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1.
Environ Res ; 252(Pt 2): 118949, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38631472

RESUMO

Anthropogenic activities are leaving lots of chemical footprints on the soil. It alters the physiochemical characteristics of the soil thereby modifying the natural soil microbiome. The prevalence of antimicrobial-resistance microbes in polluted soil has gained attention due to its obvious public health risks. This study focused on assessing the prevalence and distribution of antibiotic-resistance genes in polluted soil ecosystems impacted by industrial enterprises in southern Russia. Metagenomic analysis was conducted on soil samples collected from polluted sites using various approaches, and the prevalence of antibiotic-resistance genes was investigated. The results revealed that efflux-encoding pump sequences were the most widely represented group of genes, while genes whose products replaced antibiotic targets were less represented. The level of soil contamination increased, and there was an increase in the total number of antibiotic-resistance genes in proteobacteria, but a decrease in actinobacteria. The study proposed an optimal mechanism for processing metagenomic data in polluted soil ecosystems, which involves mapping raw reads by the KMA method, followed by a detailed study of specific genes. The study's conclusions provide valuable insights into the prevalence and distribution of antibiotic-resistance genes in polluted soils and have been illustrated in heat maps.


Assuntos
Metais Pesados , Hidrocarbonetos Policíclicos Aromáticos , Microbiologia do Solo , Poluentes do Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Metais Pesados/análise , Metais Pesados/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Resistência Microbiana a Medicamentos/genética , Federação Russa , Metagenômica , Genes Bacterianos , Farmacorresistência Bacteriana/genética , Monitoramento Ambiental
2.
Molecules ; 28(22)2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-38005250

RESUMO

Flavopiridol is a flavone synthesized from the natural product rohitukine, which is derived from an Indian medicinal plant, namely Dysoxylum binectariferum Hiern. A deeper understanding of the biological mechanisms by which such molecules act may allow scientists to develop effective therapeutic strategies against a variety of life-threatening diseases, such as cancer, viruses, fungal infections, parasites, and neurodegenerative diseases. Mechanistic insight of flavopiridol reveals its potential for kinase inhibitory activity of CDKs (cyclin-dependent kinases) and other kinases, leading to the inhibition of various processes, including cell cycle progression, apoptosis, tumor proliferation, angiogenesis, tumor metastasis, and the inflammation process. The synthetic derivatives of flavopiridol have overcome a few demerits of its parent compound. Moreover, these derivatives have much improved CDK-inhibitory activity and therapeutic abilities for treating severe human diseases. It appears that flavopiridol has potential as a candidate for the formulation of an integrated strategy to combat and alleviate human diseases. This review article aims to unravel the potential therapeutic effectiveness of flavopiridol and its possible mechanism of action.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Quinases Ciclina-Dependentes , Fosforilação , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose
3.
Environ Geochem Health ; 45(12): 9435-9449, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36070110

RESUMO

Soil decontamination and restoration continue to be a key environmental concern around the globe. The degradation of soil resources due to the presence of potentially toxic elements (PTEs) has a substantial influence on agricultural production, food security, and human well-being, and as a result, urgent action is required. PTEs pollution is not a threat to the agroecosystems but also a serious concern to human health; thereby, it needs to be addressed timely and effectively. Hence, the development of improved and cost-effective procedures to remove PTEs from polluted soils is imperative. With this context in mind, current review is designed to distinctly envisage the PTEs removal potential by the single and binary applications of biochar (BC) and nanomaterials (NMs).2 Recently, BC, a product of high-temperature biomass pyrolysis with high specific surface area, porosity, and distinctive physical and chemical properties has become one of the most used and economic adsorbent materials. Also, biochar's application has generated interest in a variety of fields and environments as a modern approach against the era of urbanization, industrialization, and climate change. Likewise, several NMs including metals and their oxides, carbon materials, zeolites, and bimetallic-based NMs have been documented as having the potential to remediate PTEs-polluted environments. However, both techniques have their own set of advantages and disadvantages, therefore combining them can be a more effective strategy to address the growing concern over the rapid accumulation and release of PTEs into the environment.


