Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 494
Filtrar
1.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638796

RESUMO

Diosmin, a natural flavone glycoside acquired through dehydrogenation of the analogous flavanone glycoside hesperidin, is plentiful in many citrus fruits. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor; the average survival time of GBM patients is less than 18 months after standard treatment. The present study demonstrated that diosmin, which is able to cross the blood-brain barrier, inhibited GBM cell growth in vitro and in vivo. Diosmin also impeded migration and invasion by GBM8401and LN229 GBM cells by suppressing epithelial-mesenchymal transition, as indicated by increased expression of E-cadherin and decreased expression of Snail and Twist. Diosmin also suppressed autophagic flux, as indicated by increased expression of LC3-II and p62, and induced cell cycle arrest at G1 phase. Importantly, diosmin did not exert serious cytotoxic effects toward control SVG-p12 astrocytes, though it did reduce astrocyte viability at high concentrations. These findings provide potentially helpful support to the development of new therapies for the treatment of GBM.


Assuntos
Autofagia/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Diosmina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Neoplasias Encefálicas/fisiopatologia , Linhagem Celular Tumoral , Diosmina/uso terapêutico , Feminino , Glioblastoma/fisiopatologia , Humanos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Urologiia ; (4): 53-60, 2021 09.
Artigo em Russo | MEDLINE | ID: mdl-34486275

RESUMO

INTRODUCTION: Chronic prostatitis is the most common urological disease. The morphological outcome of chronic inflammation is sclerosis, leading to the loss of functional active tissue. Venous congestion of the small pelvis can act as a trigger factor in the development of prostate sclerosis. Venotonics in combination with antioxidants may be considered for organoprotection of the prostate in pelvic varicose veins. PURPOSE: to evaluate the protective effect of an antioxidant, venotonic and their combination on the process of formation of connective tissue in the prostate gland against the background of pelvic varicose veins in a chronic experiment. MATERIALS AND METHODS: The experiment was carried out on a proven model of chronic venous congestion of the small pelvis and was carried out on 64 sexually mature rabbits weighing 2.6-3.2 kg. 5 groups have been identified. In the first group (n=15), an assessment of the effect of isolated antioxidant (resveratrol) was carried out. In the second group (n=15), an assessment of the effect of isolated venotonic (diosmin) was studied. In the third group (n=15), the effect of a combination of an antioxidant (resveratrol) and venotonic (diosmin) was evaluated. An aqueous solution of the preparations was injected daily for 180 days. In the fourth group (n=15), changes in the prostate were assessed against the background of venous congestion without exposure. In the fifth group (n=4), animals performed to provide data on normal anatomy. The animals were taken out of the experiment at 30, 90, 180 days. Prostate tissue was collected for histological examination and morphometry. In prostate samples, the concentration of hydroxyproline, a marker of connective tissue development, was investigated. RESULTS: the isolated administration of resveratrol, as well as diosmin, does not sufficiently compensate for the changes in the hemodynamics of the small pelvis and the toxic effect of metabolic products. With morphometry on day 180, the proportion of glandular tissue in the gland / fibrosis ratio was significantly higher, and fibrosis was lower in Group 3 (79.36 / 9.08 (p<0.01) than in Group 1 (63.1 / 22.74) and Group 2 (65.52 / 21.0) .Quantitative study of hydroxyproline showed lower concentrations in the samples of Group 3 18.44 mg% (p<0.01), relative to Groups 1 and 2 (39.7 and 34.44 mg%) There were no statistically significant differences in the studied parameters between Groups 1 and 2. CONCLUSION: the use of a combination of diosmin and resveratrol against the background of chronic venous hyperemia allowed, in the course of the presented experiment, to reduce the lesion volume and the growth of fibrous tissue in the prostate gland. The approach itself requires further study.


