RESUMO
Pyrogallol, a botanical hydrolysable tannin, has diverse medical and industrial applications. Its impact on aquatic ecosystems and fish health has been previously studied, revealing histopathological, immunological, biochemical, and haematological alterations in African catfish (Clarias gariepinus). In this study, the neurotoxic potential of pyrogallol was assessed through a 15-day exposure of catfish to concentrations of 1, 5, or 10â¯mg/L. Enzyme activities such as acetylcholinesterase (AchE), monoamine oxidase (MAO), aldehyde oxidase (AO), and nitric oxide (NO) were measured in serum and brain, along with histopathological examinations in the brain and heart. Pyrogallol exposure led to decreased AchE activity in the brain and serum, increased serum MAO activity, elevated AO in both brain and serum, and suppressed NO levels. Morphological abnormalities and dose-dependent pathological alterations were observed in the brain and heart, including neuropile deformities, shrunken Purkinje cells, cardiomyocyte degeneration, and increased collagen fibers. This suggests that pyrogallol induces adverse effects in fish.
Assuntos
Encéfalo , Peixes-Gato , Óxido Nítrico , Pirogalol , Poluentes Químicos da Água , Animais , Óxido Nítrico/metabolismo , Óxido Nítrico/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Pirogalol/toxicidade , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Acetilcolinesterase/sangue , Coração/efeitos dos fármacos , Miocárdio/patologia , Miocárdio/metabolismo , Monoaminoxidase/metabolismo , CardiotoxicidadeRESUMO
Cyanobacteria blooms (CBs) caused by eutrophication pose a global concern, especially Microcystis aeruginosa (M. aeruginosa), which could release harmful microcystins (MCs). The impact of microplastics (MPs) on allelopathy in freshwater environments is not well understood. This study examined the joint effect of adding polystyrene (PS-MPs) as representative MPs and two concentrations (2 and 8 mg/L) of pyrogallol (PYR) on the allelopathy of M. aeruginosa. The results showed that the addition of PS-MPs intensified the inhibitory effect of 8 mg/L PYR on the growth and photosynthesis of M. aeruginosa. After a 7-day incubation period, the cell density decreased to 69.7 %, and the chl-a content decreased to 48 % compared to the condition without PS-MPs (p < 0.05). Although the growth and photosynthesis of toxic Microcystis decreased with the addition of PS-MPs, the addition of PS-MPs significantly resulted in a 3.49-fold increase in intracellular MCs and a 1.10-fold increase in extracellular MCs (p < 0.05). Additionally, the emission rates of greenhouse gases (GHGs) (carbon dioxide, nitrous oxide and methane) increased by 2.66, 2.23 and 2.17-fold, respectively (p < 0.05). In addition, transcriptomic analysis showed that the addition of PS-MPs led to the dysregulation of gene expression related to DNA synthesis, membrane function, enzyme activity, stimulus detection, MCs release and GHGs emissions in M. aeruginosa. PYR and PS-MPs triggered ROS-induced membrane damage and disrupted photosynthesis in algae, leading to increased MCs and GHG emissions. PS-MPs accumulation exacerbated this issue by impeding light absorption and membrane function, further heightening the release of MCs and GHGs emissions. Therefore, PS-MPs exhibited a synergistic effect with PYR in inhibiting the growth and photosynthesis of M. aeruginosa, resulting in additional risks such as MCs release and GHGs emissions. These results provide valuable insights for the ecological risk assessment and control of algae bloom in freshwater ecosystems.