Assuntos
Nanoestruturas , Poluentes do Solo , Humanos , Solo/química , Poluentes do Solo/análise , Carvão Vegetal/química
4.
Environ Geochem Health ; 45(12): 9303-9319, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36564666

RESUMO

The poultry industry is generating a significant amount of waste from chicken droppings that are abundant in microbes as well as macro- and micronutrients suitable for manure. It has the potential to improve the microbial activity and nutrient dynamics in the soil, ultimately improving soil fertility. The present study aimed to investigate the effect of chicken droppings manure (CDM) on the diversity of the soil microbiome in the free walking chicken's area located in Stefanidar, Rostov Region, Russia. The data obtained were compared with 16 s rRNA from control samples located not far from the chicken's free-walking area, but not in direct contact with the droppings. Effect of CDM on the physicochemical characteristics of the soil and changes in its microbial diversity were assessed by employing the metagenomic approaches and 16 s rRNA-based taxonomic assessment. The alpha and beta diversity indices revealed that the application of the CDM significantly improved the soil microbial diversity. The 16S taxonomical analysis confirmed Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes, and Planctomycetes as abundant bacterial phylum. It also revealed the increase in the total number of the individual operational taxonomic unit (OTU) species, a qualitative indicator of the rich microbial community. The alpha diversity confirmed that the significant species richness of the soil is associated with the CDM treatment. The increased OTUs represent the qualitative indicator of a community that has been studied up to the depth of 5-20 cm of the CDM treatment range. These findings suggested that CDM-mediated microbial richness are believed to confer the cycling of carbon, nitrogen, and sulfur, along with key soil enzymes such as dehydrogenases and catalase carbohydrate-active enzymes. Hence, the application of CDM could improve soil fertility by nutrient cycling caused by changes in soil microbial dynamics, and it could also be a cost-effective sustainable means of improving soil health.


Assuntos
Microbiota , Solo , Animais , Galinhas , Esterco , Aves Domésticas , Microbiologia do Solo , Bactérias/genética
5.
J Appl Microbiol ; 133(3): 1229-1244, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35598183

RESUMO

The use of surfactants in households and industries is inevitable and so is their discharge into the environment, especially into the water bodies as effluents. Being surface-active agents, their utilization is mostly seen in soaps, detergents, personal care products, emulsifiers, wetting agents, etc. Anionic surfactants are the most used class. These surfactants are responsible for the foam and froth in the water bodies and cause potential adverse effects to both biotic and abiotic components of the ecosystem. Surfactants are capable of penetrating the cell membrane and thus cause toxicity to living organisms. Accumulation of these compounds has been known to cause significant gill damage and loss of sight in fish. Alteration of physiological and biochemical parameters of water decreases the amount of dissolved oxygen and thus affecting the entire ecosystem. Microbes utilizing surfactants as substrates for energy form the basis of the biodegradation of these compounds. The main organisms for surfactant biodegradation, both in sewage and natural waters, are bacteria. Several Pseudomonas and Bacillus spp. have shown efficient degradation of anionic surfactants namely: sodium dodecyl sulphate (SDS), linear alkylbenzene sulphonate (LAS), sodium dodecylbenzenesulphonate (SDBS). Also, several microbial consortia constituting Alcaligenes spp., Citrobacter spp., etc. have shown efficacy in the degradation of surfactants. The biodegradation efficiency studies of these microbes/microbial consortia would be of immense help in formulating better solutions for the bioremediation of surfactants and help to reduce their potential environmental hazards.


