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Synthetic microbial communities, which simplify the complexity of natural ecosystems while retaining their key features, are gaining momentum in engineering and biotechnology applications. One potential application is the development of bioinoculants, offering an eco-friendly, sustainable solution to promote plant growth and increase resilience to abiotic stresses amidst climate change. A potential source for stress-tolerant microbes is those associated with desert plants, evolved and shaped by selective pressures to promote host health under harsh environmental conditions. In our research, we aim to design and develop synthetic microbial consortia inspired by the natural microbiota of four desert plants native to the Arabian Peninsula, inferred from our previous work identifying the structure and predicting the function of these microbial communities using high throughput eDNA barcoding. To obtain culturable microbes that are manageable and traceable yet still representative of natural microbial communities, we combined multiple experimental protocols coupled with compatibility and synergy assessments, along with in planta testing. We isolated a total of 75 bacteria and conducted detailed biological evaluations, revealing that an overwhelming majority (84 %) of all isolates produced indole acetic acid (IAA), with 73 % capable of solubilizing phosphate, 60 % producing siderophores, 47 % forming biofilms, and 35 % producing ACC deaminase, all contributing to plant growth and stress tolerance. We constructed four synthetic microbial consortia, named EcoBiomes, consisting of synergistic combinations of multiple species that can co-exist without significant antagonism. Our preliminary data indicate that EcoBiomes enhance the resilience of heterologous host plants under simulated environmental stresses, including drought, heat, and salinity. EcoBiomes offer a unique, sustainable, and eco-friendly solution to mitigate the impact of climate change on sensitive ecosystems, ultimately affecting global food security.
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BACKGROUND: Ficus benghalensis has been used by local health care practitioners to treat pain, inflammation, rheumatism, and other health issues. OBJECTIVE: In this study, the crude extract and diverse fractions, along with the isolated compound of F. benghalensis were examined for their roles as muscle relaxants, analgesics, and sedatives. METHODS: The extract and isolated compound 1 were screened for muscle-relaxant, analgesic, and sedative actions. The acetic acid-mediated writhing model was utilized for analgesic assessment, the muscle relaxant potential was quantified through traction and inclined plan tests, and the open field test was applied for sedative effects. RESULTS: The extract/fractions (25, 50, and 100 mg/kg) and isolated compounds (2.5, 5, 10, and 20 mg/kg) were tested at various doses. A profound (p< 0.001) reduce in the acetic acid-mediated writhing model was observed against carpachromene (64.44%), followed by ethyl acetate (60.67%) and methanol (58.42%) fractions. A marked (p< 0.001) muscle relaxant activity was noticed against the isolated compound (71.09%), followed by ethyl acetate (66.98%) and methanol (67.10%) fractions. Regarding the sedative effect, a significant action was noted against the isolated compound (71.09%), followed by ethyl acetate (66.98%) and methanol (67.10%) fractions. Furthermore, the binding modes of the isolated compounds were explored using molecular docking. The molecular docking study revealed that the isolated compound possessed good binding affinity for COX2 and GABA. Our isolated compound may possess inhibitory activity against COX2 and GABA receptors. CONCLUSION: The extract and isolated compounds of Ficus benghalensis can be used as analgesics, muscle relaxants, and sedatives. However, detailed molecular and functional analyses are essential to ascertain their function as muscle relaxants, analgesics, and sedatives.
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Pistacia chinensis is locally practiced for treating diabetes, pain, inflammation, and erectile dysfunction. Therefore, the current studies subjected the crude extract/fractions and the isolated compound (2-(3,4-dihydroxyphenyl)-7,8-dihydroxy-3-methoxy-4H-chromen-4-one) to α-glucosidase inhibitor and anti-glycation activities. The development of long-term complications associated with diabetes is primarily caused by chronic hyperglycemia. Regarding α-glucosidase, the most significant inhibitory effect was observed with compound 1 (93.09%), followed by the methanolic extract (80.87%) with IC50 values of 45.86 and 86.32 µM. The maximum anti-glycation potential was shown by an isolated compound 1 followed by methanolic extract with effect inhibition of 90.12 and 72.09, respectively. Compound 1 is expected to have the highest gastrointestinal absorption rate, with a predicted absorption rate of 86.156%. This indicates oral suitability. The compound 1 is expected to have no harmful effects on the liver. In addition, our docking results suggest that alpha-glucosidase and isolated compounds showed strong interaction with ILE821, GLN900, and ALA901 residues, along with a -11.95 docking score.