Assuntos
Gases de Efeito Estufa , Microcistinas , Microcystis , Microplásticos , Pirogalol , Microcystis/fisiologia , Microcystis/efeitos dos fármacos , Microcistinas/toxicidade , Microplásticos/toxicidade , Alelopatia , Poluentes Químicos da Água/toxicidade , Fotossíntese/efeitos dos fármacosRESUMO
Previously, we have shown that pyrogallol alleviated nasal symptoms and suppressed IL-9 gene up-regulation in allergy model rats by inhibiting calcineurin/NFAT signaling. As pyrogallol has antioxidative activity, it may be responsible for inhibiting calcineurin/NFAT signaling-mediated IL-9 gene expression. However, the relationship between antioxidative activity and suppression of IL-9 gene expression has not been elucidated yet. Here, we conducted the structure-activity relationship studies of pyrogallol and its structurally related compounds to understand the mechanism of IL-9 gene suppression by pyrogallol. 2, 2-Diphenyl-1-picrylhydrazyl radical scavenging assay showed that the antioxidative activity of catechol, resorcinol, phloroglucinol, and gallic acid is 60.1%, 10.4%, 18.8%, and 113.5% of pyrogallol, respectively. Catechol, resorcinol, and phloroglucinol did not suppress NFAT dephosphorylation. Gallic acid suppressed dephosphorylation of NFAT. Gallic acid also suppressed ionomycin-induced up-regulation of IL-9 gene expression with the IC50 value of 82.6 µM. However, catechol, resorcinol and phloroglucinol showed no suppressive activity. In addition, using gallic acid-immobilized beads, we isolated and identified Poly(U)-binding-splicing factor 60 (PUF60) as a pyrogallol binding protein. These results suggest that the antioxidative activity of pyrogallol is not likely to be the mechanism of IL-9 gene suppression. Data also suggest that PUF60 is one of its target molecules responsible for the suppression of calcineurin/NFAT signaling by pyrogallol.
Assuntos
Antioxidantes , Calcineurina , Fatores de Transcrição NFATC , Pirogalol , Transdução de Sinais , Pirogalol/farmacologia , Calcineurina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Relação Estrutura-Atividade , Antioxidantes/farmacologia , Humanos , Ácido Gálico/farmacologia , Expressão Gênica/efeitos dos fármacos , Animais , Fosforilação/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , RatosRESUMO
The 1967 attempt of structural analysis of the solid-state complex of caffeine and pyrogallol was a pioneering structural investigation in the supramolecular chemistry of caffeine, of what today would easily be considered an archetype of a model pharmaceutical cocrystal. Re-investigating this historically important system demonstrates that this long overlooked complex is most likely a tetrahydrate with a different structure and composition than initially proposed, and provides the crystal structure of the anhydrous cocrystal.
Assuntos
Cafeína , Pirogalol , Cafeína/química , Pirogalol/química , Pirogalol/análogos & derivados , Estrutura Molecular , Cristalização , Modelos Moleculares , Cristalografia por Raios XRESUMO
This study unveils a novel role of pyrogallol (PG), a recognized superoxide generator, in inducing beta-amyloid (Aß) secretion in an Alzheimer's disease (AD) cellular model. Contrary to expectations, the analysis of dihydroethidium fluorescence and UV-VIS spectrum scanning reveals that Aß secretion arises from PG reaction intermediates rather than superoxide or other by-products. Investigation into Aß secretion mechanisms identifies dynasore-dependent endocytosis and BFA-dependent exocytosis as independent pathways, regulated by tiron, tempol, and superoxide dismutase. Cell-type specificity is observed, with 293sw cells showing both pathways, while H4sw cells and primary astrocytes from an AD animal model exclusively exhibit the Aß exocytosis pathway. This exploration contributes to understanding PG's chemical reactions and provides insights into the interplay between environmental factors, free radicals, and AD, linking occupational PG exposure to AD risk as reported in the literature.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Pirogalol , Superóxidos , Peptídeos beta-Amiloides/metabolismo , Humanos , Pirogalol/farmacologia , Pirogalol/análogos & derivados , Superóxidos/metabolismo , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Astrócitos/metabolismo , Exocitose , Endocitose , Superóxido Dismutase/metabolismo , Óxidos N-Cíclicos/farmacologiaRESUMO
