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1.
Cells ; 13(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891033

RESUMO

Helicobacter pylori has been implicated in various gastrointestinal disorders, including functional dyspepsia. This study aimed to compare the anti-H. pylori activity and gastroprotective effects of three typical herbal formulas used for gastrointestinal disorders in Korea: Shihosogan-tang (ST), Yijung-tang (YT), and Pyeongwi-san (PS). Firstly, we assessed the total phenolic and flavonoid contents, as well as the antioxidative capacity. Additionally, we evaluated the antibacterial effect on H. pylori using an ammonia assay, minimum inhibitory concentration (MIC) test, and the disk agar diffusion method. Furthermore, we examined alterations in the gene expression of tight junction proteins, pro-inflammatory cytokines, and cellular vacuolation using an AGS cell model infected with H. pylori. While ST exhibited a higher total phenolic content, superior free radical scavenging, and inhibition of H. pylori compared to YT and PS, YT more evidently inhibited gastric cellular morphological changes such as vacuolation. All formulations significantly ameliorated changes in inflammatory and gastric inflammation-related genes and cellular morphological alterations induced by H. pylori infection. Overall, the present in vitro study suggests that all three herbal formulas possess potential for ameliorating gastrointestinal disorders, with ST relatively excelling in inhibiting H. pylori infection and inflammation, while YT potentially shows greater efficacy in directly protecting the gastric mucosa.


Assuntos
Dispepsia , Helicobacter pylori , Helicobacter pylori/efeitos dos fármacos , Dispepsia/tratamento farmacológico , Dispepsia/patologia , Humanos , Antibacterianos/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Antioxidantes/farmacologia , Flavonoides/farmacologia , Testes de Sensibilidade Microbiana , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
2.
Mar Drugs ; 22(4)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38667771

RESUMO

Algae are used as safe materials to fabricate novel nanoparticles to treat some diseases. Marine brown alga Sargassum vulgare are used to fabricate silver nanoparticles (Sv/Ag-NPs). The characterization of Sv/Ag-NPs was determined by TEM, EDX, Zeta potential, XRD, and UV spectroscopy. The Sv/Ag-NPs were investigated as antioxidant, anticancer, and antibacterial activities against Gram-positive bacteria Bacillus mojavensis PP400982, Staphylococcus caprae PP401704, Staphylococcus capitis PP402689, and Staphylococcus epidermidis PP403851. The activity of the Sv/Ag-NPs was evaluated as hepatoprotective in vitro in comparison with silymarin. The UV-visible spectrum of Sv/Ag-NPs appeared at 442 nm; the size of Sv/Ag-NPs is in range between 6.90 to 16.97 nm, and spherical in shape. Different concentrations of Sv/Ag-NPs possessed antioxidant, anticancer activities against (HepG-2), colon carcinoma (HCT-116), cervical carcinoma (HeLa), and prostate carcinoma (PC-3) with IC50 50.46, 45.84, 78.42, and 100.39 µg/mL, respectively. The Sv/Ag-NPs induced the cell viability of Hep G2 cells and hepatocytes treated with carbon tetrachloride. The Sv/Ag-NPs exhibited antibacterial activities against Staphylococcus caprae PP401704, Staphylococcus capitis PP402689, and Staphylococcus epidermidis PP403851. This study strongly suggests the silver nanoparticles derived from Sargassum vulgare showed potential hepato-protective effect against carbon tetrachloride-induced liver cells, and could be used as anticancer and antibacterial activities.


Assuntos
Antibacterianos , Antineoplásicos , Antioxidantes , Nanopartículas Metálicas , Sargassum , Prata , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Prata/farmacologia , Prata/química , Antioxidantes/farmacologia , Antioxidantes/química , Nanopartículas Metálicas/química , Sargassum/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Testes de Sensibilidade Microbiana , Células Hep G2 , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Staphylococcus epidermidis/efeitos dos fármacos , Células HeLa
3.
Sci Rep ; 12(1): 2195, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35140281

