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1.
Molecules ; 26(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34279398

RESUMO

The aim of this study was to compare the influence of the extraction method, chemical composition, antimicrobial effects, antioxidant activity, and cytotoxicity on human cells of the non-polar extracts of grape (Vitis labrusca) and blackberry (Rubus fruticosus) seeds. The Soxhlet (Sox), Bligh-Dyer (BD), and ultrasound (US) methods were used for extractions. For blackberry non-polar seed extract, extraction via the BD method showed the highest mean values of total phenolic content (TPC), expressed in milligrams of gallic acid equivalent per 100 mL of non-polar seed extracts (102.37 mg GAE/100 mL), and higher antioxidant activity in relation to the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, expressed in milligrams of gallic acid equivalent per 100 mL of non-polar seed extracts (11.50 mg AAE/100 mL), if compared with the Sox and US extractions. Similar results were obtained for the non-polar grape seed extracts, where BD extraction obtained the highest values for TPC (28.61 mg GAE/100 mL) and DPPH (35.36 mg AAE/100 mL). The type of extraction method had an impact on the composition of fatty acids. Only the non-polar blackberry and grape seed extracts obtained via the Sox method showed some in vitro inhibitory effect against Escherichia coli (IAL 2064) and Staphylococcus aureus (ATCC 13565). Regardless of the extraction method used, the non-polar blackberry and grape seed extracts did not decrease the cell viability (IC50 >1000 µg/mL) of cancer and normal cell lines, thus indicating the relative safety of the extracts. All the seed extracts decreased the generation of reactive oxygen species in the cell lines. Blackberry and grape seed lipid fractions can be utilized as antioxidants, and the extraction methods used cause significant changes in relation to their bioactivity and chemical composition.


Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Extrato de Sementes de Uva/química , Rubus/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/toxicidade , Antioxidantes/farmacologia , Antioxidantes/toxicidade , Escherichia coli/efeitos dos fármacos , Ácidos Graxos/análise , Flavonoides/análise , Extrato de Sementes de Uva/farmacologia , Staphylococcus aureus/efeitos dos fármacos
2.
Molecules ; 26(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34299388

RESUMO

In a project designed to investigate the specific and infraspecific taxa of Matthiola endemic to Sicily (Italy) as new potential sources of bioactive compounds in this work, the infraspecific taxa of Matthiola fruticulosa were studied, namely, subsp. fruticulosa and subsp. coronopifolia. HPLC-PDA/ESI-MS and SPME-GC/MS analyses of hydroalcoholic extracts obtained from the aerial parts of the two subspecies led to the detection of 51 phenolics and 61 volatile components, highlighting a quite different qualitative-quantitative profile. The antioxidant properties of the extracts were explored through in vitro methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH), reducing power and Fe2+ chelating activity assays. The results of the antioxidant tests showed that the extracts possess a different antioxidant ability: particularly, the extract of M. fruticulosa subsp. fruticulosa exhibited higher radical scavenging activity than that of subsp. coronopifolia (IC50 = 1.25 ± 0.02 mg/mL and 2.86 ± 0.05 mg/mL), which in turn displayed better chelating properties (IC50 = 1.49 ± 0.01 mg/mL and 0.63 ± 0.01 mg/mL). Lastly, Artemia salina lethality bioassay was performed for toxicity assessment. The results of the bioassay showed lack of toxicity against brine shrimp larvae for both extracts. The data presented indicate the infraspecific taxa of M. fruticulosa as new and safe sources of antioxidant compounds.


Assuntos
Antioxidantes/toxicidade , Brassicaceae/química , Larva/crescimento & desenvolvimento , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/toxicidade , Animais , Artemia , Larva/efeitos dos fármacos , Sicília , Testes de Toxicidade
3.
Ecotoxicol Environ Saf ; 221: 112450, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34186417