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Introduction: Desert ecosystems harbor a unique microbial diversity that is crucial for ecological stability and biogeochemical cycles. An in-depth understanding of the biodiversity, compositions, and functions of these microbial communities is imperative to navigate global changes and confront potential threats and opportunities applicable to agricultural ecosystems amid climate change. Methods: This study explores microbial communities in the rhizosphere and endosphere of desert plants native to the Arabian Peninsula using next-generation sequencing of the 16S rRNA gene (V3-V4 hypervariable region). Results: Our results reveal that each microbial community has a diverse and unique microbial composition. Based on alpha and beta diversity indices, the rhizosphere microbiome is significantly diverse and richer in microbial taxa compared to the endosphere. The data reveals a shift towards fast-growing microbes with active metabolism, involvement in nutrient cycling, nitrogen fixation, and defense pathways. Our data reveals the presence of habitat-specific microbial communities in the desert, highlighting their remarkable resilience and adaptability to extreme environmental conditions. Notably, we observed the existence of radiation-resistant microbes such as Deinococcus radiotolerans, Kocuria sp., and Rubrobacter radiotolerans which can tolerate high levels of ionizing radiation. Additionally, examples of microbes exhibiting tolerance to challenging conditions include Nocardioides halotolerans, thriving in high-salinity environments, and hyperthermophilic microbes such as Quasibacillus thermotolerans. Moreover, functional analysis reveals enrichment in chaperon biosynthesis pathways associated with correct protein folding under heat stress conditions. Discussion: Our research sheds light on the unique diversity of desert microbes and underscores their potential applications to increase the resilience of agriculture ecosystems, offering a promising strategy to fortify crops against the challenges posed by climate change, ultimately supporting sustainable food production for our ever-expanding global population.
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Reactive oxygen species (ROS) are produced under normal physiological conditions and may have beneficial and harmful effects on biological systems. ROS are involved in many physiological processes such as differentiation, proliferation, necrosis, autophagy, and apoptosis by acting as signaling molecules or regulators of transcription factors. In this case, maintaining proper cellular ROS levels is known as redox homeostasis. Oxidative stress occurs because of the imbalance between the production of ROS and antioxidant defenses. Sources of ROS include the mitochondria, auto-oxidation of glucose, and enzymatic pathways such as nicotinamide adenine dinucleotide phosphate reduced (NAD[P]H) oxidase. The possible ROS pathways are NF-κB, MAPKs, PI3K-Akt, and the Keap1-Nrf2-ARE signaling pathway. This review covers the literature pertaining to the possible ROS pathways and strategies to inhibit them. Additionally, this review summarizes the literature related to finding ROS inhibitors.
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In this work, we investigated Diospyros kaki extract and an isolated compound for their potential as xanthine oxidase (XO) inhibitors, a target enzyme involved in inflammatory disorders. The prepared extract was subjected to column chromatography, and dinaphthodiospyrol S was isolated. Then XO inhibitory properties were assessed using a spectrophotometry microplate reader. DMSO was taken as a negative control, and allopurinol was used as a standard drug. The molecular docking study of the isolated compound to the XO active site was performed, followed by visualization and protein-ligand interaction. The defatted chloroform extract showed the highest inhibitory effect, followed by the chloroform extract and the isolated compound. The isolated compound exhibited significant inhibitory activity against XO with an IC50 value of 1.09 µM. Molecular docking studies showed that the compound strongly interacts with XO, forming hydrogen bond interactions with Arg149 and Cys113 and H-pi interactions with Cys116 and Leu147. The binding score of -7.678 kcal/mol further supported the potential of the isolated compound as an XO inhibitor. The quantum chemical procedures were used to study the electronic behavior of dinaphthodiospyrol S isolated from D. kaki. Frontier molecular orbital (FMO) analysis was performed to understand the distribution of electronic density, highest occupied molecular orbital HOMO, lowest unoccupied molecular orbital LUMO, and energy gaps. The values of HOMO, LUMO, and energy gap were found to be -6.39, -3.51 and 2.88 eV respectively. The FMO results indicated the intramolecular charge transfer. Moreover, reactivity descriptors were also determined to confirm the stability of the compound. The molecular electrostatic potential (MEP) investigation was done to analyze the electrophilic and nucleophilic sites within a molecule. The oxygen atoms in the compound exhibited negative potential, indicating that they are favorable sites for electrophilic attacks. The results indicate its potential as a therapeutic agent for related disorders. Further studies are needed to investigate this compound's in vivo efficacy and safety as a potential drug candidate.