RESUMO

The present study aimed to assess the toxic effects of pendimethalin herbicide and protective role of curcumin using the Allium test on cytological, biochemical and physiological parameters. The effective concentration (EC50) of pendimethalin was determined at 12 mg/L by the root growth inhibition test as the concentration reducing the root length by 50%. The roots of Allium cepa L. was treated with tap water (group I), 5 mg/L curcumin (group II), 10 mg/L curcumin (group III), 12 mg/L pendimethalin (group IV), 12 mg/L pendimethalin + 5 mg/L curcumin (group V) and 12 mg/L pendimethalin + 10 mg/L curcumin (group VI). The cytological (mitotic index, chromosomal abnormalities and DNA damage), physiological (rooting percentage, root length, growth rate and weight gain) and oxidative stress (malondialdehyde level, superoxide dismutase level, catalase level and glutathione reductase level) indicators were determined after 96 h of treatment. The results revealed that pendimethalin treatment reduced rooting percentage, root length, growth rate and weight gain whereas induced chromosomal abnormalities and DNA damage in roots of A. cepa L. Further, pendimethalin exposure elevated malondialdehyde level followed by antioxidant enzymes. The activities of superoxide dismutase and catalase were up-regulated and glutathione reductase was down-regulated. The molecular docking supported the antioxidant enzymes activities result. However, a dose-dependent reduction of pendimethalin toxicity was observed when curcumin was supplied with pendimethalin. The maximum recovery of cytological, physiological and oxidative stress parameters was recorded at 10 mg/L concentration of curcumin. The correlation studies also revealed positive relation of curcumin with rooting percentage, root length, weight gain, mitotic activity and glutathione reductase enzyme level while an inverse correlation was observed with chromosomal abnormalities, DNA damage, superoxide dismutase and catalase enzyme activities, and lipid peroxidation indicating its protective effect.


Assuntos
Compostos de Anilina/toxicidade , Curcumina/farmacologia , Herbicidas/toxicidade , Cebolas/genética , Raízes de Plantas/genética , Substâncias Protetoras/farmacologia , Aberrações Cromossômicas/efeitos dos fármacos , Correlação de Dados , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Peroxidação de Lipídeos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Cebolas/efeitos dos fármacos , Cebolas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/efeitos dos fármacos , Oxirredutases/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo
4.
Int J Mol Sci ; 22(24)2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34948423

RESUMO

Depression associated with poor general medical condition, such as post-stroke (PSD) or post-myocardial infarction (PMID) depression, is characterized by resistance to classical antidepressants. Special treatment strategies should thus be developed for these conditions. Our study aims to investigate the mechanism of action of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17), a recently designed thiadiazine derivative with putative neuro- and cardioprotective and antidepressant-like effects, using combined in silico (for prediction of the molecular binding mechanisms), ex vivo (for assessment of the neural excitability using c-Fos immunocytochemistry), and in vivo (for direct examination of the neuronal excitability) methodological approaches. We found that the predicted binding affinities of L-17 to serotonin (5-HT) transporter (SERT) and 5-HT3 and 5-HT1A receptors are compatible with selective 5-HT serotonin reuptake inhibitors (SSRIs) and antagonists of 5-HT3 and 5-HT1A receptors, respectively. L-17 robustly increased c-Fos immunoreactivity in the amygdala and decreased it in the hippocampus. L-17 dose-dependently inhibited 5-HT neurons of the dorsal raphe nucleus; this inhibition was partially reversed by the 5-HT1A antagonist WAY100135. We suggest that L-17 is a potent 5-HT reuptake inhibitor and partial antagonist of 5-HT3 and 5-HT1A receptors; the effects of L-17 on amygdaloid and hippocampal excitability might be mediated via 5-HT, and putatively mediate the antidepressant-like effects of this drug. Since L-17 also possesses neuro- and cardioprotective properties, it can be beneficial in PSD and PMID. Combined in silico predictions with ex vivo neurochemical and in vivo electrophysiological assessments might be a useful strategy for early assessment of the efficacy and neural mechanism of action of novel CNS drugs.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Hidrazinas/farmacologia , Infarto do Miocárdio/complicações , Acidente Vascular Cerebral/complicações , Animais , Antidepressivos/uso terapêutico , Simulação por Computador , Depressão/etiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hidrazinas/uso terapêutico , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Wistar , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Receptores 5-HT3 de Serotonina/efeitos dos fármacos , Antagonistas do Receptor 5-HT1 de Serotonina , Antagonistas do Receptor 5-HT3 de Serotonina , Proteínas da Membrana Plasmática de Transporte de Serotonina/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia
5.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 142-146, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817355