RESUMO

Bisphenol A (BPA) is a widely distributed environmental endocrine disruptor. The accumulation of BPA has been proved that produce various toxic effects both on human and animals. However, the strategies to reduce the damage of BPA on the body and related mechanisms remain to be studied. Coenzyme Q10 (CoQ10), as a powerful antioxidant, is ubiquitous in many eukaryotic cells, which can improve the integrity of lysosomal membrane, lysosomal degradation function and promote autophagy. Here, we examined the ability of CoQ10 to alleviate oxidative stress and apoptosis in BPA-induced damages in C2C12 cells, and how to alleviate it. Our results showed that BPA treatment significantly reduced cell viability, increased the number of cell apoptosis and ROS production, decreased mitochondrial membrane potential, and inhibited the gene expression of mitochondria biogenesis. Moreover, we demonstrated that exposure to BPA increased expression levels of autophagy protein (LC3-II, p62), inhibited autophagy flux, and disrupted the acidic pH environment of lysosomes. Importantly, CoQ10 supplementation effectively restored these abnormalities caused by BPA. CoQ10 significantly decreased the apoptotic incidence and ROS levels, improved mitochondrial membrane potential. Moreover, CoQ10 improved lysosome function and enhanced autophagy flux. Taken together, our results indicate that CoQ10 supplementation is a feasible and effective way to promote the level of autophagy by improving lysosomal function, thereby reducing the apoptosis caused by BPA accumulation. This study aims to provide evidence for the role of CoQ10 in repairing BPA-induced cell damage in clinical practice.


Assuntos
Antioxidantes/toxicidade , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Ubiquinona/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Lisossomos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Ubiquinona/farmacologia
4.
Food Chem Toxicol ; 153: 112268, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34015423

RESUMO

The Tanacetum genus is a big treasure with the presence of biologically-active compounds and members of this genus are widely used for the treatment of several diseases in traditional medicine system. Considering this fact, we aimed to analyze the extracts from Tanacetum vulgare L. in case of chemical profiles and biological effects. Chemical characterization was performed by using UHPLC-HRMS technique and showed the presence of several phytochemical groups (107 compounds were identified, including phenolic acids, flavonoids, terpenoids and fatty acids. Biological abilities were examined by using antioxidant (DPPH, ABTS, FRAP, CUPRAC, metal chelating and phosphomolybdenum assays) and enzyme inhibition (tyrosinase, amylase, glucosidase and cholinesterase) properties. Pharmaco-toxicological investigations were also performed with the aim to identify limits of biocompatibility, anti-oxidant and neuromodulatory effects, in hypothalamic HypoE22 cells. A bioinformatic analysis was also carried to unravel the putative protein-targets for the observed biological effects. Generally, the tested hexane and hydroalcoholic extracts displayed stronger activities in antioxidant and enzyme inhibitory assays, when compared with water. In addition, multivariate analysis was performed to understand the differences in both solvents and plant parts and we clearly observed the separation of these parameters. The extracts (10 µg/mL) also stimulated DAT and inhibited TNFα and BDNF gene expression, in HypoE22 cells. In parallel, the extracts were also able to stimulate norepinephrine release from this cell line. By contrast, in the concentration range 50-100 µg/mL, the extracts reduced the HypoE22 viability, thus demonstrating cytotoxicity at concentrations 5-10 fold higher compared to those effective as neuromodulatory. Our observations manifested that T. vulgare has several beneficial effects and it can be used as a potential natural raw material for designing further health-promoting applications in nutraceutical, cosmeceutical, and pharmaceutical areas.


Assuntos
Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Tanacetum/química , Animais , Antioxidantes/análise , Antioxidantes/química , Antioxidantes/toxicidade , Artemia/efeitos dos fármacos , Linhagem Celular , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/química , Inibidores Enzimáticos/toxicidade , Etanol/química , Flores/química , Hexanos/química , Análise Multivariada , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Compostos Fitoquímicos/toxicidade , Componentes Aéreos da Planta/química , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Caules de Planta/química , Mapas de Interação de Proteínas , Ratos , Solventes/química , Água/química
5.
Food Chem Toxicol ; 153: 112284, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34044082

RESUMO

Aqueous extracts from blackcurrant press cake (BC), Norway spruce bark (NS), Scots pine bark (SP), and sea buckthorn leaves (SB) were obtained using maceration and pressurized hot water and tested for their bioactivities. Maceration provided the extraction of higher dry matter contents, including total phenolics (TPC), anthocyanins, and condensed tannins, which also impacted higher antioxidant activity. NS and SB extracts presented the highest mean values of TPC and antioxidant activity. Individually, NS extract presented high contents of proanthocyanidins, resveratrol, and some phenolic acids. In contrast, SB contained a high concentration of ellagitannins, ellagic acid, and quercetin, explaining the antioxidant activity and antibacterial effects. SP and BC extracts had the lowest TPC and antioxidant activity. However, BC had strong antiviral efficacy, whereas SP can be considered a potential ingredient to inhibit α-amylase. Except for BC, the other extracts decreased reactive oxygen species (ROS) generation in HCT8 and A549 cells. Extracts did not inhibit the production of TNF-alpha in lipopolysaccharide-stimulated THP-1 macrophages but inhibited the ROS generation during the THP-1 cell respiratory burst. The recovery of antioxidant compounds from these by-products is incentivized for high value-added applications.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/toxicidade , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Enterovirus Humano B/efeitos dos fármacos , Química Verde , Hippophae/química , Humanos , Testes de Sensibilidade Microbiana , Picea/química , Pinus sylvestris/química , Casca de Planta/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta/química , Ribes/química
6.
Int J Biol Macromol ; 183: 158-170, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33901559

