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Semecarpus anacardium L.f. has been commonly used in various traditional medicines from ancient times. The nuts have been described in Ayurveda medication systems to treat numerous clinical ailments. However, isolating phytochemical constituents from nuts remain challenging and exhibits cytotoxic effects on other cells. In this study, we have standardized procedures for isolating phytochemicals from the leaf extract. The ethyl acetate leaf extract selectively affects cancer cells in a dose-dependent manner (IC50: 0.57 µg/ml in MCF-7 cells) in various cancer cell lines and induces apoptosis in cancer cells. However, the non-malignant cells were relatively insensitive to the extract. Next, the incubation of the leaf extract induces cell cycle arrest and suppresses cancer cell migration in the cell culture model. Moreover, oral administration of extract significantly restored tumor growth in mice. Together, these observations suggest the anti-cancer activities of S. anacardium L.f. leaf potential for both in vitro and in vivo models.
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Antineoplásicos , Neoplasias , Semecarpus , Camundongos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Neoplasias/tratamento farmacológico , NozesRESUMO
Panchvalkal kwath (PK) is a bark formulation of five pharmacologically important plants, i.e., Ficus benghalensis, Ficus racemosa, Ficus religiosa, Thespesia populnea, and Ficus lacor. The Ayurvedic formulation is being used since ancient times to cure diabetes, bacterial infections and heal wounds. The present study aims to identify the metabolite profiles of PK which could explain its properties and its mode of action against specific diseases and disorders. The aqueous extract of Panchvalkal is prepared through a hot maceration process. The extract is subjected to preliminary identification of phytoconstituents and FTIR spectroscopy to recognize functional groups. GC-MS analysis reveals that the extract is enriched with 24-Norursa-3,12-diene (25.16%); Lup-20(29)-en-3-one (16.76%); 2-methyl-3-(4-propan-2-ylphenyl) propanal (7.04%); 2-(hydroxymethyl)-2-nitropropane-1,3-diol (11.21%) and 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (4.15%). The presence of three new phytocompounds that are 4-(hydroxymethyl)-7-methyl-1,3-dioxepane-5,6-diol; 1-(4-isopropylphenyl)-2-methylpropylacetate and 4,4,6 A,6B,8A,11,11,14B-octamethyl-1,4,4A,5,6,6A,8,8a,910,11,12,12a,12b,13,14,14a,14b-ctadecahydro-3(2H)-picenone are detected in the extract. Metabolite profiles of the extract also constitute isoeugenol, stigmasterol, ergosterol, ocimene, myrcene, squalene, sphingosine, betulin, methyl ferulate and cis-jasmone, which are unraveled by 1 D 1H and 2 D 1H-13C HSQC NMR spectroscopy. This article focuses on the presence of different phytocompounds in PK in order to demonstrate its efficacy as a therapeutic formulation for a variety of diseases.
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Ficus , Extratos Vegetais , Extratos Vegetais/química , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Ergosterol , Ficus/químicaRESUMO
[This corrects the article DOI: 10.3389/fpls.2022.960717.].