Assuntos
Diosmina , Prostatite , Varizes , Animais , Humanos , Masculino , Pelve , Coelhos , Varizes/tratamento farmacológico
3.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298934

RESUMO

In this paper, the electrochemical behavior of two types of sensors based on modified screen-printed electrodes (one screen-printed electrode based on carbon (SPCE) and another screen-printed electrode modified with Prussian Blue (PB/SPCE)) was studied with the aim of sensitive detection of diosmin, an active pharmaceutical compound from the class of flavonoids. The scan electron microscopy technique was used for the morphological characterization of PB/SPCE. The preliminary analysis assessed the electrochemical behavior of SPCE and PB/SPCE in KCl solution and in a double solution of potassium ferrocyanide-potassium chloride. It was shown that the active area of PB/SPCE is superior to the one of SPCE, the greater sensitivity being related with the presence of the electroactive modifier. Similarly, in the case of diosmin detection, the PB/SPCE sensor detect more sensitivity the diosmin due to the electrocatalytic effect of PB. From the study of the influence of reaction rate on the sensor's electrochemical response, it was shown that the detection process is controlled by the adsorption process, the degree of surface coverage with electroactive molecules being higher in the case of PB/SPCE. From the PB/SPCE calibration curve, it wasdetermined that it has high sensitivity and low detection and quantification limit values (limit of detection 5.22 × 10-8 M). The applicability of the PB/SPCE sensor was confirmed by sensitive analysis of diosmin in pharmaceutical products. The voltammetric method is suitable for the detection and quantification of diosmin in pharmaceutical products. The method is simple, accurate, and quick and can be used in routine analysis in the examination of the quality of pharmaceutical products and other types of samples.


Assuntos
Diosmina/química , Preparações Farmacêuticas/química , Carbono/química , Técnicas Eletroquímicas/métodos , Eletrodos , Limite de Detecção , Sensibilidade e Especificidade
4.
Int Angiol ; 40(5): 388-394, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34282857

RESUMO

BACKGROUND: The aim of this study was to characterize, in an experimental model, the mechanisms involved in the initiation of venous insufficiency at the level of microvenous valve and whether they can be influenced by early treatment with micronized purified flavonoid fraction (MPFF). METHODS: The external right iliac vein of 78 male golden Syrian hamsters was ligated to induce chronic venous insufficiency. Internal venular diameter as well as leukocyte-endothelium-interaction (leukocytes sticking after staining with rhodamine 6G), were assessed using an intravital microscope. In the second part of the study 30 animals were divided into three groups and underwent: ligation plus MPFF, ligation plus 10% lactose solution (vehicle), or sham operation. Treatment with MPFF 100 mg/kg/day or vehicle started 2 days before ligation and lasted for 7 days. Venular diameter and number of adherent leukocytes were assessed 5 days post-ligature. RESULTS: Venular diameter increased immediately after ligature and reached a maximum at 4 hours (P<0.001 vs. baseline), followed by a plateau before gradually returning to baseline dimensions. The increase in the number of adherent leukocytes was also immediate but attained maximal number at 3 days (P<0.0001), followed by a plateau and then gradual return to baseline numbers. In MPFF-treated animals, leukocyte adhesion to the microvalves was prevented compared with vehicle-treated animals (P<0.0001) and venular diameter was also significantly reduced (P<0.05). CONCLUSIONS: Venous hypertension induced immediate venular dilatation followed by an increase in the number of adherent leukocytes at microvalve level. Treatment with MPFF prevented the initiation of microvalve inflammation and may play a protective role in the progression of chronic venous insufficiency.


Assuntos
Diosmina , Hipertensão , Insuficiência Venosa , Animais , Cricetinae , Diosmina/farmacologia , Flavonoides , Veia Ilíaca , Masculino , Insuficiência Venosa/tratamento farmacológico
5.
Exp Parasitol ; 226-227: 108124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34139241

RESUMO

BACKGROUND: There is a necessity to develop or discover an alternative drug to combat the drug resistance by Giardia duodenalis and minimize the multiple doses and frequency of the conventional drug administration. Progressive repositioning or 'repurposing' of drugs has become widespread due to economic circumstances and medical emergency needs. Daflon 500 mg (DFL) is a natural product used safely as a nutrient supplement and an antidiabetic drug in many European countries and the US. OBJECTIVE: This study aimed at investigating the efficiency of DFL, in vivo, in a murine model as a safe alternative or co-drug for giardiasis. MATERIALS AND METHODS: Swiss Albino mice (n = 32) were inoculated with 1X104Giardia cysts and assigned to four groups: One group was the infected non-treated control mice and three experimental groups that were treated differently, either with Metronidazole (MTZ), DFL, or combined therapy of DFL/MTZ. Also, eight normal mice served as a control group. All mice were sacrificed 13 days post-infection for the parasitic, histopathological, and oxidative stress analysis. RESULTS: MTZ, DFL, and the combined therapy significantly reduced the number of trophozoites and cysts compared to their counterparts of the infected mice. The histopathological analysis of the small intestines of the mice treated with the combined therapy retained typical intestinal architecture and normal levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione. CONCLUSION: This study indicated promising actions of Daflon 500 as an anti-giardial drug, and the results demonstrated its potential effect in improving the intestinal epithelial tissue and disturbing the Giardia stages when it was taken collectively with Metronidazole.