RESUMO

The influence of protein (sodium caseinate-SC), polysaccharide (maltodextrin-MD; pectin-PC) and their Maillard conjugates (sodium caseinate maltodextrin conjugate-SCMDC; sodium caseinate pectin conjugate-SCPCC) were studied on the physico-chemical and biological properties of eugenol nanoemulsions/powder. The chemical composition was optimized using Taguchi design. The particles size of eugenol nanoemulsions with SC, MD, PC, SCMDC and SCPCC were 104.6, 323.5, 1872, 181.7, and 454.4 nm, respectively while their zeta potentials were -31.2, -28.5, -21.4, -40.1 and -25.1 mV, respectively. Turbidity studies revealed higher stability of nanoemulsion prepared with Maillard conjugate (SCMDC) compared to protein or polysaccharides alone. The dispersion of SCMDC eugenol nanoparticles in buffer was prepared to study its stability at different pH (3.0, 5.0, and 7.0) and temperature (4°, 37°, 60 °C) range. In-vitro enzymatic release study showed 31 and 74% release of eugenol after 6 h at pH 2.4 and 7.4, respectively. In vitro antioxidant capacity of SCMDC encapsulated eugenol was higher than native eugenol, as demonstrated by free radical scavenging assays. In comparison to native eugenol, E:SCMDC eugenol showed reduced toxicity. These findings suggested that nanoencapsulated eugenol (E:SCMDC) have a huge potential in nutraceutical and therapeutic applications.


Assuntos
Antioxidantes/química , Caseínas/química , Portadores de Fármacos , Eugenol/química , Nanopartículas , Azeite de Oliva/química , Pectinas/química , Polissacarídeos/química , Antioxidantes/farmacologia , Antioxidantes/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Emulsões , Eugenol/farmacologia , Eugenol/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Reação de Maillard , Temperatura
7.
Int J Biol Macromol ; 182: 977-986, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33887289

RESUMO

Lignin is a complex phenolic biopolymer present in plant cell walls and a by-product of the cellulose pulping industry. Lignin has functional properties, such as antioxidant activity, that make it a potential natural active ingredient for health-care products. However, not all safety aspects of lignin fractions have been adequately investigated. Herein, we evaluated the antioxidant and genotoxic potential of two hardwood kraft lignins (F3 and F5). The chemical characterization of F3 and F5 demonstrated their thermal stability and the presence of different phenolic units, while the DPPH assay confirmed the antioxidant activity of these lignin fractions. Despite being antioxidants in the DPPH assay, F3 and F5 were capable of generating intracellular reactive oxygen species (ROS) and subsequently causing oxidative DNA damage (Comet assay) in HepG2 cells. The biological relevance of the DPPH assay might be uncertain in some cases; therefore, we suggest combining in chemico tests with biological system-based tests to determine efficacy and safety levels of lignins and define appropriate applications of lignins for consumer products. Moreover, kraft lignins obtained by acid precipitation may pose risks to human health; however, as genotoxicity is not the sole endpoint of toxicity required in hazard assessments, additional toxicological evaluations are needed.


