribal claims has not been investigated scientifically using the liver toxin, aflatoxin. This study reports on the protective effects of these three herbal ethanolic extracts on the aflatoxin B1 (AFB1)-intoxicated livers of albino male Wistar rats. METHODS: Biochemical parameters, including serum hepatic enzymes (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase), were studied. Hepatic tissues were processed for assay of reduced glutathione (GSH) and histological alterations. RESULTS: Pre-treatment of the rats with oral administration of the plant ethanolic extracts, Ixora coccinea (IC), Rhinacanthus nasuta (RN), Spilanthes ciliata (SC), prior to AFB1 was found to provide significant protection against toxin-induced liver damage, determined 72 hours after the AFB1 challenge (1.5 mg/kg, intraperitoneally) as evidenced by a significant lowering of the activity of the serum enzymes and enhanced hepatic reduced GSH status. Pathological examination of the liver tissues supported the biochemical findings. The three plant extracts, IC, RN and SC, showed significant antilipid peroxidant effects in vitro. CONCLUSION: It was concluded that the hepatoprotective effects of the three plant extracts observed in this study might result from their potent antioxidative properties.
Assuntos
Aflatoxina B1/toxicidade , Hepatopatias/tratamento farmacológico , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Aflatoxina B1/farmacologia , Animais , Antioxidantes/metabolismo , Núcleo Celular/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Glutationa/metabolismo , Linfócitos/efeitos dos fármacos , Masculino , Venenos , Ratos , Ratos Wistar , Silimarina/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Sida acuta Burm. f. (Malvaceae) is used in Indian traditional medicine to treat liver disorders and is useful in treating nervous and urinary diseases and also disorders of the blood and bile. AIM OF THE STUDY: Evaluation of the hepatoprotective properties of the methanolic extract of the root of Sida acuta (SA) and the phytochemical analysis of SA. MATERIALS AND METHODS: The model of paracetamol-induced hepatotoxicity in Wistar rats, liver histopathological observations, hexobarbitone-induced narcosis and in vitro anti-lipid peroxidation studies were employed to assess the hepatoprotective efficacy of SA. Phytochemical assay of SA was conducted following standard protocols. RESULTS: Significant hepatoprotective effects were obtained against liver damage induced by paracetamol overdose as evident from decreased serum levels of glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, alkaline phosphatase and bilirubin in the SA treated groups (50, 100, 200mg/kg) compared to the intoxicated controls. The hepatoprotective effect was further verified by histopathology of the liver. Pretreatment with Sida acuta extract significantly shortened the duration of hexobarbitone-induced narcosis in mice indicating its hepatoprotective potential. Phytochemical studies confirmed the presence of the phenolic compound, ferulic acid in the root of Sida acuta, which accounts for the significant hepatoprotective effects observed in the present study. CONCLUSION: The present study thus provides a scientific rationale for the traditional use of this plant in the management of liver disorders.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ácidos Cumáricos/farmacologia , Fígado/efeitos dos fármacos , Malvaceae/química , Fitoterapia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Acetaminofen , Fosfatase Alcalina/sangue , Animais , Bilirrubina/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Ácidos Cumáricos/análise , Hexobarbital , Fígado/patologia , Masculino , Camundongos , Extratos Vegetais/química , Raízes de Plantas , Ratos , Ratos Wistar , Estupor/sangue , Estupor/tratamento farmacológico , Transaminases/sangueRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cyclea peltata (Lam.) Hook. f. & Thoms. (Menispermaceae), locally called 'Padathaali/Padakizhangu' is used in Ayurvedic medicine to treat peptic ulcer. AIM OF THE STUDY: To evaluate the gastric antisecretory and antiulcer activity of Cyclea peltata. MATERIALS AND METHODS: The ethanolic extract of Cyclea peltata root was used to evaluate its gastric antisecretory and antiulcer effect in the pylorus-ligated rat model and gastric lesions induced by ethanol or ethanol and indomethacin respectively in rats. The levels of gastric wall mucus, non-protein sulfhydryl groups (NP-SH), malondialdehyde, protein and catalase activity in the stomach samples of Cyclea peltata treated and control groups of rats were also quantified. RESULTS: The ethanolic extract of Cyclea peltata roots showed significant antisecretory activity as evidenced by decreased pepsin secretion, gastric juice volume and acid output in pylorus-ligated rats. Pretreatment with Cyclea peltata extract provided significant protection against the peptic ulceration caused by ethanol administered individually, or in combination with indomethacin. Our studies also revealed that pretreatment with Cyclea peltata significantly increased the gastric protein and catalase concentration of ethanol treated rats. Further, it showed significant gastroprotective effects on the stomach wall of ethanol or ethanol and indomethacin treated rats by decreasing malondialdehyde level, increasing the gastric wall mucus and non-protein sulfhydryl groups. CONCLUSION: The present findings demonstrate that Cyclea peltata ethanolic extract has potent antisecretory and antiulcer effects and justify the traditional/ethnic usage of this herb to treat peptic ulcers and consequent stomach ache.