RESUMO

Present research project was an attempt to explore the functional/nutraceutical worth of guava leaves from two locally grown varieties (Ruby & Safeda). For the purpose, guava leaves extract was fed to experimental male Sprague Dawley rats to explore the nutraceutical potential of guava leaves against hepatotoxicity. Two studies were performed on two types of rats i.e. study I (normal rats), study II (hepatotoxic rats). In both studies, 250 mg/kg each of pink guava leaves extracts (T1) and white guava leaves extracts (T2) was added in the feed. Feed intake and body weights of the rats were recorded. At the end of the first and eighth week of study, the blood samples of the rats were analyzed to check the effect of guava leaves extracts on renal functioning (Alkaline Phosphatase, Alanine Transaminase and Aspartate Transaminase) as well as liver functioning parameters including urea and creatinine. In both studies, comparatively higher feed consumption was observed in the control group than the rest of the treatments. At the end of study I, the highest weight (207±9.21 g) was observed in T0 whereas, during study II, the maximum value (202±5.58 g) was found in T2 (rats consuming white guava leaves extract) that indicates its effectiveness against hepatotoxicity. Regarding renal functioning tests, pink guava leaves were more effective in decreasing urea and creatinine levels in rats as compared to the white guava leaves in both study plans. Likewise, in each of study trial, pink guava leaves were more effective in reducing AST, ALT and ALP than white guava leaves and control. From the present investigation, it is deduced that guava leaves were effective against hepatotoxicity.


Assuntos
Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Psidium/química , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Rim/metabolismo , Rim/fisiologia , Fígado/metabolismo , Fígado/fisiologia , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Psidium/classificação , Ratos Sprague-Dawley , Especificidade da Espécie
6.
Sci Rep ; 11(1): 15681, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344953

RESUMO

In South Korea, it has been found that biocides used to control and eliminate harmful organisms are used as humidifier disinfectants and cause lung disease in users. Hence, efforts have been focused on studying the toxicity of biocides in workers who handle them. The purpose of this study was to evaluate the effects of inhalation exposure to sodium dichloroisocyanurate (NaDCC) to protect the health of workers handling NaDCC. F344 rats were exposed to 0.8-, 4-, and 20-mg/m3 of NaDCC for 6 h per day, 5 days per week for 14 days, and the recovery period after exposure was 14 days. In the 20-mg/m3-exposure group, we observed a decrease in food intake in females, a weight loss in males, and a decrease in partially active thromboplastin time in males and females 2 weeks after exposure. We noted a decrease in white blood cells in males in the 4- and 20-mg/m3-exposed groups. Both males and females in the 20-mg/m3 group and males in the 4-mg/m3 group showed irritation in the larynx related to test substance exposure. However, these findings were not observed in the recovery group. The main target organs affected by repeated 2-week inhalation exposure to NaDCC were the nasal cavity and larynx in the upper respiratory tract. The No Observed Adverse Effect Level (NOAEL) was considered to be 0.8 mg/m3 because effects related to NaDCC exposure were observed even at of 4 mg/m3, and these effects were found to be reversible.


Assuntos
Desinfetantes/química , Umidificadores , Exposição por Inalação , Saúde Ocupacional , Triazinas/química , Animais , Biomarcadores , Fenômenos Químicos , Desinfetantes/administração & dosagem , Feminino , Testes Hematológicos , Humanos , Masculino , Tamanho da Partícula , Substâncias Protetoras , Ratos , Triazinas/administração & dosagem
7.
Cancer Med ; 10(15): 5347-5357, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34184420

RESUMO

PURPOSE: Colorectal cancer (CRC) diagnosis is associated with high mortality in the United States and thus warrants the study of novel treatment approaches. Vascular changes are well observed in cancers and evidence indicates that antihypertensive (AH) medications may interfere with both tumor vasculature and in recruiting immune cells to the tumor microenvironment based on preclinical models. Extant literature also shows that AH medications are correlated with improved survival in some forms of cancer. Thus, this study sought to explore the impact of AH therapies on CRC outcomes. PATIENTS AND METHODS: This study was a non-interventional, retrospective analysis of patients aged 65 years and older with CRC diagnosed from January 1, 2007 to December 31st, 2012 in the Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. The association between AH drug utilization on AJCC stage I-III CRC mortality rates in patients who underwent treatment for cancer was examined using Cox proportional hazards models. RESULTS: The study cohort consisted of 13,982 patients diagnosed with CRC. Adjusted Cox proportional hazards regression showed that among these patients, the use of AH drug was associated with decreased cancer-specific mortality (HR: 0.79, 95% CI: 0.75-0.83). Specifically, ACE inhibitors (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.87), beta-blockers (HR: 0.87, 95% CI: 0.84-0.91), and thiazide diuretics (HR: 0.83, 95% CI: 0.80-0.87) were found to be associated with decreased mortality. An association was also found between adherence to AH therapy and decreased cancer-specific mortality (HR: 0.94, 95% CI: 0.90-0.98). CONCLUSION: Further research needs to be performed, but AH medications may present a promising, low-cost pathway to supporting CRC treatment for stage I-III cancers.