Assuntos
Antiprotozoários/uso terapêutico , Diosmina/uso terapêutico , Giardíase/tratamento farmacológico , Metronidazol/uso terapêutico , Animais , Antiprotozoários/farmacologia , Diosmina/farmacologia , Combinação de Medicamentos , Fezes/parasitologia , Humanos , Intestinos/parasitologia , Intestinos/patologia , Metronidazol/farmacologia , Camundongos , Trofozoítos/efeitos dos fármacos
6.
Proteins ; 89(11): 1425-1441, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34169568

RESUMO

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still has serious negative effects on health, social life, and economics. Recently, vaccines from various companies have been urgently approved to control SARS-CoV-2 infections. However, any specific antiviral drug has not been confirmed so far for regular treatment. An important target is the main protease (Mpro ), which plays a major role in replication of the virus. In this study, Gaussian and residue network models are employed to reveal two distinct potential allosteric sites on Mpro that can be evaluated as drug targets besides the active site. Then, Food and Drug Administration (FDA)-approved drugs are docked to three distinct sites with flexible docking using AutoDock Vina to identify potential drug candidates. Fourteen best molecule hits for the active site of Mpro are determined. Six of these also exhibit high docking scores for the potential allosteric regions. Full-atom molecular dynamics simulations with MM-GBSA method indicate that compounds docked to active and potential allosteric sites form stable interactions with high binding free energy (∆Gbind ) values. ∆Gbind values reach -52.06 kcal/mol for the active site, -51.08 kcal/mol for the potential allosteric site 1, and - 42.93 kcal/mol for the potential allosteric site 2. Energy decomposition calculations per residue elucidate key binding residues stabilizing the ligands that can further serve to design pharmacophores. This systematic and efficient computational analysis successfully determines ivermectine, diosmin, and selinexor currently subjected to clinical trials, and further proposes bromocriptine, elbasvir as Mpro inhibitor candidates to be evaluated against SARS-CoV-2 infections.


Assuntos
Antivirais/metabolismo , Benzofuranos/química , Proteases 3C de Coronavírus/metabolismo , Reposicionamento de Medicamentos/métodos , Imidazóis/química , Sítio Alostérico , Antivirais/química , Antivirais/farmacologia , Benzofuranos/metabolismo , Benzofuranos/farmacologia , Sítios de Ligação , Bromocriptina/química , Bromocriptina/metabolismo , Bromocriptina/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/química , Diosmina/química , Diosmina/metabolismo , Hidrazinas/química , Hidrazinas/metabolismo , Hidrazinas/farmacologia , Imidazóis/metabolismo , Imidazóis/farmacologia , Ivermectina/química , Ivermectina/metabolismo , Ivermectina/farmacologia , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Triazóis/química , Triazóis/metabolismo , Triazóis/farmacologia , Estados Unidos , United States Food and Drug Administration
7.
J Oleo Sci ; 70(5): 665-673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33952791

RESUMO

Cancer is the world's biggest health problem and cancer-induced mortality happened all over the planet after the heart disease. The present study was to scrutinize the anti-leukemia effect of diosmin against Dalton Ascitic Lymphoma (DAL) induced leukemia in mice. DAL cell was used for induction the solid tumor. Body weight, life spans, tumor volume and mean survival time was estimated. Antioxidant, biochemical and pro-inflammatory cytokines were estimated. Diosmin showed the cell viability effect at dose dependent manner against the both cell lines. DAL induced solid tumor mice showed the decreased body weight, mean survival days, non viable cell count and increased the tumor volume, viable cell count and diosmin significantly (p < 0.001) reverse the effect of DAL. Diosmin significantly (p < 0.001) altered the hematological, differential leukocytes, antioxidant, biochemical, pro-inflammatory cytokines at dose dependently. Collectively, we can say that diosmin might alter the DAL induced abnormality via antioxidant and anti-inflammatory effects.