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The global population is rising at an alarming rate, which is threatening food and nutritional security. Although chemical fertilizers and pesticides are important for achieving food security, their excessive usage critically affects soil health and adds up residues in the food chain. There is an increasing interest in identifying eco-friendly farm inputs that can improve crop productivity through sustainable agricultural practices. One of the most common approaches to reducing chemical inputs in agriculture is the use of plant growth regulators (PGRs). Here, we demonstrate the benefits of a natural and novel plant growth enhancer "calliterpenone," isolated from Callicarpa macrophylla, a medicinal plant, for increasing crop productivity in six crops, viz., rice, wheat, potato, tomato, chickpea, and onion. Results revealed that the application of calliterpenone (foliar spraying or seed soaking) enhanced the yield of rice (28.89%), onion (20.63%), potato (37.17%), tomato (28.36%), and chickpea (26.08%) at 0.001 mM and of wheat (27.23%) at 0.01 mM concentrations in comparison to control. This enhancement in yield was reflected through improvements in its growth attributes, viz., spike length, tillers plant-1, seeds spike-1, plant height, and biomass. Furthermore, the exogenous application of calliterpenone could increase the endogenous level of indole-3-acetic acid (IAA) in all tested crops and decrease the content of abscisic acid (ABA) in a few. Trials conducted at farmers' fields showed an overall ~12% increase in rice yield (mean of 11 farmers' fields ranging from 3.48 to 19.63%) and ~10% increase in wheat yield (ranging from 3.91 to 17.51%). The 0.001 mM of calliterpenone was the best effective dose for most crops except wheat, where a concentration of 0.01 mM was found to be the most optimal. This study indicates that calliterpenone is a natural plant growth promoter that can be used in boosting the yields of multiple crops and would be an important input component of organic farming.
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Picrorhiza kurrooa is an endangered medicinal herb which is distributed across the Himalayan region at an altitude between 3000-5000 m above mean sea level. The medicinal properties of P. kurrooa are attributed to monoterpenoid picrosides present in leaf, rhizome and root of the plant. However, no genomic information is currently available for P. kurrooa, which limits our understanding about its molecular systems and associated responses. The present study brings the first assembled draft genome of P. kurrooa by using 227 Gb of raw data generated by Illumina and PacBio RS II sequencing platforms. The assembled genome has a size of n = ~ 1.7 Gb with 12,924 scaffolds. Four pronged assembly quality validations studies, including experimentally reported ESTs mapping and directed sequencing of the assembled contigs, confirmed high reliability of the assembly. About 76% of the genome is covered by complex repeats alone. Annotation revealed 24,798 protein coding and 9789 non-coding genes. Using the assembled genome, a total of 710 miRNAs were discovered, many of which were found responsible for molecular response against temperature changes. The miRNAs and targets were validated experimentally. The availability of draft genome sequence will aid in genetic improvement and conservation of P. kurrooa. Also, this study provided an efficient approach for assembling complex genomes while dealing with repeats when regular assemblers failed to progress due to repeats.
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Mapeamento de Sequências Contíguas/métodos , Genoma de Planta , Picrorhiza/genética , Análise de Sequência de DNA/métodos , Espécies em Perigo de Extinção , Tamanho do Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Plantas Medicinais/genéticaRESUMO
Silicon (Si) is a beneficial macronutrient for plants. The Si supplementation to growth media mitigates abiotic and biotic stresses by regulating several physiological, biochemical and molecular mechanisms. The uptake of Si from the soil by root cells and subsequent transport are facilitated by Lsi1 (Low silicon1) belonging to nodulin 26-like major intrinsic protein (NIP) subfamily of aquaporin protein family, and Lsi2 (Low silicon 2) belonging to putative anion transporters, respectively. The soluble Si in the cytosol enhances the production of jasmonic acid, enzymatic and non-enzymatic antioxidants, secondary metabolites and induces expression of genes in plants under stress conditions. Silicon has been found beneficial in conferring tolerance against biotic and abiotic stresses by scavenging the reactive oxygen species (ROS) and regulation of different metabolic pathways. In the present review, Si transporters identified in various plant species and mechanisms of Si-mediated abiotic and biotic stress tolerance have been presented. In addition, role of Si in regulating gene expression under various abiotic and biotic stresses as revealed by transcriptome level studies has been discussed. This provides a deeper understanding of various mechanisms of Si-mediated stress tolerance in plants and may help in devising strategies for stress resilient agriculture.