Endocrine disruptors are synthetic or natural chemicals that can agonize/antagonize hormone receptors or can interfere with the production and secretion of hormones, leading to altered tissue histology and physiology. Pyrogallol is a contaminant widely distributed in aquatic environments that presents health risks to both humans and animals. However, the potential for endocrine disruption by pyrogallol, particularly in fish, are lacking. The purpose of this study was to shed light on how pyrogallol may affect hormone signalling, histopathology, and reproductive outcomes in African catfish Clarias gariepinus. To investigate this, African catfish were exposed to one sublethal concentration of pyrogallol at either 0, 1, 5 or 10 mg/L for 15 days. We then assessed the effects of pyrogallol on the thyroid gland as well as the reproductive system by measuring sex hormone, seminal quality, gonadal histopathology, and histochemistry. Thyroid stimulating hormone and thyroxine showed notable decreases in catfish, and triiodothyronine was decreased with 10 mg/L pyrogallol. Unlike luteinizing hormone, follicle-stimulating hormone was significantly reduced in fish following exposure to pyrogallol relative to controls. Testosterone was also decreased in fish following pyrogallol exposure, whereas 17ß-estradiol increased in catfish exposed to pyrogallol. Additionally, in response to pyrogallol toxicity, sperm quality indices, including count, spermatocrit, motility, and sperm viability were adversely affected in a concentration-dependent manner. Pyrogallol exposure also induced several changes in the gonad following exposure to 1, 5, or 10 mg/L. Deformed tubular structures, vacuolation, thickening of the basement membrane, hypertrophy of the seminiferous tubules, intense melanomacrophage localization, spermatozoa loss, and necrosis were all observed in the testes. In the ovary, atretic follicles, deteriorated mature oocytes, degenerated yolk globules, and an increase in perinucleolar oocytes were observed in catfish exposed to pyrogallol. These findings suggest that pyrogallol may act as endocrine disrupting substance in aquatic environments. Further research on the mechanisms by which pyrogallol impairs endocrine systems, particularly in fish, is recommended.
Assuntos
Peixes-Gato , Disruptores Endócrinos , Pirogalol , Reprodução , Poluentes Químicos da Água , Animais , Peixes-Gato/fisiologia , Disruptores Endócrinos/toxicidade , Poluentes Químicos da Água/toxicidade , Reprodução/efeitos dos fármacos , Masculino , Pirogalol/toxicidade , Pirogalol/análogos & derivados , Feminino , Glândula Tireoide/efeitos dos fármacosRESUMO
Lignin, a renewable natural antioxidant and bacteriostat, holds promise as a versatile, cost-effective feed additive. However, traditional industrial lignin faces limitations, including low reactivity, poor uniformity, and unstable properties, necessitating chemical modification. Complex modification methods pose economic and toxicity challenges, so this study adopted a relatively simple alkali-catalyzed phenolization approach, using phenol, catechol, and pyrogallol to modify kraft lignin, and characterized the resulting products using various techniques. Subsequently, their antioxidant, antibacterial, adsorption properties for heavy metal ions and mycotoxins, growth-promoting properties, and antiviral abilities were assessed. The phenolation process led to lignin depolymerization and a notable increase in phenolic hydroxyl content, particularly in pyrogallol-phenolated lignin (Py-L), rising from 3.08 to 4.68 mmol/g. These modified lignins exhibited enhanced antioxidant activity, with over 99 % inhibition against E. coli and S. aureus, and remarkable adsorption capacities for heavy metal ions and mycotoxins. Importantly, Py-L improved the growth performance of mice and reduced influenza mortality. Furthermore, density functional theory calculations elucidated the mechanism behind the enhanced antioxidant properties. This study presents a promising avenue for developing versatile feed additives to address challenges related to animal feed antioxidant supplementation, bacterial control, and growth promotion.
Assuntos
Ração Animal , Antioxidantes , Lignina , Lignina/química , Antioxidantes/química , Antioxidantes/farmacologia , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Fenóis/química , Fenóis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Adsorção , Pirogalol/química , Pirogalol/farmacologia , Metais Pesados/química , Micotoxinas/química , Micotoxinas/farmacologiaRESUMO
Polyphenol hydrogels have garnered widespread attention due to their excellent adhesion, antioxidant, and antibacterial properties. Gallic acid (GA) is a typical derivative of pyrogallol that is used as a hydrogel crosslinker or bioactive additive and can be used to make multifunctional hydrogels with properties superior to those of widely studied catechol hydrogels. Furthermore, compared to polymeric tannic acid, gallic acid is more suitable for chemical modification, thus broadening its range of applications. This review focuses on multifunctional hydrogels containing GA, aiming to inspire researchers in future biomaterial design. We first revealed the interaction mechanisms between GA molecules and between GA and polymers, analyzed the characteristics GA imparts to hydrogels and compared GA hydrogels with hydrogels containing catechol. Subsequently, in this paper, various methods of integrating GA into hydrogels and the applications of GA in biomedicine are discussed, finally assessing the current limitations and future development potential of GA. In summary, GA, a natural small molecule polyphenol with excellent functionality and diverse interaction modes, has great potential in the field of biomedical hydrogels.