Assuntos
Ecossistema , Tensoativos , Animais , Bactérias/metabolismo , Biodegradação Ambiental , Tensoativos/metabolismo , Água/metabolismo
6.
Molecules ; 27(6)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35335270

RESUMO

Antibiotic resistance is one of the major growing concerns for public health. Conventional antibiotics act on a few predefined targets and, with time, several bacteria have developed resistance against a large number of antibiotics. The WHO has suggested that antibiotic resistance is at a crisis stage and identification of new antibiotics and targets could be the only approach to bridge the gap. Filamentous Temperature Sensitive-Mutant Z (Fts-Z) is one of the promising and less explored antibiotic targets. It is a highly conserved protein and plays a key role in bacterial cell division by introducing a cytokinetic Z-ring formation. In the present article, the potential of over 165 cyanobacterial compounds with reported antibiotic activity against the catalytic core domain in the Fts-Z protein of the Bacillus subtilis was studied. The identified cyanobacterial compounds were screened using the GLIDE module of Maestro v-2019-2 followed by 100-ns molecular dynamics (MD) simulation. Ranking of the potential compound was performed using dock score and MMGBSA based free energy. The study reported that the docking score of aphanorphine (-6.010 Kcalmol-1) and alpha-dimorphecolic acid (ADMA) (-6.574 Kcalmol-1) showed significant role with respect to the reported potential inhibitor PC190723 (-4.135 Kcalmol-1). A 100 ns MD simulation infers that Fts-Z ADMA complex has a stable conformation throughout the progress of the simulation. Both the compounds, i.e., ADMA and Aphanorphine, were further considered for In-vitro validation by performing anti-bacterial studies against B. subtilis by agar well diffusion method. The results obtained through In-vitro studies confirm that ADMA, a small molecule of cyanobacterial origin, is a potential compound with an antibacterial activity that may act by inhibiting the novel target Fts-Z and could be a great drug candidate for antibiotic development.


Assuntos
Bacillus subtilis , Cianobactérias , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Cianobactérias/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas Mutantes/metabolismo
7.
Molecules ; 27(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35408611

RESUMO

The increase in the number of cases of type 2 diabetes mellitus (T2DM) and the complications associated with the side effects of chemical/synthetic drugs have raised concerns about the safety of the drugs. Hence, there is an urgent need to explore and identify natural bioactive compounds as alternative drugs. Protein tyrosine phosphatase 1B (PTP1B) functions as a negative regulator and is therefore considered as one of the key protein targets modulating insulin signaling and insulin resistance. This article deals with the screening of a database of polyphenols against PTP1B activity for the identification of a potential inhibitor. The research plan had two clear objectives. Under first objective, we conducted a quantitative structure-activity relationship analysis of flavonoids with PTP1B that revealed the strongest correlation (R2 = 93.25%) between the number of aromatic bonds (naro) and inhibitory concentrations (IC50) of PTP1B. The second objective emphasized the binding potential of the selected polyphenols against the activity of PTP1B using molecular docking, molecular dynamic (MD) simulation and free energy estimation. Among all the polyphenols, silydianin, a flavonolignan, was identified as a lead compound that possesses drug-likeness properties, has a higher negative binding energy of -7.235 kcal/mol and a pKd value of 5.2. The free energy-based binding affinity (ΔG) was estimated to be -7.02 kcal/mol. MD simulation revealed the stability of interacting residues (Gly183, Arg221, Thr263 and Asp265). The results demonstrated that the identified polyphenol, silydianin, could act as a promising natural PTP1B inhibitor that can modulate the insulin resistance.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores Enzimáticos/química , Humanos , Simulação de Acoplamento Molecular , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Relação Quantitativa Estrutura-Atividade , Relação Estrutura-Atividade
8.
Ecotoxicology ; 28(5): 589-596, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31044329

RESUMO

Anthropogenic activity in East Antarctica has increased since the last 2-3 decades because of various scientific expeditions. Additionally, global pollution due to various newly introduced pollutants like pesticides is on use since the past century and many factors contribute to contamination even in Antarctica. During thirty fourth Indian Scientific Expedition to Antarctica (ISEA) in austral summer of 2014-2015, fifteen lake water samples were collected from five different lakes at Broknes peninsula, Larsemann Hills, East Antarctica. Persistent Organic Pollutants (POPs) residue levels found in lake water samples varied from 10.33-70.00 pg/mL in five different lakes. Presence of p,p'-DDT was detected in all different lakes but high concentration found in P4 lake water. After study confirms that Broknes peninsula in the Larsemann Hills area, East Antarctica has a trace amount of POPs which is an alarming situation and needs to be investigated further to maintain the pristine environment in Antarctica. The presence of POPs may be attributed to orographic effects, migratory birds, biomagnification and anthropogenic sources. In the future, new emerging pollutants must be analyzed like microplastics, phthalate, Paraxanthene etc.