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Flavonoids effectively treat cancer, inflammatory disorders (cardiovascular and nervous systems), and oxidative stress. Fisetin, derived from fruits and vegetables, suppresses cancer growth by altering cell cycle parameters that lead to cell death and angiogenesis without affecting healthy cells. Clinical trials are needed in humans to prove the effectiveness of this treatment for a wide range of cancers. According to the results of this study, fisetin can be used to prevent and treat a variety of cancers. Despite early detection and treatment advances, cancer is the leading cause of death worldwide. We must take proactive steps to reduce the risk of cancer. The natural flavonoid fisetin has pharmacological properties that suppress cancer growth. This review focuses on the potential drug use of fisetin, which has been extensively explored for its cancer-fighting ability and other pharmacological activities such as diabetes, COVID-19, obesity, allergy, neurological, and bone disorders. Researchers have focused on the molecular function of fisetin. In this review, we have highlighted the biological activities against chronic disorders, including cancer, metabolic illnesses, and degenerative illnesses, of the dietary components of fisetin.
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COVID-19 , Neoplasias , Humanos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Flavonóis/farmacologia , Flavonóis/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , ApoptoseRESUMO
Metastasis accounts for the majority of cancer-associated mortalities, representing a huge health and economic burden. One of the mechanisms that enables metastasis is hypersialylation, characterized by an overabundance of sialylated glycans on the tumor surface, which leads to repulsion and detachment of cells from the original tumor. Once the tumor cells are mobilized, sialylated glycans hijack the natural killer T-cells through self-molecular mimicry and activatea downstream cascade of molecular events that result in inhibition of cytotoxicity and inflammatory responses against cancer cells, ultimately leading to immune evasion. Sialylation is mediated by a family of enzymes known as sialyltransferases (STs), which catalyse the transfer of sialic acid residue from the donor, CMP-sialic acid, onto the terminal end of an acceptor such as N-acetylgalactosamine on the cell-surface. Upregulation of STs increases tumor hypersialylation by up to 60% which is considered a distinctive hallmark of several types of cancers such as pancreatic, breast, and ovarian cancer. Therefore, inhibiting STs has emerged as a potential strategy to prevent metastasis. In this comprehensive review, we discuss the recent advances in designing novel sialyltransferase inhibitors using ligand-based drug design and high-throughput screening of natural and synthetic entities, emphasizing the most successful approaches. We analyse the limitations and challenges of designing selective, potent, and cell-permeable ST inhibitors that hindered further development of ST inhibitors into clinical trials. We conclude by analysing emerging opportunities, including advanced delivery methods which further increase the potential of these inhibitors to enrich the clinics with novel therapeutics to combat metastasis.