Assuntos
Ácido Gálico , Pirogalol , Ácido Gálico/farmacologia , Ácido Gálico/química , Pirogalol/farmacologia , Hidrogéis/química , Polifenóis , CatecóisRESUMO
This study was designed to investigate the effect of polyphenolic structure on the interaction strength and process between polyphenols (gallic acid (GA), epigallocatechin gallate (EGCG) and tannic acid (TA)) and amylose (AM). The results of Fourier transform infrared spectroscopy, isothermal titration calorimetry, X-ray photoelectron spectroscopy and molecular dynamic simulation (MD) suggested that the interactions between the three polyphenols and AM were noncovalent, spontaneous, low-energy and driven by enthalpy, which would be enhanced with increasing amounts of pyrogallol groups in the polyphenols. The results of turbidity, particle size and appearance of the complex solution showed that the interaction process between polyphenols and AM could be divided into three steps and would be advanced by increasing the number of pyrogallol groups in the polyphenols. At the same time, MD was intuitively employed to exhibit the interaction process between amylose and polyphenols, and it revealed that the interaction induced the aggregation of amylose and that the agglomeration degree of amylose increased with increasing number of pyrogallol groups at polyphenols. Last, the SEM and TGA results showed that TA/AM complexes had the tightest structure and the highest thermal stability (TA/AMËEGCG/AMËGA/AM), which could be attributed to TA having five pyrogallol groups.
Assuntos
Amilose , Pirogalol , Pirogalol/química , Polifenóis/química , Ácido Gálico/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Perillae Folium, the leaves and twigs of Perilla frutescens (L.) Britton, has been included in many traditional Chinese medicine herbal formulas to treat depression. However, the precise antidepressant mechanism of the essential oil from Perillae Folium (PFEO) has not been fully investigated. AIM OF THE STUDY: To assess the effects and potential mechanisms of PFEO on depression using animal models and network pharmacology analysis. MATERIALS AND METHODS: PFEO was intranasally administered to a mouse model of social defeat stress (SDS). The antidepressant effects of PFEO on SDS-induced mice were evaluated using behavioral tests. Enzyme-linked immunosorbent assay (ELISA) and western blot were performed to measure the levels of depression-related biomarkers in the hippocampus and serum of the mice. The chemical compounds of PFEO were determined using gas chromatography-mass spectrometry (GC-MS). Network pharmacology and molecular docking analyses were conducted to investigate the potential bioactive components of PFEO and the mechanisms underlying the antidepressant effects. To validate the mechanisms of the bioactive compounds, in vitro models using PC12 and BV2 cells were established and the blood-brain barrier (BBB) permeability was evaluated. RESULTS: The intranasal administration of PFEO suppressed SDS-induced depression in mice by increasing the time spent in the social zone and the social interactions in the social interaction test and by decreasing the immobility time in the tail suspension and forced swimming tests. Moreover, the PFEO treatment reduced the SDS-induced anxiety-like behavior, as inferred from the increased activity in the central zone observed in the open field test and in the open arms observed in the elevated plus maze test. PFEO administration recovered the SDS-induced decrease in the levels of 5-HT, NE, gamma-aminobutyric acid (GABA), and p-ERK in the hippocampus of mice. Furthermore, the increased serum corticosterone level was also attenuated by the PFEO treatment. A total of 21 volatile compounds were detected in PFEO using GC-MS, among which elemicin (15.52%), apiol (15.16%), and perillaldehyde (12.79%) were the most abundant ones. The PFEO compounds targeted 32 depression-associated genes, which were mainly related to neural cells and neurotransmission pathways. Molecular docking indicated good binding affinities between the bioactive components of PFEO (apiol, ß-caryophyllene, elemicin, and myristicin) and the key targets, including ACHE, IL1B, IL6, MAOB, SLC6A2, SLC6A3, SLC6A4, and tumor necrosis factor. Among the four compounds, ß-caryophyllene, elemicin, and myristicin were more effective in reducing neurotoxicity and neuroinflammation. Elemicin showed the highest BBB permeability rate. CONCLUSIONS: This study shows the antidepressant activities of PFEO in an SDS-induced mouse model and suggests its potential mechanisms of action: regulation of the corticosterone levels, hippocampal neurotransmitters, and ERK signaling. Apiol, ß-caryophyllene, elemicin, and myristicin may be the main contributors to the observed effects induced by PFEO. Further studies are needed to fully elucidate the underlying mechanisms and the main PFEO bioactive components.