Assuntos
Antioxidantes/química , Lignina/química , Mutagênicos/química , Antioxidantes/toxicidade , Dano ao DNA , Células Hep G2 , Humanos , Lignina/toxicidade , Mutagênicos/toxicidade , Estresse Oxidativo
8.
Food Chem ; 353: 129488, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33714793

RESUMO

Synthetic phenolic antioxidants can interact with peroxides produced by food. This paper reviews correlation between BHA, BHT and TBHQ metabolism and harms they cause and provides a theoretical basis for rational use of BHA, BHT and TBHQ in food, and also put some attention on the transformation and metabolic products of PG. We introduce BHA, BHT, TBHQ, PG and their possible metabolic pathways, and discuss possible harms and their specific mechanisms responsible. Excessive addition or incorrect use of synthetic phenolic antioxidants results in carcinogenicity, cytotoxicity, oxidative stress induction and endocrine disrupting effects, which warrant attention. BHA carcinogenicity is related to production of metabolites TBHQ and TQ, and cytotoxic effect of BHA is the main cause of apoptosis induction. BHT carcinogenicity depends on DNA damage degree, and tumour promotion is mainly related to production of quinone methylation metabolites. TBHQ carcinogenicity is related to induction of metabolite TQ and enzyme CYP1A1.


Assuntos
Antioxidantes/síntese química , Fenóis/química , Animais , Antioxidantes/metabolismo , Antioxidantes/toxicidade , Apoptose/efeitos dos fármacos , Hidroxianisol Butilado/química , Hidroxianisol Butilado/metabolismo , Hidroxianisol Butilado/toxicidade , Hidroxitolueno Butilado/química , Hidroxitolueno Butilado/metabolismo , Hidroxitolueno Butilado/toxicidade , Aditivos Alimentares/química , Aditivos Alimentares/metabolismo , Aditivos Alimentares/toxicidade , Humanos , Hidroquinonas/química , Hidroquinonas/metabolismo , Hidroquinonas/toxicidade
9.
Eur J Med Chem ; 215: 113278, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33662757

RESUMO

Alzheimer's disease (AD) is an age-related multifactorial neurodegenerative disorder characterized by severe central cholinergic neuronal loss, gradually contributing to cognitive dysfunction and impaired motor activity, resulting in the brain's cell death at the later stages of AD. Although the etiology of AD is not well understood, however, several factors such as oxidative stress, deposition of amyloid-ß (Aß) peptides to form Aß plaques, intraneuronal accumulation of hyperphosphorylated tau protein, and low level of acetylcholine are thought to play a major role in the pathogenesis of AD. There is practically no drug for AD treatment that can address the basic factors responsible for the neurodegeneration and slow down the disease progression. The currently available therapies for AD in the market focus on providing only symptomatic relief without addressing the aforesaid basic factors responsible for the neurodegeneration. Ferulic acid (FA) is a phenol derivative from natural sources and serves as a potential pharmacophore that exerts multiple pharmacological properties such as antioxidant, neuroprotection, Aß aggregation modulation, and anti-inflammatory. Several FA based hybrid analogs are under investigation as a multi-target directed ligand (MTDLs) to develop novel hybrid compounds for the treatment of AD. In the present review article, we are focused on the critical pathogenic factors responsible for the onset of AD followed by the developments of FA pharmacophore-based hybrids compounds as a novel multifunctional therapeutic agent to address the limitations associated with available treatment for AD. The rationale behind the development of these compounds and their pharmacological activities in particular to their ChE inhibition (ChEI), neuroprotection, antioxidant property, Aß aggregation modulation, and metal chelation ability, are discussed in detail. We have also discussed the discovery of caffeic and cinnamic acids based MTDLs for AD. This review paper provides an in-depth insight into the research progress and current status of these novel therapeutics in AD and prospects for developing a druggable molecule with desired pharmacological affinity and reduced toxicity for the management of AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Ácidos Cumáricos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/toxicidade , Linhagem Celular Tumoral , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/toxicidade , Humanos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos
10.
J Ethnopharmacol ; 272: 113941, 2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-33610703