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Ácido N-Acetilneuramínico , Neoplasias , Humanos , Ácido N-Acetilneuramínico/uso terapêutico , Neoplasias/tratamento farmacológico , Ácido N-Acetilneuramínico do Monofosfato de Citidina , Polissacarídeos/uso terapêutico , SialiltransferasesRESUMO
Background: Artemether (ARM), the O-methyl ether prodrug of dihydroartemisinin (DHA), is considered a first-line antimalarial agent. Artemether is extensively metabolized in vivo to its active metabolite DHA, and therefore its determination offers considerable difficulties. In the present study, DHA identification and estimation were accurately performed by the mass spectrometric analysis, using a high-resolution liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) LTQ Orbitrap hybrid mass spectrometer. Methods: The plasma samples were taken from healthy volunteers, and the spiked plasma was extracted by adding 1 mL of a mixture of dichloromethane and tert.-methyl butyl ether (8:2 v/v) to 0.5 mL of plasma. The internal standard solution (artemisinin 500 ng/mL) was added to the plasma samples. After vertexing and centrifugation, the organic layer was separated and transferred into another tube and dried under nitrogen. The residue was reconstituted in 100 µL of acetonitrile and was injected onto the LC-MS system for analysis. Measurement of standards and samples was carried out isocratically on a Surveyor HPLC system combined with an LTQ Orbitrap mass spectrometer using an ACE 5 C18-PFP column. Mobile phase A consisted of 0.1% v/v formic acid in water, Mobile phase B consisted of acetonitrile only, and isocratic elution was carried out with A:B 20:80, v/v. The flow rate was 500 µL/min. The ESI interface was operated in a positive ion mode with a spray voltage of 4.5 kV. Results: Artemether is not a very biologically stable compound and is immediately metabolized to its active metabolite dihydroartemisinin, so no clear peak was observed for artemether. Both artemether and DHA after ionization undergo neutral losses of methanol and water, respectively, in the source of the mass spectrometer. The ions observed were (MH-H2O) m/z 267.15 for DHA and (MH-m/z 283.15 for internal standard artemisinin. The method was validated according to international guidelines. Discussion: The validated method was applied successfully for the determination and quantification of DHA in plasma samples. This method works well for the extraction of drugs, and the Orbitrap system with the help of Xcalibur software accurately and precisely determines the concentration of DHA in spiked as well as volunteer's plasma.
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The human body is a superorganism that harbors trillions of microbes, most of which inhabit the gut. To colonize our bodies, these microbes have evolved strategies to regulate the immune system and maintain intestinal immune homeostasis by secreting chemical mediators. There is much interest in deciphering these chemicals and furthering their development as novel therapeutics. In this work, we present a combined experimental and computational approach to identifying functional immunomodulatory molecules from the gut microbiome. Based on this approach, we report the discovery of lactomodulin, a unique peptide from Lactobacillus rhamnosus that exhibits dual anti-inflammatory and antibiotic activities and minimal cytotoxicity in human cell lines. Lactomodulin reduces several secreted proinflammatory cytokines, including IL-8, IL-6, IL-1ß, and TNF-α. As an antibiotic, lactomodulin is effective against a range of human pathogens, and is most potent against antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). The multifunctional activity of lactomodulin affirms that the microbiome encodes evolved functional molecules with promising therapeutic potential.
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Staphylococcus aureus Resistente à Meticilina , Microbiota , Humanos , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Peptídeos/farmacologia , Anti-Inflamatórios/farmacologiaRESUMO
Once the World Health Organization (WHO) declared the COVID-19 (Coronavirus Infectious Disease-19) outbreak to be pandemic, massive efforts have been launched by researchers around the globe to combat this emerging infectious disease. Strategies that must be investigated such as expanding testing capabilities, developing effective medicines, as well as developing safe and effective vaccines for COVID-19 disease that produce long-lasting immunity to human system. Now-a-days, bio-sensing, medication delivery, imaging, and antimicrobial treatment are just a few of the medical applications for nanoparticles (NPs). Since the early 1990s, nanoparticle drug delivery methods have been employed in clinical trials. Since then, the discipline of nanomedicine has evolved in tandem with expanding technological demands to better medicinal delivery. Newer generations of NPs have emerged in recent decades that are capable of performing additional delivery tasks, allowing for therapy via novel therapeutic modalities. Many of these next generation NPs and associated products have entered clinical trials and have been approved for diverse indications in the present clinical environment. For systemic applications, NPs or nanomedicine-based drug delivery systems have substantial benefits over their non-formulated and free drug counterparts. Nanoparticle systems, for example, are capable of delivering medicines and treating parts of the body that are inaccessible to existing delivery systems. As a result, NPs medication delivery is one of the most studied preclinical and clinical systems. NPs-based vaccines delivering SARS-CoV-2 antigens will play an increasingly important role in prolonging or improving COVID-19 vaccination outcomes. This review provides insights about employing NPs-based drug delivery systems for the treatment of COVID-19 to increase the bioavailability of current drugs, reducing their toxicity, and to increase their efficiency. This article also exhibits their capability and efficacy, and highlighting the future aspects and challenges on nanoparticle products in clinical trials of COVID-19.