Assuntos
Anti-Inflamatórios , Antineoplásicos Fitogênicos , Ascite/patologia , Sobrevivência Celular/efeitos dos fármacos , Diosmina/farmacologia , Leucemia/patologia , Linfoma/patologia , Animais , Antioxidantes , Células Cultivadas , Citrus/química , Citocinas/metabolismo , Diosmina/administração & dosagem , Diosmina/isolamento & purificação , Relação Dose-Resposta a Droga , Mediadores da Inflamação/metabolismo , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Linfoma/tratamento farmacológico , Linfoma/metabolismo , Camundongos Endogâmicos BALB C , Fitoterapia
8.
Nutrients ; 13(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808784

RESUMO

Chronic Venous Disease (CVD) is a common medical condition affecting up to 80% of the general population. Clinical manifestations can range from mild to more severe signs and symptoms that contribute to the impairment of the quality of life (QoL) of affected patients. Among treatment options, venoactive drugs such as diosmin are widely used in the symptomatic treatment in all clinical stages. The aim of this study is to determine the effectiveness of a new formulated diosmin in relieving symptoms and improving QoL in patients suffering from CVD. In this randomized, double-blind, placebo-controlled, multicenter clinical study, CVD patients with a Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification system between C2 and C4 were randomized to receive a bioavailable diosmin (as µsmin® Plus) 450 mg tablet once daily or a placebo for 8 weeks. Clinical symptoms and QoL were monitored using the measurement of leg circumference, visual analogue scale (VAS) for pain, Global Index Score (GIS) and Venous Clinical Severity Score (VCSS). A total of 72 subjects completed the study. From week 4, leg edema was significantly decreased in the active group (p < 0.001). An improvement in the VAS score was observed in the active group compared to placebo at the end of treatment (p < 0.05). GIS and VCSS scores were significantly improved in the active group at week 8 (p < 0.001). No treatment related-side effects were recorded. The results of this study showed that the administration of low-dose µsmin® Plus was safe and effective in relieving symptoms and improving QoL in subjects with CVD.


Assuntos
Doença Crônica/tratamento farmacológico , Diosmina/uso terapêutico , Qualidade de Vida , Doenças Vasculares/tratamento farmacológico , Adolescente , Adulto , Método Duplo-Cego , Edema , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Medição da Dor , Veias , Adulto Jovem
9.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802633

RESUMO

The current study was designed to investigate the protective role of diosmin against cyclophosphamide-induced premature ovarian insufficiency (POI). Female Swiss albino rats received a single intraperitoneal dose of cyclophosphamide (200 mg/kg) followed by 8 mg/kg/day for the next 15 consecutive days either alone or in combination with oral diosmin at 50 or 100 mg/kg. Histopathological examination of ovarian tissues, hormonal assays for follicle stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH), assessment of the oxidative stress status, as well as measurement of the relative expression of miRNA-145 and its target genes [vascular endothelial growth factor B (VEGF-B) and regulator of cell cycle (RGC32)] were performed. Diosmin treatment ameliorated the levels of E2, AMH, and oxidative stress markers. Additionally, both low and high diosmin doses significantly reduced the histopathological alterations and nearly preserved the normal ovarian reserve. MiRNA-145 expression was upregulated after treatment with diosmin high dose. miRNA-145 target genes were over-expressed after both low and high diosmin administration. Based on our findings, diosmin has a dose-dependent protective effect against cyclophosphamide-induced ovarian toxicity in rats.


Assuntos
Diosmina/uso terapêutico , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Caspase 3/metabolismo , Catalase/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Colágeno/metabolismo , Ciclofosfamida , Diosmina/farmacologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios/sangue , Malondialdeído/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/patologia , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Ovariana Primária/sangue , Insuficiência Ovariana Primária/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Life Sci ; 275: 119349, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33744325