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Plantas , Silício , Agricultura , Transporte Biológico , Silício/farmacologia , Estresse FisiológicoRESUMO
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged to be the greatest threat to humanity in the modern world and has claimed nearly 2.2 million lives worldwide. The United States alone accounts for more than one fourth of 100 million COVID-19 cases across the globe. Although vaccination against SARS-CoV-2 has begun, its efficacy in preventing a new or repeat COVID-19 infection in immunized individuals is yet to be determined. Calls for repurposing of existing, approved, drugs that target the inflammatory condition in COVID-19 are growing. Our initial gene ontology analysis predicts a similarity between SARS-CoV-2 induced inflammatory and immune dysregulation and the pathophysiology of rheumatoid arthritis. Interestingly, many of the drugs related to rheumatoid arthritis have been found to be lifesaving and contribute to lower COVID-19 morbidity. We also performed in silico investigation of binding of epigallocatechin gallate (EGCG), a well-known catechin, and other catechins on viral proteins and identified papain-like protease protein (PLPro) as a binding partner. Catechins bind to the S1 ubiquitin-binding site of PLPro, which might inhibit its protease function and abrogate SARS-CoV-2 inhibitory function on ubiquitin proteasome system and interferon stimulated gene system. In the realms of addressing inflammation and how to effectively target SARS-CoV-2 mediated respiratory distress syndrome, we review in this article the available knowledge on the strategic placement of EGCG in curbing inflammatory signals and how it may serve as a broad spectrum therapeutic in asymptomatic and symptomatic COVID-19 patients.
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Antivirais , Tratamento Farmacológico da COVID-19 , Catequina/análogos & derivados , Proteases 3C de Coronavírus , Inibidores de Cisteína Proteinase , SARS-CoV-2/enzimologia , Chá/química , Antivirais/química , Antivirais/uso terapêutico , Sítios de Ligação , COVID-19/enzimologia , COVID-19/epidemiologia , Catequina/química , Catequina/uso terapêutico , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/química , Inibidores de Cisteína Proteinase/química , Inibidores de Cisteína Proteinase/uso terapêutico , HumanosRESUMO
Strains of genus Pectobacterium are major cause of soft rot diseases in fruits and vegetables worldwide. Traditional control methods have not been very successful in combating the pathogenesis. As a result there has been an emerging need for developing an alternative ecofriendly and economical strategy. The pathogenesis of Pectobacterium sp. is mediated by quorum sensing (QS) and approaches based on inhibition of QS system to shut down the virulence genes without affecting growth of the pathogen may serve the purpose. Bacillus sp. OA10 associated with purple sponge Haliclona sp. was found to possess extracellular quorum quenching activity. The OA10 extract inhibited QS dependent virulence of Pectobacterium carotovorum subsp. carotovorum BR1 (PccBR1) at low concentrations (0.2 mg) as evident from 77.56 ± 6.17% reduction in potato maceration with complete inhibition by 0.8 mg. Inhibition of plant cell wall degrading enzymes (PCWDE) and carbapenem production by PccBR1 in presence of OA10 extract indicated disruption of the two QS pathways ExpI/ExpR and CarI/CarR in PccBR1. Bacillus sp. OA10 was not found to degrade acyl homoserine lactone (AHL), instead exhibited QSI activity by probably inhibiting AHL synthesis in PccBR1. Absence of enzymatic principle in quorum sensing inhibitor (QSI) is beneficial as enzymes may get inhibited by various factors during their application. OA10 extract did not affect growth of PccBR1, thereby reducing the chance of developing resistance against the QSI. Thus, Bacillus sp. OA10 can prove to be a good prospective candidate for QSI based novel biocontrol formulations.