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COVID-19 , Nanopartículas , COVID-19/terapia , Vacinas contra COVID-19 , Ensaios Clínicos como Assunto , Humanos , Nanopartículas/uso terapêuticoRESUMO
Plants including Rhizoma polgonati, Smilax china, and Trigonella foenum-graecum contain a lot of diosgenin, a steroidal sapogenin. This bioactive phytochemical has shown high potential and interest in the treatment of various disorders such as cancer, diabetes, arthritis, asthma, and cardiovascular disease, in addition to being an important starting material for the preparation of several steroidal drugs in the pharmaceutical industry. This review aims to provide an overview of the in vitro, in vivo, and clinical studies reporting the diosgenin's pharmacological effects and to discuss the safety issues. Preclinical studies have shown promising effects on cancer, neuroprotection, atherosclerosis, asthma, bone health, and other pathologies. Clinical investigations have demonstrated diosgenin's nontoxic nature and promising benefits on cognitive function and menopause. However, further well-designed clinical trials are needed to address the other effects seen in preclinical studies, as well as a better knowledge of the diosgenin's safety profile.
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Asma , Diosgenina , Neoplasias , Trigonella , Asma/tratamento farmacológico , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos , Extratos VegetaisRESUMO
Neuroinflammation, a protective response of the central nervous system (CNS), is associated with the pathogenesis of neurodegenerative diseases. The CNS is composed of neurons and glial cells consisting of microglia, oligodendrocytes, and astrocytes. Entry of any foreign pathogen activates the glial cells (astrocytes and microglia) and overactivation of these cells triggers the release of various neuroinflammatory markers (NMs), such as the tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-1ß (IL-10), nitric oxide (NO), and cyclooxygenase-2 (COX-2), among others. Various studies have shown the role of neuroinflammatory markers in the occurrence, diagnosis, and treatment of neurodegenerative diseases. These markers also trigger the formation of various other factors responsible for causing several neuronal diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), ischemia, and several others. This comprehensive review aims to reveal the mechanism of neuroinflammatory markers (NMs), which could cause different neurodegenerative disorders. Important NMs may represent pathophysiologic processes leading to the generation of neurodegenerative diseases. In addition, various molecular alterations related to neurodegenerative diseases are discussed. Identifying these NMs may assist in the early diagnosis and detection of therapeutic targets for treating various neurodegenerative diseases.
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Doenças Neurodegenerativas , Biomarcadores , Humanos , Inflamação/patologia , Interleucina-1beta , Microglia/patologia , Doenças Neurodegenerativas/patologiaRESUMO
Shigellosis is characterized as diarrheal disease that causes a high mortality rate especially in children, elderly and immunocompromised patients. More recently, the World Health Organization advised safe vaccine designing against shigellosis due to the emergence of Shigella dysenteriae resistant strains. Therefore, the aim of this study is to identify novel drug targets as well as the design of the potential vaccine candidates and chimeric vaccine models against Shigella dysenteriae. A computational based Reverse Vaccinology along with subtractive genomics analysis is one of the robust approaches used for the prioritization of drug targets and vaccine candidates through direct screening of genome sequence assemblies. Herein, a successfully designed peptide-based novel highly antigenic chimeric vaccine candidate against Shigella dysenteriae sd197 strain is proposed. The study resulted in six epitopes from outer membrane WP_000188255.1 (Fe (3+) dicitrate transport protein FecA) that ultimately leads to the construction of twelve vaccine models. Moreover, V9 construct was found to be highly immunogenic, non-toxic, non-allergenic, highly antigenic, and most stable in terms of molecular docking and simulation studies against six HLAs and TLRS/MD complex. So far, this protein and multiepitope have never been characterized as vaccine targets against Shigella dysenteriae. The current study proposed that V9 could be a significant vaccine candidate against shigellosis and to ascertain that further experiments may be applied by the scientific community focused on shigellosis.