Assuntos
Derivados de Alilbenzenos , Depressão , Dioxolanos , Óleos Voláteis , Sesquiterpenos Policíclicos , Pirogalol/análogos & derivados , Animais , Camundongos , Depressão/tratamento farmacológico , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Corticosterona , Administração Intranasal , Simulação de Acoplamento Molecular , Derrota Social , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal , Hipocampo , Modelos Animais de DoençasRESUMO
Antibacterial hydrogels have emerged as a promising approach for wound healing, owing to their ability to integrate antibacterial agents into the hydrogel matrix. Benefiting from its remarkable antibacterial and wound-healing attributes, pyrogallol has been introduced into chitosan-gelatin for the inaugural development of an innovative antibacterial polymeric hydrogel tailored for applications in wound healing. Hence, we observed the effectiveness of pyrogallol in inhibiting the growth of A. baumannii, disrupting mature biofilms, and showcasing robust antioxidant activity both in vitro and in vivo. In addition, pyrogallol promoted the migration of human epidermal keratinocytes and exhibited wound healing activity in zebrafish. These findings suggest that pyrogallol holds promise as a therapeutic agent for wound healing. Interestingly, the pyrogallol-loaded chitosan-gelatin (Pyro-CG) hydrogel exhibited enhanced mechanical strength, stability, controlled drug release, biodegradability, antibacterial activity, and biocompatibility. In vivo results established that Pyro-CG hydrogel promotes wound closure and re-epithelialization in A. baumannii-induced wounds in molly fish. Therefore, the prepared Pyro-CG polymeric hydrogel stands poised as a potent and promising agent for wound healing with antibacterial properties. This holds considerable promise for the development of effective therapeutic interventions to address the increasing menace of A. baumannii-induced wound infections.
Assuntos
Acinetobacter baumannii , Quitosana , Infecção dos Ferimentos , Animais , Humanos , Hidrogéis/farmacologia , Pirogalol , Gelatina , Peixe-Zebra , Antibacterianos/farmacologiaRESUMO
In more than 50 to 90% of type 2 diabetic patients, under the influence of various factors, the production of islet amyloid polypeptide or amylin in pancreatic beta cells increases. Spontaneous accumulation of amylin peptide in the form of insoluble amyloid fibrils and soluble oligomers is one of the main causes of beta cell death in diabetic patients. The objective of the present study was to evaluate the effect of pyrogallol, as a phenolic compound, on inhibiting the formation of amylin protein amyloid fibrils. In this study, different techniques such as the thioflavin T (ThT) and 1-Anilino-8-naphthalene sulfonate (ANS) fluorescence intensity and the circular dichroism (CD) spectrum, will be used to investigate the effects of this compound on inhibiting the formation of amyloid fibrils. To investigate the interaction sites of pyrogallol with amylin, docking studies were performed. Our results that pyrogallol in a dose-dependent manner (0.5:1, 1:1, and 5:1, Pyr to Amylin) inhibits the amylin amyloid fibrils formation. Docking analysis revealed that pyrogallol forms hydrogen bonds with valine 17 and asparagine 21. In addition, this compound forms 2 more hydrogen bonds with asparagine 22. This compound also forms hydrophobic bonds with histidine 18. Considering this data and the direct relationship between oxidative stress and the formation of amylin amyloid accumulations in diabetes, the use of compounds with both antioxidant and anti-amyloid properties can be considered an important therapeutic strategy for type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Amiloide/química , Amiloide/metabolismo , Pirogalol , AsparaginaRESUMO
Plants in the maple genus, Acer, and pistachio genus, Pistacia, have been reported to cause acute hemolysis in horses. The cause of hemolysis seems to be metabolism of gallic acids to the potent oxidant pyrogallol by enteric bacteria of the horse. Diagnosis is often tentative and circumstantial. Treatment is symptomatic and supportive and can include detoxification, fluid and electrolyte therapy, supplemental oxygen, and pain control. Corticosteroid and antioxidant therapies do not improve prognosis. Prognosis is guarded to poor but horses that survive 6 days postexposure are expected to recover.