Assuntos
Anti-Hipertensivos/uso terapêutico , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Neoplasias do Colo/irrigação sanguínea , Intervalos de Confiança , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Masculino , Medicare , Adesão à Medicação , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Substâncias Protetoras/uso terapêutico , Neoplasias Retais/irrigação sanguínea , Estudos Retrospectivos , Programa de SEER , Inibidores de Simportadores de Cloreto de Sódio , Microambiente Tumoral/imunologia , Estados Unidos
8.
J Surg Res ; 266: 125-141, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33991999

RESUMO

OBJECTIVE: Valproic acid (VPA) treatment improves survival in animal models of injuries on doses higher than those allowed by Food and Drug Administration (FDA). We investigated the proteomic alterations induced by a single high-dose (140mg/kg) of VPA (VPA140) compared to the FDA-approved dose of 30mg/kg (VPA30) in healthy humans. We also describe the proteomic and transcriptomic changes induced by VPA140 in an injured patient. We hypothesized that VPA140 would induce cytoprotective changes in the study participants. METHODS: Serum samples were obtained from healthy subjects randomized to two groups; VPA140 and VPA30 at 3 timepoints: 0h(baseline), 2h, and 24h following infusion(n = 3/group). Samples were also obtained from an injured patient that received VPA140 at 0h, 6h and 24h following infusion. Proteomic analyses were performed using liquid chromatography-mass spectrometry (LC-MS/MS), and transcriptomic analysis was performed using RNA-sequencing. Differentially expressed (DE) proteins and genes were identified for functional annotation and pathway analysis using iPathwayGuide and gene set enrichment analysis (GSEA), respectively. RESULTS: For healthy individuals, a dose comparison was performed between VPA140 and VPA30 groups at 2 and 24 h. Functional annotation showed that top biological processes in VPA140 versus VPA30 analysis at 2 h included regulation of fatty acid (P = 0.002) and ATP biosynthesis (P = 0.007), response to hypoxia (P = 0.017), cell polarity regulation (P = 0.031), and sequestration of calcium ions (P = 0.031). Top processes at 24 h in VPA140 versus VPA30 analysis included amino acid metabolism (P = 0.023), collagen catabolism (P = 0.023), and regulation of protein breakdown (P = 0.023). In the injured patient, annotation of the DE proteins in the serum showed that top biological processes at 2 h included neutrophil chemotaxis (P = 0.002), regulation of cellular response to heat (P = 0.008), regulation of oxidative stress (P = 0.008) and regulation of apoptotic signaling pathway (P = 0.008). Top biological processes in the injured patient at 24 h included autophagy (P = 0.01), glycolysis (P = 0.01), regulation of apoptosis (P = 0.01) and neuron apoptotic processes (P = 0.02). CONCLUSIONS: VPA140 induces cytoprotective changes in human proteome not observed in VPA30. These changes may be responsible for its protective effects in response to injuries.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Substâncias Protetoras/farmacologia , Proteoma/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Ácido Valproico/farmacologia , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Cromatografia Líquida , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Perfilação da Expressão Gênica/métodos , Voluntários Saudáveis , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Substâncias Protetoras/uso terapêutico , Proteoma/metabolismo , Proteômica/métodos , Fatores de Tempo , Resultado do Tratamento , Ácido Valproico/uso terapêutico , Adulto Jovem
9.
Oxid Med Cell Longev ; 2021: 3165159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33747344

RESUMO

Phytocompounds and medicinal herbs were used in traditional ancient medicine and are nowadays increasingly screened in both experimental and clinical settings due to their beneficial effects in several major pathologies. Similar to the drug industry, phytotherapy is interested in using nanobased delivery systems to view the identification and characterization of the cellular and molecular therapeutic targets of plant components. Eugenol, the major phenolic constituent of clove essential oil, is a particularly versatile phytochemical with a vast range of therapeutic properties, among which the anti-inflammatory, antioxidant, and anticarcinogenic effects have been systematically addressed. In the past decade, with the emerging understanding of the role of mitochondria as critical organelles in the pathophysiology of noncommunicable diseases, research regarding the role of phytochemicals as modulators of bioenergetics and metabolism is on a rise. Here, we present a brief overview of the major pharmacological properties of eugenol, with special emphasis on its applications in dental medicine, and provide preliminary data regarding its effects, alone, and included in polyurethane nanostructures, on mitochondrial bioenergetics, and glycolysis in human HaCaT keratinocytes.