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Antibacterianos/farmacologia , Vacinas Bacterianas/farmacologia , Desenho de Fármacos , Disenteria Bacilar/prevenção & controle , Shigella dysenteriae/efeitos dos fármacos , Desenvolvimento de Vacinas/métodos , Vacinologia/métodos , Animais , Antígenos de Bactérias/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/microbiologia , Proteínas de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Desenho Assistido por Computador , Disenteria Bacilar/imunologia , Disenteria Bacilar/metabolismo , Disenteria Bacilar/microbiologia , Epitopos , Interações Hospedeiro-Patógeno , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Farmacologia em Rede , Shigella dysenteriae/imunologia , Shigella dysenteriae/patogenicidade , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/microbiologiaRESUMO
Saffron (Crocus sativus L., family Iridaceae) is used traditionally for medicinal purpose in Chinese, Ayurvedic, Persian and Unani medicines. The bioactive constituents such as apocarotenoids, monoterpenoids, flavonoids, phenolic acids and phytosterols are widely investigated in experimental and clinical studies for a wide range of therapeutic effects, especially on the nervous system. Some of the active constituents of saffron have high bioavailability and bioaccessibility and ability to pass the blood-brain barrier. Multiple preclinical and clinical studies have supported neuroprotective, anxiolytic, antidepressant, learning and memory-enhancing effect of saffron and its bioactive constituents (safranal, crocin, and picrocrocin). Thus, this plant and its active compounds could be a beneficial medicinal food ingredient in the formation of drugs targeting nervous system disorders. This review focuses on phytochemistry, bioaccessibility, bioavailability, and bioactivity of phytochemicals in saffron. Furthermore, the therapeutic effect of saffron against different nervous system disorders has also been discussed in detail.
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Crocus , Antidepressivos , Crocus/química , Flavonoides , Compostos Fitoquímicos/química , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
The current review discuss the chemistry, nutritional composition, toxicity, and biological functions of garlic and its bioactive compounds against various types of cancers via different anticancer mechanisms. Several scientific documents were found in reliable literature and searched in databases viz Science Direct, PubMed, Web of Science, Scopus, and Research Gate were carried out using keywords such as "garlic", "garlic bioactive compounds", "anticancer mechanisms of garlic", "nutritional composition of garlic", and others. Garlic contains several phytoconstituents with activities against cancer, and compounds such as diallyl trisulfide (DATS), allicin, and diallyl disulfide (DADS), diallyl sulfide (DAS), and allyl mercaptan (AM). The influence of numerous garlic- derived products, phytochemicals, and nanoformulations on the liver, oral, prostate, breast, gastric, colorectal, skin, and pancreatic cancers has been studied. Based on our search, the bioactive molecules in garlic were found to inhibit the various phases of cancer. Moreover, the compounds in this plant also abrogate the peroxidation of lipids, activity of nitric oxide synthase, epidermal growth factor (EGF) receptor, nuclear factor-kappa B (NF-κB), protein kinase C, and regulate cell cycle and survival signaling cascades. Hence, garlic and its bioactive molecules exhibit the aforementioned mechanistic actions, and thus, they could be used to inhibit the induction, development, and progression of cancer. The review describes the nutritional composition of garlic, its bioactive molecules, and nanoformulations against various types of cancers, as well as the potential for developing these agents as antitumor drugs.
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Antineoplásicos , Produtos Biológicos , Alho , Antineoplásicos/farmacologia , Antioxidantes , Dissulfetos/farmacologia , Alho/química , Sulfetos/químicaRESUMO
Remdesivir and hydroxychloroquine derivatives form two important classes of heterocyclic compounds. They are known for their anti-malarial biological activity. This research aims to analyze the physicochemical properties of remdesivir and hydroxychloroquine compounds by the computational approach. DFT, docking, and POM analyses also identify antiviral pharmacophore sites of both compounds. The antiviral activity of hydroxychloroquine compound's in the presence of zinc sulfate and azithromycin is evaluated through its capacity to coordinate transition metals (M = Cu, Ni, Zn, Co, Ru, Pt). The obtained bioinformatic results showed the potent antiviral/antibacterial activity of the prepared mixture (Hydroxychloroquine/Azithromycin/Zinc sulfate) for all the opportunistic Gram-positive, Gram-negative in the presence of coronavirus compared with the complexes Polypyridine-Ruthenium-di-aquo. The postulated zinc(II) complex of hydroxychloroquine derivatives are indeed an effective antibacterial and antiviral agent against coronavirus and should be extended to other pathogens. The combination of a pharmacophore site with a redox [Metal(OH2)2] moiety is of crucial role to fight against viruses and bacteria strains. [Formula: see text]Communicated by Ramaswamy H. Sarma.