Assuntos
Monitoramento Ambiental , Lagos/análise , Poluentes Químicos da Água/análise , Regiões Antárticas
9.
Microorganisms ; 12(6)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38930561

RESUMO

Currently, climate change-related environmental issues associated with agriculture is alarming and poses a potential risk to global food security, causing significant global concern as a result [...].

10.
J Agric Food Chem ; 72(1): 46-64, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38108272

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are highly toxic, persistent organic pollutants that threaten ecosystems and human health. Consistent monitoring is essential to minimize the entry of PAHs into plants and reduce food chain contamination. PAHs infiltrate plants through multiple pathways, causing detrimental effects and triggering diverse plant responses, ultimately increasing either toxicity or tolerance. Primary plant detoxification processes include enzymatic transformation, conjugation, and accumulation of contaminants in cell walls/vacuoles. Plants also play a crucial role in stimulating microbial PAHs degradation by producing root exudates, enhancing bioavailability, supplying nutrients, and promoting soil microbial diversity and activity. Thus, synergistic plant-microbe interactions efficiently decrease PAHs uptake by plants and, thereby, their accumulation along the food chain. This review highlights PAHs uptake pathways and their overall fate as contaminants of emerging concern (CEC). Understanding plant uptake mechanisms, responses to contaminants, and interactions with rhizosphere microbiota is vital for addressing PAH pollution in soil and ensuring food safety and quality.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Humanos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Solo , Ecossistema , Poluentes do Solo/metabolismo , Plantas/metabolismo , Biodegradação Ambiental
11.
Braz J Microbiol ; 55(2): 1507-1519, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38468117

RESUMO

Bioremediation of surfactants in water bodies holds significant ecological importance as they are contaminants of emerging concern posing substantial threats to the aquatic environment. Microbes exhibiting special ability in terms of bioremediation of contaminants have always been reported to thrive in extraordinary environmental conditions that can be extreme in terms of temperature, lack of nutrients, and salinity. Therefore, in the present investigation, a total of 46 bacterial isolates were isolated from the Indian sector of the Southern Ocean and screened for degradation of sodium dodecyl sulphate (SDS). Further, two Gram-positive psychrotolerant bacterial strains, ASOI-01 and ASOI-02 were identified with significant SDS degradation potential. These isolates were further studied for growth optimization under different environmental conditions. The strains were characterized as Staphylococcus saprophyticus and Bacillus pumilus based on morphological, biochemical, and molecular (16S RNA gene) characteristics. The study reports 88.9% and 93.4% degradation of SDS at a concentration of 100 mgL-1, at 20 °C, and pH 7 by S. saprophyticus ASOI-01 and B. pumilus ASOI-02, respectively. The experiments were also conducted in wastewater samples where a slight reduction in degradation efficiency was observed with strains ASOI-01 and ASOI-02 exhibiting 76.83 and 64.93% degradation of SDS respectively. This study infers that these bacteria can be used for the bioremediation of anionic surfactants from water bodies and establishes the potential of extremophilic microbes for the utilization of sustainable wastewater management.