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Bacillus/metabolismo , Pectobacterium carotovorum/metabolismo , Poríferos/microbiologia , Percepção de Quorum/efeitos dos fármacos , Doenças dos Animais/microbiologia , Animais , Antibacterianos/farmacologia , Biodegradação Ambiental , Técnicas de Cocultura , Meios de Cultura/química , Estudos Prospectivos , Solanum tuberosum , Virulência/efeitos dos fármacosRESUMO
Present study was aimed to investigate the antibacterial activity, bactericidal mechanism of action, killing kinetics and anti-inflammatory activity of Isodon melissoides (Benth.) H. Hara essential oil. The gas chromatography-flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of carvacrol (45.4%), p-cymene (11.6%) and thymol (11.3%) as major constituents of the oil. The oil displayed broad spectrum significant antibacterial activity (MIC: 0.13-8.33 ppm; MBC: 0.13->33.34 ppm) against test strains. The oil exhibited a time and dose-dependent bactericidal effect. The oil disrupted the cell membrane by changing the cell membrane permeability. The essential oil significantly decreased the overproduction of proinflammatory cytokines in LPS-induced inflammation in HaCaT cells without any cytotoxic effect. I. melissoides essential oil can be a promising alternative antimicrobial agent for the control of methicillin resistant staphylococci and other pathogenic bacteria tested, and also useful for the topical anti-inflammatory properties.
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Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Isodon/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Bactérias/efeitos dos fármacos , Cimenos/farmacologia , DNA/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Células HaCaT , Humanos , Cinética , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , RNA/metabolismo , Timol/farmacologiaRESUMO
In the microbial world, bacteria are the most effective agents in petroleum hydrocarbons (PHs) degradation, utilization/mineralization and they serve as essential degraders of crude oil contaminated environment. Some genes and traits are involved in the hydrocarbon utilization process for which transcriptome analyses are important to identify differentially expressed genes (DEGs) among different conditions, leading to a new understanding of genes or pathways associated with crude oil degradation. In this work, three crude oil utilizing Pseudomonas aeruginosa strains designated as N002, TP16 and J001 subjected to transcriptome analyses revealed a total of 81, 269 and 137 significant DEGs. Among them are 80 up-regulated genes and one downregulated gene of N002, 121 up- regulated and 148 down-regulated genes of TP16, 97 up-regulated and 40 down-regulated genes of J001 which are involved in various metabolic pathways. TP16 strain has shown more number of DEGs upon crude oil treatment in comparison to the other two strains. Through quantitative real time polymerase chain reaction (qRT-PCR), the selected DEGs of each strain from transcriptome data were substantiated. The results have shown that the up- regulated and down-regulated genes observed by qRT-PCR were consistent with transcriptome data. Taken together, our transcriptome results have revealed that TP16 is a potential P. aeruginosa strain for functional analysis of identified potential DEGs involved in crude oil degradation.
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Biodegradação Ambiental , Petróleo/microbiologia , Pseudomonas aeruginosa/genética , Bactérias/genética , Regulação para Baixo , Poluentes Ambientais/efeitos adversos , Perfilação da Expressão Gênica/métodos , Regulação Bacteriana da Expressão Gênica/genética , Hidrocarbonetos/metabolismo , Transcriptoma/genética , Regulação para CimaRESUMO
BACKGROUND: Amoora rohituka is described in Ayurveda, an Indian traditional system of medicine for management of disorders of blood, diseases of eye, helminthiasis disease, ulcer, liver disorders and splenomegaly. However, the leaves were not reported to have anticancer properties till date. OBJECTIVE: This study was carried out to evaluate the cytotoxic potential of leaf extracts of Amoora rohituka. MATERIALS AND METHODS: The leaves powder was macerated in petroleum ether, ethyl acetate and methanol and evaluated their anticancer activities in vitro. The phytochemical constituents of the active (ethyl acetate) extract were screened by FTIR analysis and phytochemical screening methods. RESULTS: The ethyl acetate extract (RLEA) showed the presence of alkaloids, flavonoids, steroids, tannins, saponins and terpenoids. The RLEA exhibited high cytotoxic effect against human breast cancer cells, MCF-7 (IC50 = 9.81 µg/mL) and induced apoptosis by altering nuclear morphology and DNA laddering. Wound healing assays explained the potency of extract to decrease the cell migration. CONCLUSION: The extract of Amoora rohituka leaves exhibited anticancer activity with less toxicity and it could be used for development of alternative drugs in the treatment of human breast cancer.