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COVID-19 , Hidroxicloroquina , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Hidroxicloroquina/química , Sulfato de Zinco , Antivirais/farmacologia , Antivirais/química , Azitromicina/química , Simulação de Acoplamento MolecularRESUMO
Berberine (BBR), a potential bioactive agent, has remarkable health benefits. A substantial amount of research has been conducted to date to establish the anticancer potential of BBR. The present review consolidates salient information concerning the promising anticancer activity of this compound. The therapeutic efficacy of BBR has been reported in several studies regarding colon, breast, pancreatic, liver, oral, bone, cutaneous, prostate, intestine, and thyroid cancers. BBR prevents cancer cell proliferation by inducing apoptosis and controlling the cell cycle as well as autophagy. BBR also hinders tumor cell invasion and metastasis by down-regulating metastasis-related proteins. Moreover, BBR is also beneficial in the early stages of cancer development by lowering epithelial-mesenchymal transition protein expression. Despite its significance as a potentially promising drug candidate, there are currently no pure berberine preparations approved to treat specific ailments. Hence, this review highlights our current comprehensive knowledge of sources, extraction methods, pharmacokinetic, and pharmacodynamic profiles of berberine, as well as the proposed mechanisms of action associated with its anticancer potential. The information presented here will help provide a baseline for researchers, scientists, and drug developers regarding the use of berberine as a promising candidate in treating different types of cancers.
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Antineoplásicos/uso terapêutico , Berberina/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Berberina/farmacologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , HumanosRESUMO
It has become evident over the past several years that the intestinal microbial ecosystem plays a critical role in the development and prevention of cardiovascular diseases (CVDs) and other metabolic disorders, such as hypertension, obesity, diabetes mellitus, and metabolic syndrome. The intestinal microbiota ecosystem functions as a major virtual endocrine organ that interacts and responds to molecules' signals within the host. Several meta-organismal pathways are involved in the gut-host interaction, including trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFA). Host phenotype and cardiovascular diseases (CVDs) varying from hypertension, insulin resistance, and obesity to more specific inflammatory processes, such as atherosclerosis and hypercoagulability, have shown to be affected by the gut-host interaction. Additionally, several studies that involved animals and humans demonstrated a striking connection between the development of new CVDs and an imbalance in the gut microbiota composition along with the presence of their derived metabolites. Through this review article, we aim to evaluate the role of the normal gut microbiota ecosystem, its association with CVDs, effects of the therapies used to control and manage CVDs in the gut microbiota environment and explore potential therapeutic interventions to amplify disease outcomes in patients with CVDs.
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Tobacco is grown in large quantities worldwide as a widely distributed commercial crop. From the harvest of the field to the process into the final product, a series of procedures generate enormous amount of waste materials that are rarely recycled. In recent years, numerous potential bioactive compounds have been isolated from tobacco, and the molecular regulatory mechanisms related to the performance of some functionalities have been identified. This review describes the source of tobacco waste and expounds a large amount of biomass during the tobacco processing, and the necessity of exploring the reuse of tobacco waste. In addition, the review summarizes the bioactive compounds from tobacco that have been discovered so far, and links them to various functions from tobacco extracts, including anti-inflammatory, antitumor, antibacterial, and antioxidant, thus proving the potential value from tobacco waste reuse. In this regard, nornicotine in tobacco is the culprit of many health issues, while the polyphenols and polysaccharides often contribute to the health benefits of tobacco extract. In addition, it is hard to ignore that realization of these functions of tobacco extracts require the involvement of intestinal flora metabolism, which should be considered in the development of new product dosage forms.