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Syagrus coronata, popularly known as licuri, is a palm native to caatingas. The fixed oil extract of licuri nuts is used by the population of Northeast Brazil for therapeutic purposes, including as an antifungal, anti-inflammatory, and a cicatrizant agent. However, there is no scientific information on the possible harmful health effects of the oil and hence its medicinal usability is unknown. AIM OF THE STUDY: We aimed to analyze the biological safety and possible antioxidant activity of fixed S. Coronata oil. MATERIALS AND METHODS: Chemical analysis of the oil was performed using gas chromatography with flame ionization detection (CG-FID). The cytotoxicity of varying concentrations of the oil (12.5, 25, 50, 100, and 200 µg/mL) was evaluated using the tetrazolium reduction assay in three cell lines: HEK-293 kidney embryonic cells, J774.A1 macrophages, and the tumor line Sarcoma-180 (S-180). Oral toxicity, genotoxicity, and mutagenicity tests were performed in mice which were administered a single dose of 2000 mg/kg of fixed licuri oil, by gavage. For acute toxicity tests, changes in blood and biochemical parameters, behavior, and weight were analyzed; histomorphometric analyses of the liver, kidney, and spleen were also performed. The comet assay and micronucleus (MN) test were performed to analyze genotoxicity. The antioxidant potential was assessed by the total antioxidant capacity (AAT) and DPPH elimination activity. RESULTS: Licuri oil consists predominantly of saturated fatty acids, and lauric acid is the major compound. The highest concentrations of the oil showed low levels of cytotoxicity; however, LC50 was not reached in any of the tests. The acute toxicity study did not reveal any evidence of adverse effects in animals treated with oil; biochemical investigation of blood showed a decrease in blood concentration of total proteins and uric acid. The kidneys, spleen, and liver showed no morphological changes indicative of a pathological process. Genotoxic or mutagenic activity was not detected through both the comet assay and MN test. In addition, the oil showed low antioxidant activity in both methods. CONCLUSION: Licuri oil from the stem of S. coronata did not present significant toxic effects as well as absence of genetic damage when administered orally. Future studies are needed to investigate its pharmacological potential.


Assuntos
Arecaceae/química , Dano ao DNA/efeitos dos fármacos , Óleo de Palmeira/farmacologia , Administração Oral , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Antioxidantes/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Ácidos Graxos/análise , Humanos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Testes para Micronúcleos , Testes de Mutagenicidade , Óleo de Palmeira/administração & dosagem , Óleo de Palmeira/toxicidade , Baço/efeitos dos fármacos , Testes de Toxicidade Aguda
11.
J Ethnopharmacol ; 272: 113940, 2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-33631275

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia species are known to have anti-inflammatory properties, and are traditionally used for healing purposes. Salvia verbenaca is an Algerian plant used for healing wounds and ulcers. AIM OF THE STUDY: This work aims to assess the acute and subacute safety of S. verbenaca and its possible anti-inflammatory activity as a mechanism contributing to its traditional applications. MATERIALS AND METHODS: Lethal toxicity of S. verbenaca hydromethanolic extract was evaluated against Artemia salina larvae, while acute and subacute toxicity were orally tested on mice. The anti-inflammatory activity was screened ex vivo using membrane stabilization and in vivo using xylene induced ear edema as an acute inflammation model. The antiradical, reducing power and iron chelating activities of S. verbenaca were also investigated in vitro, and phenolic compounds were determined using UHPLC-DAD-ESI-MSn. RESULTS: Salvia verbenaca extract contained high amounts of phenolic compounds (206 µg GAE/mg extract). The in vitro antioxidant activity showed promising radical scavenging ability, iron chelating (IC50: 189 µg/mL), reducing power and strong anti-lipid-peroxidation effect (IC50: 111 µg/mL). The extract had potential cytotoxic effect against Artemia salina larvae (LC50: 30 µg/mL), but did not exhibit any acute/subacute toxicity effect on mice. Salvia verbenaca inhibited hypotonic and heat induced hemolysis and also reduced 50% of xylene induced ear edema at 600 mg/kg bw. Rosmarinic acid and caffeoylmalic acid were identified as the major compounds. CONCLUSION: Salvia verbenaca hydromethanolic extract was found to be safe at acute and subacute levels. Its in vitro/in vivo antioxidant activity, membrane stabilizing properties and anti-inflammatory activity may be an important aspect of its wound healing and anti-ulcer traditional use.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Salvia/química , Animais , Anti-Inflamatórios/toxicidade , Antioxidantes/toxicidade , Edema/induzido quimicamente , Edema/tratamento farmacológico , Rim/efeitos dos fármacos , Larva/efeitos dos fármacos , Fígado/efeitos dos fármacos , Camundongos , Fenóis/análise , Fenóis/toxicidade , Componentes Aéreos da Planta/química , Extratos Vegetais/análise , Extratos Vegetais/toxicidade , Xilenos/toxicidade
12.
Regul Toxicol Pharmacol ; 121: 104887, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33556417