Assuntos
Doenças dos Cavalos , Intoxicação por Plantas , Cavalos , Animais , Pirogalol , Hemólise , Intoxicação por Plantas/complicações , Intoxicação por Plantas/veterinária , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/terapia , Ácido GálicoRESUMO
Flavonoids are known to covalently modify amyloidogenic peptides by amination reactions. The underlying coupling process between polyphenols and N-nucleophiles is assessed by several inâ vitro and in silico approaches. The coupling reaction involves a sequence of oxidative dearomatization, amination, and reductive amination (ODARA) reaction steps. The C6-regioselectivity of the product is confirmed by crystallographic analysis. Under aqueous conditions, the reaction of baicalein with lysine derivatives yields C-N coupling as well as hydrolysis products of transient imine intermediates. The observed C-N coupling reactions work best for flavonoids combining a pyrogallol substructure with an electron-withdrawing group attached to the C4a-position. Thermodynamic properties such as bond dissociation energies also highlight the key role of pyrogallol units for the antioxidant ability. Combining the computed electronic properties and inâ vitro antioxidant assays suggests that the studied pyrogallol-containing flavonoids act by various radical-scavenging mechanisms working in synergy. Multivariate analysis indicates that a small number of descriptors for transient intermediates of the ODARA process generates a model with excellent performance (r=0.93) for the prediction of cross-coupling yields. The same model has been employed to predict novel antioxidant flavonoid-based molecules as potential covalent inhibitors, opening a new avenue to the design of therapeutically relevant anti-amyloid compounds.
Assuntos
Antioxidantes , Polifenóis , Antioxidantes/química , Pirogalol , Aminação , Flavonoides/química , OxirreduçãoRESUMO
This current study reports, for the first time, on the potent cytotoxicity of (Z)-3-hexenyl-ß-D-glucopyranoside, as well as its cellular and molecular apoptotic mechanisms against Panc1 cancer cells. The cytotoxicity of three compounds, namely (Z)-3-hexenyl-ß-D-glucopyranoside (1), gallic acid (2), and pyrogallol (3), which were isolated from C. rotang leaf, was investigated against certain cancer and normal cells using the MTT assay. The cellular apoptotic activity and Panc1 cell cycle impact of compound (1) were examined through flow cytometry analysis and Annexin V-FITC cellular apoptotic assays. Additionally, RT-PCR was employed to evaluate the effect of compound (1) on the Panc1 apoptotic genes Casp3 and Bax, as well as the antiapoptotic gene Bcl-2. (Z)-3-hexenyl-ß-D-glucopyranoside demonstrated the highest cytotoxic activity against Panc1 cancer cells, with an IC50 value of 7.6 µM. In comparison, gallic acid exhibited an IC50 value of 21.8 µM, and pyrogallol showed an IC50 value of 198.2 µM. However, (Z)-3-hexenyl-ß-D-glucopyranoside displayed minimal or no significant cytotoxic activity against HepG2 and MCF7 cancer cells as well as WI-38 normal cells, with IC50 values of 45.8 µM, 108.7 µM, and 194. µM, respectively. (Z)-3-hexenyl-ß-D-glucopyranoside (10 µM) was demonstrated to induce cellular apoptosis and cell growth arrest at the S phase of the cell cycle in Panc1 cells. These findings were supported by RT-PCR analysis, which revealed the upregulation of apoptotic genes (Casp3 and Bax) and the downregulation of the antiapoptotic gene Bcl-2. This study emphasizes the significant cellular potency of (Z)-3-hexenyl-ß-D-glucopyranoside in specifically inducing cytotoxicity in Panc1 cells.
Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Humanos , Caspase 3 , Proteína X Associada a bcl-2 , Pirogalol/farmacologia , Antineoplásicos/farmacologia , Células MCF-7 , Apoptose , Ácido Gálico/farmacologia , Linhagem Celular TumoralRESUMO
Pyrogallol is a naturally occurring polyphenol derived from natural plants, such as Acer rubrum and Eucalyptus sp. The current study was designed to evaluated pyrogallol-mediated toxicity at sublethal levels (1, 5, and 10 mg/L), derived from 96 h-LC50 values previously determined for African catfish (Clarias gariepinus). Immunotoxicological indices, histological, histochemical, and ultrastructural alterations in C. gariepinus were evaluated following a 15-day pyrogallol exposure. Pyrogallol decreased immune parameters [lysozyme activity (LYZ), immunoglobulin M (IgM), and phagocytic activity] and increased pro-inflammatory cytokines, interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) in the serum of C. gariepinus. In addition, histopathology analysis demonstrated that exposure to pyrogallol induced injury in the liver and spleen of fish. Cellular changes in the liver include hepatocyte hydropic degeneration, melanomacrophage, vacuolated hepatocytes, congested blood, severe structural deformation, and hemorrhage. In the spleen, ellipsoid structures, melanomacrophage centers, and infiltration of inflammatory cells were evident. Together, a high frequency of histopathological lesions was scored in both the liver and spleen of C. gariepinus, which showed a dose-dependent relationship between pyrogallol exposure and histopathological indices. Our data suggest that dysfunction in the immune system may be mediated by pyrogallol-induced changes in cytokines.
Assuntos
Peixes-Gato , Poluentes Químicos da Água , Animais , Pirogalol/toxicidade , Fígado , Citocinas , Poluentes Químicos da Água/análiseRESUMO
Pyrogallol promotes free radicals leading to oxidative stress and toxicity. There are however a lack of studies on oxidative stress and the antioxidant system of fish following exposure to pyrogallol. This study measured oxidative stress markers, antioxidant responses, and histological changes in catfish exposed to pyrogallol. Fish were divided into one of four experimental groups: control only, or 1, 5 or 10 mg/L pyrogallol. After 15 days, glutathione-S-transferase in the serum was decreased in fish exposed to either 5 or 10 mg/L pyrogallol relative to controls while superoxide dismutase and total antioxidant capacity were decreased significantly in fish exposed to 1, 5, or 10 mg/L pyrogallol. Conversely, catalase was increased in serum of fish exposed to 1, 5, or 10 mg/L pyrogallol compared to controls. The liver of fish treated with 1, 5, or 10 mg/L pyrogallol had significantly higher levels of oxidative stress markers (malondialdehyde, lipid peroxidation, hydroperoxide content, oxidised protein content, and DNA fragmentation %) that varied with concentration. Catfish exposed to either 1, 5, or 10 mg/L pyrogallol presented with notable histological alterations in the intestine, kidney, and muscles with prominent fibrosis, as intense deposition of collagen fibre was observed by Masson's trichrome staining. Overall, endpoints related to oxidative stress and antioxidant defence enzymes in fish may be early biomarkers of pyrogallol exposure and contamination in aquatic ecosystems. Additional studies should characterize oxidative stress indicators for their utility as biomarkers of effect.