Assuntos
Bacillus pumilus , Biodegradação Ambiental , Água do Mar , Dodecilsulfato de Sódio , Staphylococcus saprophyticus , Dodecilsulfato de Sódio/metabolismo , Bacillus pumilus/genética , Bacillus pumilus/metabolismo , Bacillus pumilus/isolamento & purificação , Bacillus pumilus/classificação , Staphylococcus saprophyticus/genética , Staphylococcus saprophyticus/isolamento & purificação , Staphylococcus saprophyticus/metabolismo , Staphylococcus saprophyticus/classificação , Água do Mar/microbiologia , Tensoativos/metabolismo , Filogenia , RNA Ribossômico 16S/genética , Poluentes Químicos da Água/metabolismo , Águas Residuárias/microbiologia
12.
Front Microbiol ; 15: 1403168, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741745

RESUMO

Overuse of antibiotics is accelerating the antimicrobial resistance among pathogenic microbes which is a growing public health challenge at the global level. Higher resistance causes severe infections, high complications, longer stays at hospitals and even increased mortality rates. Antimicrobial resistance (AMR) has a significant impact on national economies and their health systems, as it affects the productivity of patients or caregivers due to prolonged hospital stays with high economic costs. The main factor of AMR includes improper and excessive use of antimicrobials; lack of access to clean water, sanitation, and hygiene for humans and animals; poor infection prevention and control measures in hospitals; poor access to medicines and vaccines; lack of awareness and knowledge; and irregularities with legislation. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and animal health and the balance of the ecosystem. MDR bacteria such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp., and Klebsiella pneumonia can even cause death. These microorganisms use a variety of antibiotic resistance mechanisms, such as the development of drug-deactivating targets, alterations in antibiotic targets, or a decrease in intracellular antibiotic concentration, to render themselves resistant to numerous antibiotics. In context, the United Nations issued the Sustainable Development Goals (SDGs) in 2015 to serve as a worldwide blueprint for a better, more equal, and more sustainable existence on our planet. The SDGs place antimicrobial resistance (AMR) in the context of global public health and socioeconomic issues; also, the continued growth of AMR may hinder the achievement of numerous SDGs. In this review, we discuss the role of environmental pollution in the rise of AMR, different mechanisms underlying the antibiotic resistance, the threats posed by pathogenic microbes, novel antibiotics, strategies such as One Health to combat AMR, and the impact of resistance on sustainability and sustainable development goals.

13.
Pharmaceutics ; 15(2)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36840034

RESUMO

Due to rising incidence rates of liver cancer and worries about the toxicity of current chemotherapeutic medicines, the hunt for further alternative methods to treat this malignancy has escalated. Compared to chemotherapy, quercetin, a flavonoid, is relatively less harmful to normal cells and is regarded as an excellent free-radical scavenger. Apoptotic cell death of cancer cells caused by quercetin has been demonstrated by many prior studies. It is present in many fruits, vegetables, and herbs. Quercetin targets apoptosis, by upregulating Bax, caspase-3, and p21 while downregulating Akt, PLK-1, cyclin-B1, cyclin-A, CDC-2, CDK-2, and Bcl-2. Additionally, it has been reported to increase STAT3 protein degradation in liver cancer cells while decreasing STAT3 activation. Quercetin has a potential future in chemoprevention, based on substantial research on its anticancer effects. The current review discusses quercetin's mechanisms of action, nanodelivery strategies, and other potential cellular effects in liver cancer.

14.
Artigo em Inglês | MEDLINE | ID: mdl-37466886

RESUMO

The Yamuna River, a tributary of the holy Ganga, is heavily polluted in the Delhi-NCR region, India and has been gaining attention due to the excessive foaming of the river over the past few years. This can be directly or indirectly related to the overuse of surfactants and the discharge of untreated domestic and textile wastewater into the river. To determine the surfactant load and investigate potential surfactant-degrading bacteria in the region, 96 water samples from four sites in the Okhla Barrage stretch of the river were collected and analysed. The results showed that the selected sites have surfactant concentrations more than the permissible limit (1.00 mgL-1). Also, at most of the sites, the concentration crossed the desirable limit of BIS (0.2 mgL-1) during the period of analysis. The concentration of anionic surfactant reported in the region was found in the range of 0.29 mgL-1 and 2.83 mgL-1. A total of 38 different bacteria were isolated using selective media from the same water samples, out of which 7 bacterial isolates were screened for sodium dodecyl sulphate (SDS) tolerance activity. Based on 16S rRNA gene sequencing, 2 species, namely Pseudomonas koreensis YRW-02 and Pseudomonas songnenensis YRW-05 have been identified and their degradation potential was assessed at different SDS concentrations. The results showed that our strains YRW-02 and YRW-05 degraded 78.29 and 69.24% of SDS respectively. Growth optimization was also performed at different substrate concentrations, pH, and temperature to investigate optimum degradation conditions. This study plays a significant role in assessing the surfactant load and also gives a promising background for future use in in-situ bioremediation experiments.