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Herbal drugs are used for the treatment of diseases and disorders with its less side effects, easy availability and low cost. Several bioactive compounds have been isolated from medicinal plants such as Ficus benghelensis, Ficus racemosa, Ficus religiosa, Thespesia populena and Ficus lacur bouch were taken for screening. This study aimed to evaluate molecular interactions of selected diabetes mellitus (DM) targets with bioactive compounds isolated from Ficus benghelensis, Ficus racemosa, Ficus religiosa, Thespesia populena and Ficus lacur bouch. In this article, screening of the best substances as bioactive compounds is achieved by molecular docking analysis with 3 best selected DM target proteins i.e., aldose reductase (AR), Insulin Receptor (IR) and Mono-ADP ribosyltransferase-sirtuin-6 (SIRT6). In this analysis six potential bioactive compounds (gossypetin, herbacetin, kaempferol, leucoperalgonidin, leucodelphinidin and sorbifolin) were successfully identified on the basis of binding energy (>8.0 kcal/mol) and dissociation constant using YASARA. Out of six compounds, herbacetin and sorbifolin were observed as most suitable ligands for management of diabetes mellitus.
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Thirty-two advanced pregnant multiparous Sahiwal cows were used to study the effect of additional zinc (Zn) and vitamin E (VE) supplementation on hormonal and biochemical changes. Cows were randomly assigned to four groups and fed a basal diet of compounded concentrate, berseem fodder, and wheat straw in a ratio of 60:20:20. The groups were: (1) the basal diet with no supplement (control treatment); (2) the basal diet supplemented with 60â¯mg/kg DM/cow daily of Zn (Zn treatment); (3) the basal diet supplemented with 1000â¯IU/cow daily of vitamin E (VE treatment); and (4) the basal diet supplemented with a combination of 60â¯mg Zn/kg DM/cow and 1000 IU vitamin E/cow/d (Znâ¯+â¯VE treatment). Blood samples were collected on -60, -45, -30, -15, -7, -3, 0, 3, 7, 15, 30, 45, 60, 90, and 120 d in relation to expected date of calving and were analyzed for endocrine variables and biochemical changes. Plasma concentrations of leptin, insulin, insulin like growth factor-1 (IGF-1), triidothyronine (T3), and tetraiodothyronine (T4) were decreased toward calving and observed lowest (Pâ¯<â¯0.05) on 3 d post-partum. However, plasma levels of growth hormone (GH) and cortisol increased toward calving and were found highest (Pâ¯<â¯0.05) on 3 d post-partum. Pre-partum concentrations of leptin and IGF-1 were higher (Pâ¯<â¯0.05) than its respective concentration observed during post-partum. Post-partum concentrations of GH and cortisol were higher (Pâ¯<â¯0.05) than its respective pre-partum concentration. Pre-partum concentrations of urea, triglycerides, Zn, and VE were higher (Pâ¯<â¯0.05) and total cholesterol and HDL cholesterol were lower than its values observed in post-partum among all the groups. Treatments had significant (Pâ¯<â¯0.05) effect on plasma hormonal levels and levels of Zn and VE but no effect on biochemical attributes. Cows fed on diet supplemented with Znâ¯+â¯VE had highest (Pâ¯<â¯0.05) pre as well as post-calving concentrations of leptin (6.38 vs 5.01â¯ng/ml), insulin (1.39 vs 1.33â¯ng/ml), GH (9.29 vs 13.72â¯ng/ml), IGF-1 (14.55 vs 12.59 nmol/l), T3 (1.45 vs 1.40â¯ng/ml), T4 (32.44 vs 31.79â¯ng/ml) whereas as lowest concentration of cortisol hormone (3.05 vs 3.44â¯ng/ml). Cows supplemented with combination of Zn and VE showed minimum decline in plasma concentration of leptin, insulin, GH, IGF-1, T3, and T4, and minimum increase in cortisol concentration. In conclusion, dairy cows around parturition faces various endocrine and biochemical alterations and supplementation of Zn in combination with VE can ameliorate adverse effect of calving stress by maintaining circulatory concentration of hormone and biochemicals towards the basal levels.