Assuntos
Eugenol/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Odontologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Substâncias Protetoras/farmacologia
10.
Life Sci ; 273: 119235, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33607152

RESUMO

Although the central role of Nurr-1/GDNF has been reviewed amply, scarce data are available on their peripheral impact. Carvedilol and morin hydrate have previously conferred their hepatic anti-fibrotic action. AIM: Thus, our aim was to unveil the potential hepatoprotective role of carvedilol (CR) and/or morin hydrate (MH) using a hepatic 70% partial warm ischemia/reperfusion (I/R) rat model. MAIN METHOD: Rats were allocated into sham-operated, hepatic I/R, and I/R preceded by oral administration of CR (10 and 30 mg/kg; CR10/CR30), MH (30 mg/kg), or CR10 + MH for one week. KEY FINDINGS: On the molecular level, pretreatment with CR and/or MH increased the hepatic contents of Nurr-1, GDNF, and the protein expression of active/p-AKT. On the other hand, they inactivated GSK3ß and NF-κB to increase the antioxidant enzymes (GPx, SOD, CAT). All regimens also enhanced the autophagy/lysosomal function and boosted the protein expression of beclin-1, LC3II, and TFEB. Moreover, their antiapoptotic effect was signified by increasing the anti-apoptotic molecule Bcl2 and inhibiting Bax, Bax/Bcl2 ratio, and caspase-3, effects that were confirmed by the TUNEL assay. These improvements were reflected on liver function, as they decreased serum aminotransferases and liver structural alterations induced by I/R. Despite its mild impact, CR10 showed marked improvements when combined with MH; this synergistic interaction overrides the effect of either regimen alone. SIGNIFICANCE: In conclusion, CR, MH, and especially the combination regimen, conferred hepatoprotection against I/R via activating the Nurr-1/GDNF/AKT trajectory to induce autophagy/lysosomal biogenesis, inhibit GSK3ß/NF-кB hub and apoptosis, and amend redox balance.


Assuntos
Carvedilol/farmacologia , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Isquemia/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Apoptose , Autofagia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Isquemia/metabolismo , Isquemia/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
11.
Int J Biol Macromol ; 171: 398-413, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33422516

RESUMO

Diatoms are ubiquitous, biologically widespread, and have global significance due to their unique silica cell wall composition and noteworthy applied aspects. Diatoms are being extensively exploited for environmental monitoring, reconstruction, and stratigraphic correlation. However, considering all the rich elements of diatoms biology, the current literature lacks sufficient information on the therapeutic attributes and applied aspects of biological macromolecules from diatoms, hampering added advances in all aspects of diatom biology. Diatoms offer numerous high-value compounds, such as fatty acids, polysaccharides, polypeptides, pigments, and polyphenols. Diatoms with a high content of PUFA's are targets of transformation into high-value products through microalgal technologies due to their wide application and growing market as nutraceuticals and food supplements. Diatoms are renewable biomaterial, which can be used to develop drug delivery systems due to biocompatibility, surface area, cost-effective ratio, and ease in surface modifications. Innovative approaches are needed to envisage cost-effective ways for the isolation of bioactive compounds, enhance productivity, and elucidate the detailed mechanism of action. This review spotlights the notable applications of diatoms and their biologically active constituents, such as fucoxanthin and omega 3 fatty acids, among others with unique structural and functional entities.


Assuntos
Diatomáceas/química , Substâncias Macromoleculares/uso terapêutico , Suplementos Nutricionais , Sistemas de Liberação de Medicamentos , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/uso terapêutico , Humanos , Substâncias Macromoleculares/economia , Substâncias Macromoleculares/isolamento & purificação , Peptídeos/isolamento & purificação , Peptídeos/uso terapêutico , Polifenóis/isolamento & purificação , Polifenóis/uso terapêutico , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Esteróis/isolamento & purificação , Esteróis/uso terapêutico , Xantofilas/isolamento & purificação , Xantofilas/uso terapêutico
12.
Chem Biol Drug Des ; 97(2): 341-348, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32931135