15.
Naunyn Schmiedebergs Arch Pharmacol ; 396(12): 3459-3481, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37522916

RESUMO

Diabetes mellitus (D.M.) is a common metabolic disorder caused mainly by combining two primary factors, which are (1) defects in insulin production by the pancreatic ß-cells and (2) responsiveness of insulin-sensitive tissues towards insulin. Despite the rapid advancement in medicine to suppress elevated blood glucose levels (hyperglycemia) and insulin resistance associated with this hazard, a demand has undoubtedly emerged to find more effective and curative dimensions in therapeutic approaches against D.M. The administration of diabetes treatment that emphasizes insulin production and sensitivity may result in unfavorable side effects, reduced adherence, and potential treatment ineffectiveness. Recent progressions in genome editing technologies, for instance, in zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR-Cas)-associated nucleases, have greatly influenced the gene editing technology from concepts to clinical practices. Improvements in genome editing technologies have also opened up the possibility to target and modify specific genome sequences in a cell directly. CRISPR/Cas9 has proven effective in utilizing ex vivo gene editing in embryonic stem cells and stem cells derived from patients. This application has facilitated the exploration of pancreatic beta-cell development and function. Furthermore, CRISPR/Cas9 enables the creation of innovative animal models for diabetes and assesses the effectiveness of different therapeutic strategies in treating the condition. We, therefore, present a critical review of the therapeutic approaches of the genome editing tool CRISPR-Cas9 in treating D.M., discussing the challenges and limitations of implementing this technology.


Assuntos
Sistemas CRISPR-Cas , Diabetes Mellitus , Animais , Humanos , Edição de Genes/métodos , Insulina , Diferenciação Celular , Diabetes Mellitus/genética , Diabetes Mellitus/terapia
16.
Biotechnol Genet Eng Rev ; : 1-23, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36641593

RESUMO

Prolonged insulin resistance is considered one of the reasons for Type 2 Diabetes Mellitus. Upregulation of Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signalling, has been well studied as a key regulator in prognosis to insulin resistance. It has been widely studied as a desirable molecular therapeutic target. The study aimed to evaluate the efficacy of leaf extract of the medicinal plants Silybum marianum on the inhibition of PTP1B activity. It also explored the synergistic effect with extracts of Gymnema sylvestre (leaves), Momordica charantia (seeds), and Trigonella foenum graecum (seeds). The S. marianum leaves showed dose-dependent inhibition of PTP1B ranging from 9.48-47.95% (25-1000 µg mL-1). Assay with individual plant extracts showed comparatively lesser inhibition of PTP1B as compared to metformin as a control (38% inhibition). However, a synergistic effect showed nearly 45% PTP1B inhibition (higher than metformin) after the assay was done with selected four plant extracts in combination. The effect of leaf extracts of S. marianum was studied for glucose uptake efficiency in yeast cell lines which was found to be increased by 23% as compared to the control (without extract). Metformin improves glucose upake by yeast cells by ~15-31%. GC-MS analysis revealed 23 phytochemicals, some of which possessed anti-diabetic properties. A dose-dependent increase in antioxidant activity of S. marianum leaves extracts was observed (40-53%). The findings of the study highlighted the presence of various phytochemicals in leaves extracts that are effective against PTP1B inhibition and may help in reinvigorating drug development.