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Período Pós-Parto/efeitos dos fármacos , Vitamina E/farmacologia , Zinco/farmacologia , Animais , Bovinos , Suplementos Nutricionais , Sistema Endócrino/efeitos dos fármacos , Feminino , Fator de Crescimento Insulin-Like I/metabolismo , Gravidez , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1ß signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1ß signaling pathway, we found all the tested catechins could inhibit TAK-1 activity. Therefore, the consumption of green tea offers an overall anti-inflammatory effect. Molecular docking analysis confirms that EGCG, EGC, and EC all occupy the active site of the TAK1 kinase domain. However, EGCG occupies the majority of the TAK1 active site. In addition to TAK1 inhibition, EGCG can also inhibit P38 and nuclear NF-κB expression whereas EC and EGC were not effective inhibitors. Our findings suggest one of the main health benefits associated with the consumption of green tea are due to the activity of EGCG and EGC which are both present at higher amounts. Although EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered by the presence of EC. Therefore, varying EC content in green tea may reduce the anti-inflammatory effects of other potential catechins in green tea.
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Anti-Inflamatórios/farmacologia , Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Catequina/análogos & derivados , Fibroblastos/efeitos dos fármacos , Interleucina-1beta/farmacologia , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Chá/química , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antirreumáticos/química , Antirreumáticos/isolamento & purificação , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Domínio Catalítico , Catequina/química , Catequina/isolamento & purificação , Catequina/farmacologia , Células Cultivadas , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Fibroblastos/imunologia , Fibroblastos/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/química , MAP Quinase Quinase Quinases/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Fosforilação , Fitoterapia , Plantas Medicinais , Ligação Proteica , Inibidores de Proteínas Quinases/isolamento & purificação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Membrana Sinovial/imunologia , Membrana Sinovial/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
To unravel the molecular mechanism of defense against blister blight (BB) disease caused by an obligate biotrophic fungus, Exobasidium vexans, transcriptome of BB interaction with resistance and susceptible tea genotypes was analysed through RNA-seq using Illumina GAIIx at four different stages during ~20-day disease cycle. Approximately 69 million high quality reads were assembled de novo, yielding 37,790 unique transcripts with more than 55% being functionally annotated. Differentially expressed, 149 defense related transcripts/genes, namely defense related enzymes, resistance genes, multidrug resistant transporters, transcription factors, retrotransposons, metacaspases and chaperons were observed in RG, suggesting their role in defending against BB. Being present in the major hub, putative master regulators among these candidates were identified from predetermined protein-protein interaction network of Arabidopsis thaliana. Further, confirmation of abundant expression of well-known RPM1, RPS2 and RPP13 in quantitative Real Time PCR indicates salicylic acid and jasmonic acid, possibly induce synthesis of antimicrobial compounds, required to overcome the virulence of E. vexans. Compendiously, the current study provides a comprehensive gene expression and insights into the molecular mechanism of tea defense against BB to serve as a resource for unravelling the possible regulatory mechanism of immunity against various biotic stresses in tea and other crops.