RESUMO

Tumor data from rodent bioassays are used for cancer hazard classification with wide-ranging consequences. This paper presents a case study of the synthetic antioxidant butylated hydroxyanisole (BHA), which IARC classified as Group 2B ("possibly carcinogenic to humans") on the basis of forestomach tumors in rodents following chronic dietary exposure to high levels. IARC later determined that the mechanism by which BHA induces forestomach tumors is not relevant to humans; however, the classification has not been revoked. BHA was listed on California Proposition 65 as a direct consequence of the IARC classification, and there is widespread concern among consumers regarding the safety of BHA driven by the perception that it is a carcinogen. While many regulatory agencies have established safe exposure limits for BHA, the IARC classification and Proposition 65 listing resulted in the addition of BHA to lists of substances banned from children's products and products seeking credentials such as EPA's Safer Choice program, as well as mandatory product labeling. Classifications have consequences that many times pre-empt the ability to conduct an exposure-based risk-based assessment., It is imperative to consider human relevance of both the endpoint and exposure conditions as fundamental to hazard identification.


Assuntos
Antioxidantes/classificação , Hidroxianisol Butilado/classificação , Carcinógenos/classificação , Aditivos Alimentares/classificação , Animais , Antioxidantes/toxicidade , Hidroxianisol Butilado/toxicidade , Carcinógenos/toxicidade , Aditivos Alimentares/toxicidade , Abastecimento de Alimentos , Humanos , Medição de Risco
13.
Life Sci ; 271: 119139, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33539914

RESUMO

AIMS: Complicated mechanisms in cancer cells have been restricting the medicinal value of resveratrol (Res). The mechanisms by which Res exerts its anti-tumor activity in lung cancer cells have diverged among reports in recent years, whether cells choose to undergo autophagic cell death or apoptosis remains controversial. Yet, whether Res-induced autophagic cell death transforms into apoptosis is still unknown, and by which autophagy regulates programmed cell death is still undefined. MAIN METHODS: Here, A549 cells were treated with Res to investigate the mechanisms of autophagy and apoptosis using western blot, immunofluorescence staining for LC3B. KEY FINDINGS: Non-canonical autophagy was induced by Res-treatment in a Beclin-1- and ATG5-independent manner, with apoptosis being activated simultaneously. Autophagy induced by Res was activated by rapamycin with decreased apoptosis, suggesting that autophagy may serve as a protective pathway in cells. Mitophagy was found to be induced by Res using fluorescence co-localization of mitochondria with lysosomes. Subsequently, it was identified that mitophagy was mediated by LC3B/p62 interaction and could be inhibited by LC3B knockout and p62 knockdown following increased apoptosis. SIGNIFICANCE: In conclusion, the current results demonstrate that Res-induced non-canonical autophagy in A549 lung cancer cells with apoptosis activation simultaneously, while LC3B/p62-mediated mitophagy protects tumor cells against apoptosis, providing novel mechanisms about the critical role of mitophagy in regulating cell fate.


Assuntos
Antioxidantes/toxicidade , Apoptose/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Mitofagia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Resveratrol/toxicidade , Células A549 , Apoptose/fisiologia , Citoproteção/efeitos dos fármacos , Citoproteção/fisiologia , Relação Dose-Resposta a Droga , Humanos , Mitofagia/fisiologia , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia
14.
Molecules ; 26(3)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525350

RESUMO

Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions.


Assuntos
Cinetina/farmacologia , Cinetina/toxicidade , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/toxicidade , Animais , Antioxidantes/fisiologia , Antioxidantes/toxicidade , Biomarcadores/metabolismo , Creatinina/metabolismo , Citocininas/metabolismo , Glucose/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/toxicidade , Ratos , Receptores Purinérgicos P1/metabolismo
15.
Molecules ; 26(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540783