RESUMO

Picrorhiza kurroa has a long medicinal history as a traditional medicinal plant in China and India that is widely used in clinical treatments. It is a common treatment for liver diseases, fever, diarrhoea, indigestion, and some other diseases. Modern pharmacological studies proved that P. kurroa rhizomes have high levels of picroside I and II, which were identified as main constituents with anti-inflammatory and hepatoprotective activities. In our study, we used picroside I and II as the lead compounds to generate derivatives by reactions with Boc-valine or Boc-proline, which underwent dehydration and condensation with the hydroxyl groups in the lead compounds in the presence of coupling reagent N,N'-dicyclohexylcarbodiimide. We synthesized 11 derivatives and examined their hepatoprotective effects in vitro by assessing the proliferation rates of H2 O2 -exposed HepG2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. We found that some derivatives promoted higher proliferation rates in HepG2 cells than the natural compounds before derivatization, suggesting that those derivatives possessed an improved hepatoprotective capacity. The novel derivatization strategy for picrosides had the additional benefit that the esterification of their hydroxyl groups created derivatives not only with increased stability but also with improved pharmacokinetic properties and potentially prolonged half-life.


Assuntos
Aminoácidos/química , Cinamatos/química , Glucosídeos Iridoides/química , Substâncias Protetoras/química , Proliferação de Células/efeitos dos fármacos , Cinamatos/isolamento & purificação , Cinamatos/farmacologia , Células Hep G2 , Humanos , Peróxido de Hidrogênio/farmacologia , Glucosídeos Iridoides/isolamento & purificação , Glucosídeos Iridoides/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Picrorhiza/química , Picrorhiza/metabolismo , Plantas Medicinais/química , Plantas Medicinais/metabolismo , Substâncias Protetoras/farmacologia
13.
Toxicol In Vitro ; 67: 104921, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32599260

RESUMO

Silibinin (Sil) is used as hepatoprotective drug and is approved for therapeutic use in amanitin poisoning. In our study we compared Sil-bis-succinate (SilBS), a water-soluble drug approved for i.v.-administration, with Sil solved in ethanol (SilEtOH), which is normally used in research. We challenged monocultures or 3D-microtissues consisting of HepG2 cells or primary hepatocytes with α-amanitin and treated with SILBS, SILEtOH, penicillin and combinations thereof. Cell viability and the integrity of the microtissues was monitored. Finally, the expression of the transporters OATP1B1 and B3 was analyzed by qRT-PCR. We demonstrated that primary hepatocytes were more sensitive to α-amanitin compared to HepG2. Primary hepatocytes cultures were protected by SilBS and SilEtOH independent of penicillin from the cytotoxic effects of α-amanitin. Subsequent studies of the expression profile of the transporters OATP1B1/B3 revealed that primary hepatocytes do express both whereas in HepG2 cells they were hardly detectable. Our study showed that SilBS has significant advantage over SilEtOH with no additional benefit of penicillin. Moreover, HepG2 cells may not represent an appropriate model to investigate Amanita phalloides poisoning in vitro with focus on OATP transporters since these cells are lacking sensitivity towards α-amanitin probably due to missing cytotoxicity-associated transporters suggesting that primary hepatocytes should be preferred in this context.


Assuntos
Alfa-Amanitina/toxicidade , Penicilinas/farmacologia , Substâncias Protetoras/farmacologia , Silibina/farmacologia , Alternativas aos Testes com Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Modelos Biológicos , Substâncias Protetoras/química , Silibina/química , Esferoides Celulares
14.
Sci Total Environ ; 694: 133716, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756789

RESUMO

This study aims to quantify the selenium contribution from tuna to the Spanish diet and evidence the Se protective role against mercury and inorganic arsenic toxicity. Selenium concentrations in tuna were determined by ICP-MS spectrometry (expressed as mg kg-1), and the risk assessment was evaluated joined to Hg and iAs contrasting criteria of regulatory agencies with those that consider the Se protective role. Differences between Se average concentrations in fresh (1.24) and preserved (1.17) tuna were not statistically significant. In canned tuna species, Se presented higher mean levels in Thunnus albacares (1.28) than Thunnus alalunga (1.01) with statistically significant differences (p = 0.002), and among canned preparations a decreasing sequence was observed in different preparation-packaging media: oil (1.42) > natural (1.01) > pickled (0.92). Statistical study showed Hg-iAs as the only pair significantly correlated in all samples. The HI (sum of individual target hazard quotients -THQs-) on the consumption of tuna in Spain, due to exposure to Se, Hg and iAs, revealed the possibility of risk of adverse chronic effects in the six-year-old children group (1.09). According to the maximum allowable tuna consumption rate in meals/week (CRmw) and the THQs obtained, tuna intake, especially in children, should be moderated. The health benefit values (HBVSe) were positive in all samples, 14.53 and 15.65 in fresh and preserved tuna, respectively, which allows tuna to be considered safe. The benefit-risk value (BRV) evidenced the Se molar excess with respect to Hg that reached a surplus of 14.32% on Se AI in adults. Since iAs reduces the Se bioavailability, applying a new BRV criterion, the aforementioned percentage decreased to 13.49% of Se AI. In conclusion, tuna offers high levels of selenium to counteract adverse effects by the presence of Hg and iAs, and to provide consumers an important source of this essential element safely.