17.
Biomed Res Int ; 2023: 1977602, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860811

RESUMO

RNA viruses have been the most destructive due to their transmissibility and lack of control measures. Developments of vaccines for RNA viruses are very tough or almost impossible as viruses are highly mutable. For the last few decades, most of the epidemic and pandemic viral diseases have wreaked huge devastation with innumerable fatalities. To combat this threat to mankind, plant-derived novel antiviral products may contribute as reliable alternatives. They are assumed to be nontoxic, less hazardous, and safe compounds that have been in uses in the beginning of human civilization. In this growing COVID-19 pandemic, the present review amalgamates and depicts the role of various plant products in curing viral diseases in humans.


Assuntos
COVID-19 , Magnoliopsida , Vírus de RNA , Humanos , Pandemias/prevenção & controle , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , RNA
18.
J Biomol Struct Dyn ; : 1-12, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37261797

RESUMO

Antibiotic-resistant Acinetobacter baumannii, is a common pathogen found in hospital settings and has become nosocomial due to its high infection-causing tendency amongst ICU patients. The present study explores the cyanocompoundswhich were capable to inhibit the Penicillin Binding Protein of A. baumannii through molecular docking, ADMET, and molecular dynamicssimulation strategy. A database having structural and origin details was generated for 85 bioactive compounds in MS Excel. The 3-D structures weredownloaded from the PubChem database and minimized. The receptor protein was minimized and validated for structure correctness. The database was screened against the penicillin-binding protein of A. baumannii through PyRx software. The top 5 compounds including the control molecule werefurther redocked to the receptor molecule through Autodock Vina software. The molecule pose having the highest affinity was further subjected to 100ns MD- simulation and simultaneously the in-vitro activity of the methanol extract and hexane extract was checked through agar well diffusion assay.Docking studies indicate Tolyporphine K to be a lead molecule which was further assessed through Molecular dynamics and MM/PBSA. The in-silicoresults suggested that the protein-ligand complex was found to be stable over the 100 ns trajectory with a binding free energy of -8.56 Kcalmol-1. Theligand did not induce any major structural conformation in the protein moiety and was largely stabilized by hydrophobic interactions. The bioactivityscore and ADME properties of the compounds were also calculated. The in-vitro agar well diffusion assay showed a moderate zone of inhibition of12.33mm. The results indicate that the compound Tolyporphin- K could be a potential inhibitor of penicillin-binding protein in A. baumannii. Yet furtherwork needs to be done to have a more concrete basis for the pathway of inhibition.Communicated by Ramaswamy H. Sarma.

20.
Appl Biochem Biotechnol ; 194(10): 4683-4701, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35819691

RESUMO

Insulin resistance (IR) is a condition of impaired response of cells towards insulin. It is marked by excessive blood glucose, dysregulated insulin signalling, altered pathways, damaged pancreatic ß-cells, metabolic disorders, etc. Chronic hyperglycemic conditions leads to type 2 diabetes mellitus (T2DM) which causes excess generation of highly reactive free radicals, causing oxidative stress, further leading to development and progression of complications like vascular dysfunction, damaged cellular proteins, and DNA. One of the causes for IR is dysregulation of protein tyrosine phosphatase 1B (PTP1B). Advancements in drug therapeutics have helped people manage IR by regulating PTP1B, however have been reported to cause side effects. Therefore, there is a growing interest on usage of phytochemical constituents having IR therapeutic properties and aiding to minimize these complications. Medicinal plants have not been utilized to their full potential as a therapeutic drug due to lack of knowledge of their active and effective chemical constituents, mode of action, regulation of IR parameters, and dosage of administration. This review highlights phytochemical constituents present in medicinal plants or spices, their potential effectiveness on proteins (PTP1B) regulating IR, and reported possible mechanism of action studied on in vitro models. The study gives current knowledge and future recommendations on the above aspects and is expected to be beneficial in developing herbal drug using these phytochemical constituents, either alone or in combination, for medication of IR and diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Medicamentos Sintéticos , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Insulina/metabolismo , Monoéster Fosfórico Hidrolases/uso terapêutico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Medicamentos Sintéticos/uso terapêutico
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