RESUMO

In this study, we investigated the bioactive potential (antibacterial and antioxidant), anticancer activity and detailed phytochemical analysis of Selaginellarepanda (S. repanda) ethanolic crude extract for the very first time using different in vitro approaches. Furthermore, computer-aided prediction of pharmacokinetic properties and safety profile of the identified phytoconstituents were also employed in order to provide some useful insights for drug discovery. S. repanda, which is a rich source of potent natural bioactive compounds, showed promising antibacterial activity against the tested pathogenic bacteria (S. aureus, P. aeruginosa, E. coli and S. flexneri). The crude extract displayed favorable antioxidant activity against both 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 231.6 µg/mL) and H2O2 (IC50 = 288.3 µg/mL) molecules. S. repanda also showed favorable and effective anticancer activity against all three malignant cancer cells in a dose/time dependent manner. Higher activity was found against lung (A549) (IC50 = 341.1 µg/mL), followed by colon (HCT-116) (IC50 = 378.8 µg/mL) and breast (MCF-7) (IC50 = 428.3 µg/mL) cancer cells. High resolution-liquid chromatography-mass spectrometry (HR-LC-MS) data of S. repanda crude extract revealed the presence of diverse bioactive/chemical components, including fatty acids, alcohol, sugar, flavonoids, alkaloids, terpenoids, coumarins and phenolics, which can be the basis and major cause for its bioactive potential. Therefore, achieved results from this study confirmed the efficacy of S. repanda and a prospective source of naturally active biomolecules with antibacterial, antioxidant and anticancer potential. These phytocompounds alone with their favorable pharmacokinetics profile suggests good lead and efficiency of S. repanda with no toxicity risks. Finally, further in vivo experimental investigations can be promoted as probable candidates for various therapeutic functions, drug discovery and development.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Selaginellaceae/química , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Antioxidantes/toxicidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Humanos , Neoplasias Pulmonares/patologia , Extratos Vegetais/farmacocinética , Extratos Vegetais/toxicidade
16.
Int J Mol Sci ; 22(2)2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33435390

RESUMO

The evaluation of antioxidant compounds that counteract the mutagenic effects caused by the direct action of reactive oxygen species on DNA molecule is of considerable interest. Therefore, a series of 2,3-substituted quinazolinone derivatives (Q1-Q8) were investigated by different assays, and the relationship between their biological properties and chemical structure was examined. Genotoxicity and the potential DNA-protective effects of Q1-Q8 were evaluated by comet assay and DNA topology assay. Antioxidant activity was examined by DPPH-radical-scavenging, reducing-power, and total antioxidant status (TAS) assays. The cytotoxic effect of compounds was assessed in human renal epithelial cells (TH-1) and renal carcinoma cells (Caki-1) by MTT assay. Analysis of the structure-activity relationship disclosed significant differences in the activity depending on the substitution pattern. Derivatives Q5-Q8, bearing electron-donating moieties, were the most potent members of this series. Compounds were not genotoxic and considerably decreased the levels of DNA lesions induced by oxidants (H2O2, Fe2+ ions). Furthermore, compounds exhibited higher cytotoxicity in Caki-1 compared to that in TH-1 cells. Substantial antioxidant effect and DNA-protectivity along with the absence of genotoxicity suggested that the studied quinazolinones might represent potential model structures for the development of pharmacologically active agents.


Assuntos
Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Dano ao DNA/efeitos dos fármacos , Quinazolinonas/farmacologia , Antimutagênicos/química , Antimutagênicos/toxicidade , Antioxidantes/química , Antioxidantes/toxicidade , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA/genética , Humanos , Peróxido de Hidrogênio/toxicidade , Mutagênicos/toxicidade , Oxidantes/toxicidade , Quinazolinonas/química , Quinazolinonas/toxicidade , Relação Estrutura-Atividade
17.
Int J Environ Health Res ; 31(2): 148-159, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31257910

RESUMO

This study aims to perform a bioactive analysis of five mushrooms collected in south of Brazil. The total phenol content of the extracts was equivalent to the antioxidant activity by ACAP assay. All extracts were able to inhibit the growth of Acinetobacter baumanni, and Auricularia auricula and Lactarius deliciosus extract showed the best antibacterial activity. In addition, no extract showed cytotoxic activity against VERO cells at the highest concentration evaluated (2500 µg/mL). Our results showed better antioxidant activity through the inhibition of the oxidation via peroxyl radical. It can be observed that all extracts were active against A. baumanni, and even moderately, all extracts could be inhibited of at least one of the bacteria used in the study. Added for these, the aqueous extracts showed no toxicity in VERO cells, highlighting the importance of research about the active compounds of mushrooms of the region.