Assuntos
Arsênio/análise , Exposição Dietética/estatística & dados numéricos , Mercúrio/análise , Substâncias Protetoras/análise , Selênio/análise , Atum , Adulto , Animais , Criança , Contaminação de Alimentos , Humanos , Medição de Risco
15.
Environ Sci Pollut Res Int ; 26(32): 33304-33310, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520384

RESUMO

In this study, we present experimental data on the effects of meso-2,3-dimercaptosuccinic acid (DMSA) and tetraethylammonium salt of salinomycinic acid (Sal) on cadmium-induced spleen dysfunction and altered essential metal balance in mice. Sixty-day-old male mice (ICR line) were randomly divided into four groups: untreated control group (Ctrl)-obtained distilled water for 28 days, toxic control group (Cd)-exposed to cadmium acetate dihydrate at average daily dose of 20mg/kg body weight (BW) for 14 days, Cd + DMSA group-obtained cadmium acetate dihydrate as the toxic control group followed by treatment with 20mg/kg BW DMSA for 2 weeks, and Cd + Sal group-mice exposed to cadmium acetate dihydrate at average daily dose of 20mg/kg BW for 2 weeks followed by administration of Sal at an average daily dose of 20mg/kg BW for 2 weeks. The compounds were administered orally via the drinking water of the animals. We found that cadmium exposure caused splenomegaly and reduced the hemoglobin and hematocrit levels and total red blood cell count compared with untreated controls. Cadmium intoxication of mice induced accumulation of the toxic metal ion in the blood and spleen. Alterations in the endogenous levels of calcium (Ca) and iron (Fe) in the spleen of cadmium-exposed mice compared with those in untreated controls were observed. Treatment of cadmium-exposed mice with DMSA or Sal recovered the spleen weight and hematological parameters to normal control values, decreased cadmium concentration in the blood and spleen, and improved splenic architecture. The results prove that Sal is a potential antidote for treatment of Cd-induced spleen dysfunction.


Assuntos
Substâncias Protetoras/farmacologia , Piranos/farmacologia , Baço/efeitos dos fármacos , Succímero/farmacologia , Poluentes Químicos da Água/toxicidade , Acetatos , Animais , Cádmio/toxicidade , Cálcio , Água Potável , Ferro , Masculino , Camundongos , Camundongos Endogâmicos ICR , Baço/fisiologia
16.
Biotechniques ; 67(3): 98-109, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31347927

RESUMO

Poloxamers are water-soluble polymers that are widely used in cell culture bioprocessing to protect cells against shearing forces. Use of poor-quality poloxamers may lead to a drastic reduction in cell growth, viabilities and productivities in cell culture-based manufacturing. In order to evaluate poloxamer quality and promote more consistent performance, a rapid cell membrane adhesion to hydrocarbon assay was developed based on the adhesive properties of cell membranes to selective hydrocarbons. The assay can identify a poor-performing poloxamer characterized by significant drop in viable cell density and percent viability. The assay was verified across multiple good and bad poloxamer lots, and the results were in agreement with established cell growth and high-performance liquid chromatography assays.


Assuntos
Técnicas de Cultura de Células/métodos , Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Poloxâmero/farmacologia , Substâncias Protetoras/farmacologia , Animais , Células CHO , Contagem de Células/métodos , Técnicas de Cultura de Células/economia , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Cricetulus , Células HEK293 , Humanos , Poloxâmero/análise , Substâncias Protetoras/análise , Fatores de Tempo
17.
Am J Hum Biol ; 31(5): e23281, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31225943