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Camellia sinensis/genética , Camellia sinensis/microbiologia , Resistência à Doença/genética , Perfilação da Expressão Gênica , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Transcriptoma , Camellia sinensis/metabolismo , Biologia Computacional/métodos , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno/genética , Anotação de Sequência MolecularRESUMO
OBJECTIVE: Transforming growth factor ß-activated kinase 1 (TAK1) is a key MAPKKK family protein in interleukin-1ß (IL-1ß), tumor necrosis factor (TNF), and Toll-like receptor signaling. This study was undertaken to examine the posttranslational modification of TAK1 and its therapeutic regulation in rheumatoid arthritis (RA). METHODS: The effect of TAK1, IL-1 receptor-associated kinase 1 (IRAK-1), and TNF receptor-associated factor 6 (TRAF6) inhibition was evaluated in IL-1ß-stimulated human RA synovial fibroblasts (RASFs). Western blotting, immunoprecipitation, and 20S proteasome assay were used to study the ubiquitination process in RASFs. The efficacy of epigallocatechin-3-gallate (EGCG), a potent antiinflammatory molecule, in regulating these processes in RASFs was evaluated. Molecular docking was performed to examine the interaction of EGCG with human TAK1, IRAK-1, and TRAF6. These findings were confirmed using a rat model of adjuvant-induced arthritis (AIA). RESULTS: Inhibition of TAK1, but not IRAK-1 or TRAF6, completely abrogated IL-1ß-induced IL-6 and IL-8 synthesis in RASFs. EGCG inhibited TAK1 phosphorylation at Thr(184/187) and occupied the C(174) position, an ATP-binding site, to inhibit its kinase activity. EGCG pretreatment also inhibited K(63) -linked autoubiquitination of TRAF6, a posttranslational modification essential for TAK1 autophosphorylation, by forming a stable H bond at the K(124) position on TRAF6. Furthermore, EGCG enhanced proteasome-associated deubiquitinase expression to rescue proteins from proteasomal degradation. Western blot analyses of joint homogenates from rats with AIA showed a significant increase in K(48) -linked polyubiquitination, TAK1 phosphorylation, and TRAF6 expression when compared to naive rats. Administration of EGCG (50 mg/kg/day) for 10 days ameliorated AIA in rats by reducing TAK1 phosphorylation and K(48) -linked polyubiquitination. CONCLUSION: Our findings provide a rationale for targeting TAK1 for the treatment of RA with EGCG.
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Anti-Inflamatórios/farmacologia , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Catequina/análogos & derivados , Fibroblastos/efeitos dos fármacos , Interleucina-1beta/farmacologia , MAP Quinase Quinase Quinases/efeitos dos fármacos , Fator 6 Associado a Receptor de TNF/efeitos dos fármacos , Ubiquitinação/efeitos dos fármacos , Animais , Western Blotting , Catequina/farmacologia , Modelos Animais de Doenças , Feminino , Fibroblastos/metabolismo , Humanos , Imunoprecipitação , Técnicas In Vitro , Quinases Associadas a Receptores de Interleucina-1/efeitos dos fármacos , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Interleucina-6/metabolismo , Interleucina-8/efeitos dos fármacos , Interleucina-8/metabolismo , Lisina/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Simulação de Acoplamento Molecular , Complexo de Endopeptidases do Proteassoma , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew , Membrana Sinovial/citologia , Fator 6 Associado a Receptor de TNF/metabolismoRESUMO
Ayurveda involves the use of drugs obtained from plants, animals, and mineral origin. All the three sources of drugs can be divided under poisonous and nonpoisonous category. There are various crude drugs, which generally possess unwanted impurities and toxic substances, which can lead to harmful health problems. Many authors have reported that not all medicinal plants are safe to use since they can bear many toxic and harmful phytoconstituents in them. Sodhana (detoxification/purification) is the process, which involves the conversion of any poisonous drug into beneficial, nonpoisonous/nontoxic ones. Vatsanabha (Aconitum species), Semecarpus anacardium, Strychnos nux-vomica, Acorus calamus, Abrus precatorius etc., are some of the interesting examples of toxic plants, which are still used in the Indian system of medicine. Aconite, bhilawanols, strychnine, ß-asarone, abrin are some of the toxic components present in these plants and are relatively toxic in nature. Sodhana process involves the purification as well as reduction in the levels of toxic principles which sometimes results in an enhanced therapeutic efficacy. The present review is designed to extensively discuss and understand the scientific basis of the alternative use of toxic plants as a medicine after their purification process.