Assuntos
Antiulcerosos/uso terapêutico , Cyclea , Mucosa Gástrica/efeitos dos fármacos , Úlcera Péptica/prevenção & controle , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Antiulcerosos/farmacologia , Catalase/metabolismo , Modelos Animais de Doenças , Etanol , Suco Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Indometacina , Masculino , Malondialdeído/metabolismo , Muco/metabolismo , Pepsina A/metabolismo , Extratos Vegetais/farmacologia , Raízes de Plantas , Proteínas/metabolismo , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Compostos de Sulfidrila/metabolismoRESUMO
Hexane, chloroform and aqueous extracts from Hemidesmus indicus and Ichnocarpus frutescens roots were evaluated for their antimicrobial activity. The chloroform extract of both plants showed antibacterial and antifungal activities against the tested organisms. Both the plants showed highest antibacterial and antifungal activity against Eschericia coli and Aspergillus flavus respectively. With increase in concentration of the extract a corresponding increase in diameter of inhibition vgme was observed. The roots of the common substitute of H.Indicus namely Ifrutescenspossess similar antimicrobial properties.
RESUMO
Hibiscus hispidissimus Griff. is used in tribal medicine of Kerala, the southern most state of India, to treat liver diseases. In the present study, the effect of the ethanolic extract of Hibiscus hispidissimus whole plant on paracetamol (PCM)-induced and carbon tetrachloride (CCl4)-induced liver damage in healthy Wistar albino rats was studied. The results showed that significant hepatoprotective effects were obtained against liver damage induced by PCM and CCl4 as evidenced by decreased levels of serum enzymes, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SAKP), serum bilirubin (SB) and an almost normal histological architecture of the liver of the treated groups compared to the toxin controls. The extract also showed significant antilipid peroxidant effects in vitro, besides exhibiting significant activity in quenching 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical, indicating its potent antioxidant effects.
Assuntos
Acetaminofen/toxicidade , Tetracloreto de Carbono/toxicidade , Etanol , Hibiscus/química , Hepatopatias/prevenção & controle , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Compostos de Bifenilo/farmacologia , Doença Hepática Induzida por Substâncias e Drogas , Sequestradores de Radicais Livres/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Hepatopatias/enzimologia , Hepatopatias/patologia , Masculino , Picratos/farmacologia , Ratos , Ratos WistarRESUMO
Silver fern (Pityrogramma calomelanos L.) is a terrestrial or lithophytic herbaceous fern used for ornamental and medicinal purposes. In its farina it produces the cytotoxic and anticancer compound dihydrochalcone. In vitro induction of apospory and apogamy, and direct field establishment of aposporous gametophytes and subsequent sporophyte development has been accomplished. Half-strength Murashige and Skoog (MS) medium with 3.33 microM N(6)-benzyladenine (BA) and 2.32 microM kinetin (Kn) showed earlier development and produced higher numbers of aposporous gametophytes than half-strength MS basal medium. Crozier explants developed higher numbers (mean value 29.2) of gametophytes, but were slower than frond explants (mean value 23.2). The gametophytes originated from the epidermal hairs progressed from uniseriate filamentous to cordate through bi-, tri- and multiseriate and spatulate stage with the development of antheridia. Reduction in the nutrient and sucrose concentrations in the media favoured apogamy. Sucrose-free 1/10 strength MS medium and agar plates developed a mean of 30.4 and 29.9 sporophytes, respectively in the light. The greenhouse-established gametophytes developed sporophytes. The established sporophytes ex vitro showed 95% survival rate. Apogamous sporophytes and the source plant showed the same chromosome numbers (2n=116). The established protocol accomplishes apogamy and apospory in silver fern, and the aposporous gametophytes can be used for genetic transformation and development of transgenic silver fern.