RESUMO

OBJECTIVES: Tobacco and areca nut are two of the most widely used psychoactive plant substances worldwide, yet the biocultural factors that account for variation in use patterns are not well understood. Here we attempt to understand the high prevalence of, and variation in, tobacco and areca nut use among reproductive-aged women. METHODS: Research was carried out in Mysore, Karnataka, India. First, we conducted a qualitative investigation where participants engaged in semistructured interviews and focus group discussions to uncover cultural norms of women's tobacco use. Findings informed the second stage of research which quantitatively tested three models of tobacco and areca nut use (N = 74). RESULTS: The qualitative study found that women were more likely to chew "natural" forms of tobacco and areca nut products (kaddipudi and paan). Quantitative tests of our hypotheses revealed that kaddipudi and combined tobacco use were best explained by the self-medication model, with somatic and environmental stress as strong indicators of use. The presence of cotinine, our biological indicator of tobacco use, was best modeled by gender inequality. We also found that men and women reported approximately equal tobacco use, even though their preferred types of tobacco and areca nut products differed. CONCLUSIONS: Findings did not support the protection hypothesis as it relates to plant toxins. Instead, this study suggests that women might exploit neurotoxins such as nicotine and arecoline to offset the cognitive and energetic costs associated with iron deficiency in stressful environments.


Assuntos
Areca , Nozes , Substâncias Protetoras/uso terapêutico , Automedicação/estatística & dados numéricos , Fatores Socioeconômicos , Uso de Tabaco/epidemiologia , Tabaco sem Fumaça/estatística & dados numéricos , Adulto , Feminino , Humanos , Índia , Adulto Jovem
18.
Int J Mol Sci ; 20(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126043

RESUMO

Phytochemicals are known to benefit human health by modulating various cellular processes, including cell proliferation, apoptosis, and inflammation. Due to the potential use of phytochemicals as therapeutic agents against human diseases such as cancer, studies are ongoing to elucidate the molecular mechanisms by which phytochemicals affect cellular functions. It has recently been shown that phytochemicals may regulate the expression of microRNAs (miRNAs). MiRNAs are responsible for the fine-tuning of gene expression by controlling the expression of their target mRNAs in both normal and pathological cells. This review summarizes the recent findings regarding phytochemicals that modulate miRNA expression and promote human health by exerting anticancer, photoprotective, and anti-hepatosteatosis effects. Identifying miRNAs modulated by phytochemicals and understanding the regulatory mechanisms mediated by their target mRNAs will facilitate the efforts to maximize the therapeutic benefits of phytochemicals.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Fígado Gorduroso/tratamento farmacológico , MicroRNAs/genética , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Fígado Gorduroso/genética , Fígado Gorduroso/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Promoção da Saúde , Humanos , Neoplasias/genética , Neoplasias/prevenção & controle , Compostos Fitoquímicos/farmacologia , Substâncias Protetoras/farmacologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-30917103

RESUMO

Background Polychlorinated biphenyls (PCBs) are persistent organic chemicals that exert neurotoxic and endocrine disrupting effects. The aims of this study were to examine the effects of prenatal Aroclor 1254 (PCBs mixture) exposure on central nervous system tissues DNA and to evaluate the effects of curcumin. Methods Rat pups were assigned to three groups: [Group 1], Aroclor 1254 administrated group; [Group 2], Aroclor 1254 and curcumin administrated group; and [Group 3], control group. Plasma, cerebrum, cerebellum, pons and medulla oblongata tissue homogenates 8-hydroxy-2'-deoxyguanosine [8-(OH)DG] levels and plasma freeT4 levels were determined. Global DNA methylation and hydroxymethylation status were determined in cerebrum, cerebellum, pons and medulla oblongata. To this aim, DNA 5-hydroxymethylcytosine and 5-methylcytosine levels were measured, respectively. Results Mean cerebellum and cerebral cortex 5-hydroxymethylcytosine and 5-methylcytosine levels were higher in the control group than in the experimental groups. Mean plasma, cerebellum and cerebral cortex 8-(OH)DG concentrations were higher in Group 1 than the control group. No statistically significant difference was observed between Group 2 and the control group in terms of cerebellum and cerebral cortex 8-(OH)DG concentrations. Histopathological changes were also observed in the cerebral cortex and cerebellum of rat pups exposed to Aroclor 1254. PCBs exposure changes both DNA methylation and hypomethylation status and induces cerebellar and cerebral cortex DNA damage in the prenatal period. Exogenous curcumin may have protective effect on PCBs-induced DNA damage in cerebellum and cerebral cortex.


Assuntos
Curcumina/farmacologia , Dano ao DNA , Poluentes Ambientais/toxicidade , Epigênese Genética/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Substâncias Protetoras/farmacologia , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Encéfalo/patologia , Curcumina/administração & dosagem , Dano ao DNA/efeitos dos fármacos , Feminino , Masculino , Exposição Materna/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Substâncias Protetoras/administração & dosagem , Ratos , Ratos Wistar
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