Assuntos
Agaricales/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Agaricales/crescimento & desenvolvimento , Agaricales/metabolismo , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/toxicidade , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Brasil , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Células Vero
18.
Environ Toxicol ; 36(4): 451-459, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33107697

RESUMO

d-Galactosamine (d-GalN) is a well-known toxin that causes many metabolic and morphological abnormalities resulting in advanced renal failure and liver damage. Occupational exposure to low-level ionizing radiation (<1 Gy) was shown to enhance cell protection via attenuating an established inflammatory process. The present study was therefore aimed to investigate the protective impact of Amphora coffaeiformis extract and low dose gamma radiation against d-GalN induced renal damage in rats. Forty-eight adult male Swiss albino rats were distributed equally into eight groups. The measurements included antioxidants activities (superoxide dismutase, catalase and glutathione peroxidase) as well as lipid peroxidation level in kidney tissue. Also, kidney function tests and inflammatory markers (tumor necrosis factor alpha and nuclear factor kappa-light-chain-enhancer of activated B cells) were measured. Additionally, relative quantification of kidney nuclear factor erythroid 2-related factor 2 (Nrf-2) gene was estimated. Histopathological examination was also performed in kidney tissue. The results revealed decreases in antioxidant activities and downregulation of Nrf-2 expression accompanied by increases in lipid peroxidation level, kidney function tests and inflammatory markers in d-GaIN group. The treatment with Amphora algal extract and low dose gamma radiation ameliorated the previous measurements which were harmony with histopathological findings. In conclusion, A coffaeiformis extract and low dose gamma radiation provided marked functional and histological effects in the treating acute renal damage induced by d-GalN in rats.


Assuntos
Antioxidantes/farmacologia , Diatomáceas/química , Galactosamina/toxicidade , Rim/efeitos dos fármacos , Rim/imunologia , Radiação Ionizante , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Inflamação , Rim/patologia , Rim/efeitos da radiação , Testes de Função Renal , Dose Letal Mediana , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Masculino , Fator 2 Relacionado a NF-E2/genética , Doses de Radiação , Ratos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Irradiação Corporal Total
19.
J Biosci Bioeng ; 131(2): 176-182, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33268318

RESUMO

Celastrol is a quinone-methide triterpenoid isolated from the root extracts of Tripterygium wilfordii (Thunder god vine). Although celastrol possesses multiple bioactivities, the potent toxicity and rare solubility in water hinder its clinical application. Biotransformation of celastrol using either whole cells or purified enzymes to form less toxic and more soluble derivatives has been proven difficult due to its potent antibiotic and enzyme-conjugation property. The present study evaluated biotransformation of celastrol by four glycosyltransferases from Bacillus species and found one glycosyltransferase (BsGT110) from Bacillus subtilis with significant activity toward celastrol. The biotransformation metabolite was purified and identified as celastrol-29-O-ß-glucoside by mass and nuclear magnetic resonance spectroscopy. Celastrol-29-O-ß-glucoside showed over 53-fold higher water solubility than celastrol, while maintained 50% of the free radical scavenging activity of celastrol. When using zebrafish as the in vivo animal model, celastrol-29-O-ß-glucoside exhibited 50-fold less toxicity than celastrol. To our knowledge, the present study is not only the first report describing the biotransformation of celastrol, but also the first one detailing a new compound, celastrol-29-O-ß-glucoside, that is generated in the biotransformation process. Moreover, celastrol-29-O-ß-glucoside may serve as a potential candidate in the future medicine application due to its higher water solubility and lower toxicity.


Assuntos
Antioxidantes/química , Antioxidantes/metabolismo , Bacillus subtilis/enzimologia , Glucosídeos/química , Glucosídeos/metabolismo , Glicosiltransferases/metabolismo , Triterpenos/metabolismo , Animais , Antioxidantes/toxicidade , Bacillus subtilis/metabolismo , Biotransformação , Glucosídeos/toxicidade , Solubilidade
20.
Science ; 371(6525): 185-189, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33273063

RESUMO

In U.S. Pacific Northwest coho salmon (Oncorhynchus kisutch), stormwater exposure annually causes unexplained acute mortality when adult salmon migrate to urban creeks to reproduce. By investigating this phenomenon, we identified a highly toxic quinone transformation product of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a globally ubiquitous tire rubber antioxidant. Retrospective analysis of representative roadway runoff and stormwater-affected creeks of the U.S. West Coast indicated widespread occurrence of 6PPD-quinone (<0.3 to 19 micrograms per liter) at toxic concentrations (median lethal concentration of 0.8 ± 0.16 micrograms per liter). These results reveal unanticipated risks of 6PPD antioxidants to an aquatic species and imply toxicological relevance for dissipated tire rubber residues.


Assuntos
Antioxidantes/toxicidade , Benzoquinonas/toxicidade , Exposição Ambiental , Oncorhynchus kisutch/fisiologia , Fenilenodiaminas/toxicidade , Borracha/toxicidade , Animais , Noroeste dos Estados Unidos , Borracha/química
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