Assuntos
Peixes-Gato , Poluentes Químicos da Água , Animais , Antioxidantes/metabolismo , Pirogalol/toxicidade , Pirogalol/metabolismo , Ecossistema , Estresse Oxidativo , Peixes-Gato/metabolismo , Biomarcadores/metabolismo , Peroxidação de Lipídeos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismoRESUMO
Pyrogallol (1,2,3-trihydroxybenzene), a polyphenolic natural compound, has attracted considerable attention with regard to its potential anticancer activity. However, further study is needed to elucidate the underlying mechanism related to the antiNSCLC activity of pyrogallol and provide a comprehensive theoretical basis for better clinical utilization of pyrogallol. Our current study aims to investigate the effects and potential underlying mechanisms of pyrogallol on the inhibition of NSCLC growth. Our results showed that pyrogallol treatment induced cell cycle arrest at the G2/M phase and apoptosis in two different NSCLC cell lines. Mechanistically, we found that the induction of cell cycle arrest in NSCLC cells at the G2/M phase by pyrogallol was due to the upregulation of p21 in a p53-dependent manner. And blockade of p53 and p21 effectively abolished the cell cycle arrest at the G2/M phase. Meanwhile, p53 inhibition has been found to abrogate the pyrogallol-induced apoptosis of the two NSCLC cells. Moreover, we revealed that the inhibitory effects of pyrogallol on ß-catenin signaling resulted from autophagy initiation depending on p53 activation, accompanied by an increase in p62/SQSTM1 expression, thus p62 subsequently interacting with ubiquitinated ß-catenin and facilitating autophagic destruction of ß-catenin. Furthermore, in vivo experiments demonstrated that pyrogallol exerted growth inhibition on NSCLC with low toxicity through the same molecular mechanism as observed in vitro. Our findings could contribute to the understanding of the mechanism by which pyrogallol negatively regulates NSCLC growth, which could be effective in treating NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Pirogalol/farmacologia , Pirogalol/uso terapêutico , Regulação para Cima , Proteína Supressora de Tumor p53/metabolismo , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , beta Catenina/metabolismo , Linhagem Celular Tumoral , Apoptose , Proliferação de CélulasRESUMO
AIMS: To examine the effect of the phenolic compound pyrogallol on staphylococcal biofilm formation. METHODS AND RESULTS: In crystal violet biofilm assays, pyrogallol-reduced biofilm formation in Staphylococcus epidermidis ATCC 35984, Staph. epidermidis NRRL-B41021, Staphylococcus aureus USA300, and Staph. aureus Newman, without significantly impairing bacterial viability. Pyrogallol-mediated impairment of biofilm formation was likely due to induction of bacterial oxidative stress, as its effect was greater in catalase-deficient versus WT Staph. aureus, and biofilm production was rescued by exogenous catalase. The effect of pyrogallol on staphylococcal biofilm formation mirrored that of the known oxidant hydrogen peroxide, which also reduced biofilm formation in a dose-dependent manner. CONCLUSIONS: Pyrogallol reduces biofilm formation in S. aureus and Staph. epidermidis in a mechanism involving induction of bacterial oxidative stress.
Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Pirogalol/farmacologia , Catalase/genética , Staphylococcus , Infecções Estafilocócicas/microbiologia , Staphylococcus epidermidis , BiofilmesRESUMO
The present research focuses on the micro-level detection of cobalt ions in biological and environmental samples using a new probe. The probe is a multifunctional symmetrical dipodal molecule with two pyrogallol binding units attached to the malonate scaffold through a propylene spacer. It was synthesized and characterized by 1H NMR, 13C NMR, IR, electronic spectroscopy, and mass spectrometry. The molecule's binding, thermodynamic, and photophysical properties are also described. The designed probe demonstrates an excellent sensing ability for Co(II) based on the ESIPT "OFF-ON" fluorescence mechanism. The experiments explore the high selectivity of the ligand for cobalt sensing over a wide range of metal ions of biological and environmental importance. The fluorescence intensity shows a linear response to Co(II) in 5-100 µM concentration with a detection limit of 8.75 x 10-5 and a 2.65-fold enhancement in the intensity. These results establish its potential application as a fluorescence sensor. The probe is also employed as a colorimetric sensor for the qualitative determination of cobalt ions in DMSO solution. The interesting behavior of the probe motivated us further to study its coordination properties with divalent cobalt in solution. The pre-organized assembly with an appropriate cavity size favors the ligand for an efficient Co(II) encapsulation by coordinating through imine-Ns and aromatic ring-Os donors, giving high formation constants.