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The present research work reports the whole genome sequence analysis of Pseudomonas aeruginosa strain N002 isolated from crude oil contaminated soil of Assam, India having high crude oil degradation ability. The whole genome of the strain N002 was sequenced by shotgun sequencing using Ion Torrent method and complete genome sequence analysis was done. It was found that the strain N002 revealed versatility for degradation, emulsification and metabolizing of crude oil. Analysis of cluster of orthologous group (COG) revealed that N002 has significantly higher gene abundance for cell motility, lipid transport and metabolism, intracellular trafficking, secretion and vesicular transport, secondary metabolite biosynthesis, transport and catabolism, signal transduction mechanism and transcription than average levels found in other genome sequences of the same bacterial species. However, lower gene abundance for carbohydrate transport and metabolism, replication, recombination and repair, translation, ribosomal structure, biogenesis was observed in N002 than average levels of other bacterial species.
Assuntos
Genoma Bacteriano , Petróleo/metabolismo , Pseudomonas aeruginosa/genética , Sequência de Bases , Bases de Dados de Ácidos Nucleicos , Redes e Vias Metabólicas/genética , Dados de Sequência Molecular , Pseudomonas aeruginosa/metabolismo , Análise de Sequência de DNARESUMO
Superoxide dismutase (SOD) catalyzes the dismutation of superoxide radicals (O2( ·-)) to molecular oxygen (O2) and hydrogen peroxide (H2O2). Previously, we have identified and characterized a thermo-tolerant copper-zinc superoxide dismutase from Potentilla atrosanguinea (PaSOD), which retains its activity in the presence of NaCl. In the present study, we show that cotyledonary explants of PaSOD overexpressing transgenic Arabidopsis thaliana exhibit early callus induction and high shoot regenerative capacity than wild-type (WT) explants. Growth kinetic studies showed that transgenic lines have 2.6-3.3-folds higher growth rate of calli compared to WT. Regeneration frequency of calli developed from transgenic cotyledons was found to be 1.5-2.5-folds higher than that of WT explants on Murashige and Skoog medium supplemented with different concentrations of naphthalene acetic acid (NAA) and 6-benzylaminopurine (BAP) within 2 weeks. A positive regulatory effect of PaSOD and H2O2 was observed on different stages of callusing and regeneration. However, this effect was more pronounced at the early stages of the regeneration processes in transgenic lines as compared to WT. These results clearly indicate that plant regeneration is regulated by endogenous H2O2 and by factors, which enhance its accumulation. Transgenics also exhibited salt stress tolerance with higher SOD activity, chlorophyll content, total soluble sugars, and proline content, while lower ion leakage and less reduction in relative water content, as compared to WT. Thus, it appears that the activation of PaSOD at regeneration stage accompanied by increased H2O2 production can be one of the mechanisms controlling in vitro morphogenesis.
Assuntos
Arabidopsis/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteínas de Plantas/metabolismo , Brotos de Planta/metabolismo , Tolerância ao Sal/genética , Superóxido Dismutase/metabolismo , Plantas Geneticamente Modificadas/genética , Potentilla , RegeneraçãoRESUMO
Plants are used as medicine since ancient time, in organized (Ayurveda, Unani & Siddha) and unorganized (folk, native & tribal) form. In these systems, drugs are described either in Sanskrit or vernacular languages. Avartani (Helicteres isora Linn.) is a medicinal plant which is used in several diseases. It is commonly known as Marodphali, Marorphali, Enthani etc. due to screw like appearance of its fruit. Avartani is used as a folk medicine to treat snake bite, diarrhoea and constipation of new born baby. In the research, antioxidant, hypolipidaemic, antibacterial and antiplasmid activities, cardiac antioxidant, antiperoxidative potency, brain-antioxidation potency, anticancer activity, antinociceptive activity, hepatoprotective activity, anti-diarrheal activity and wormicidal activity in this plant were reviewed.