RESUMO

AIM: Gentamicin (GM) is an aminoglycoside antibiotic effectively used for severe/life-threatening infections. However, the clinical application of GM is limited by nephrotoxic side effects. Diosmin (DS) is a flavonoid with a wide range of bioactivities. However, its therapeutic potential in GM-induced nephrotoxicity remains unclear. METHODS: Rats received GM (100 mg/kg, i.p.) for 7 days either separately or in combination with oral DS (50 mg/kg). RESULTS: GM injection disrupted kidney function along with oxidant/antioxidant imbalance. Also, GM significantly decreased renal nuclear factor erythroid 2-related factor 2 (Nrf2), glutamyl cysteine synthetase (GCLC), heme oxygenase-1 (HO-1), superoxide dismutase3 (SOD-3), protein kinase B (AKT), and p-AKT expressions along with Kelch-like ECH-associated protein 1 (KEAP1) up-regulation. On the contrary, DS administration significantly attenuated GM-induced kidney dysfunction and restored kidney oxidant/antioxidant status. In addition, co-treatment with DS plus GM significantly enhanced Nrf2, GCLC, HO-1, SOD3, AKT, and p-AKT expressions along with KEAP1 down-regulation. Additionally, GM-treated rats exhibited a significant decrease in the expressions of renal peroxisome-proliferator activated receptor-gamma (PPAR-γ) and this reduction was alleviated by DS treatment. Furthermore, histopathological findings demonstrated that DS significantly reduced the GM-induced histological abrasions. Besides, an in-silico study was conducted to confirm our biochemical results. Interestingly, in-silico results strongly supported our biochemical investigation by studying the binding affinity of DS to KEAP1, AKT, and PPAR-γ proteins. SIGNIFICANCE: DS could be a promising protective agent against GM-induced nephrotoxicity through targeting of KEAP1/Nrf2/ARE, AKT, and PPAR-γ signaling pathways.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Diosmina/uso terapêutico , Gentamicinas/toxicidade , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína Oncogênica v-akt/metabolismo , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Injúria Renal Aguda/patologia , Injúria Renal Aguda/prevenção & controle , Animais , Western Blotting , Creatinina/sangue , Diosmina/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Wistar , Ureia/sangue , Ácido Úrico/sangue
11.
Methods ; 195: 44-56, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33639316

RESUMO

Novel coronavirus SARS-CoV-2continues tospread rapidly worldwide and causing serious health and economic loss. In the absence of any effective treatment, various in-silico approaches are being explored towards the therapeutic discovery against COVID-19. Targeting multiple key enzymes of SARS-CoV-2 with a single potential drug could be an important in-silico strategy to tackle the therapeutic emergency. A number of Food and Drug Administration (FDA) approved drugs entered into clinical stages were originated from multi-target approaches with an increased rate, 16-21% between 2015 and 2017. In this study, we selected an FDA-approved library (Prestwick Chemical Library of 1520 compounds) and implemented in-silico virtual screening against multiple protein targets of SARS-CoV-2 on the Glide module of Schrödinger software (release 2020-1). Compounds were analyzed for their docking scores and the top-ranked against each targeted protein were further subjected to Molecular Dynamics (MD) simulations to assess the binding stability of ligand-protein complexes. A multi-targeting approach was optimized that enabled the analysis of several compounds' binding efficiency with more than one protein targets. It was demonstrated that Diosmin (6) showed the highest binding affinity towards multiple targets with binding free energy (kcal/mol) values of -63.39 (nsp3); -62.89 (nsp9); -31.23 (nsp12); and -65.58 (nsp15). Therefore, our results suggests that Diosmin (6) possesses multi-targeting capability, a potent inhibitor of various non-structural proteins of SARS-CoV-2, and thus it deserves further validation experiments before using as a therapeutic against COVID-19 disease.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Diosmina/farmacologia , Antivirais/uso terapêutico , COVID-19/virologia , Proteases Semelhantes à Papaína de Coronavírus/antagonistas & inibidores , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , RNA-Polimerase RNA-Dependente de Coronavírus/antagonistas & inibidores , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Diosmina/uso terapêutico , Descoberta de Drogas , Endorribonucleases/antagonistas & inibidores , Endorribonucleases/metabolismo , Humanos , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas de Ligação a RNA , SARS-CoV-2/metabolismo , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/metabolismo
12.
Environ Sci Pollut Res Int ; 28(13): 15890-15908, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33242198

RESUMO

The aim of this study was to investigate the protective efficacy of diosmin against subacute deltamethrin exposure. For this purpose, 40 male Wistar albino rats were used. The animals were assigned to the following 4 groups: control group (received corn oil vehicle alone), diosmin-treated group (50 mg/kg bw/day orally), deltamethrin-exposed group (5 mg/kg bw/day, orally) and coadministered group (5 mg/kg bw/day deltamethrin and 50 mg/kg bw/day diosmin, orally) for 28 days. Some lipid peroxidation/antioxidant status/biochemical markers were evaluated in blood/tissue (liver, kidney, brain, heart and testis) samples and the histopathological architecture was assessed. Compared with the control group, no alteration was detected in the parameters and histological findings of the diosmin-treated group. Deltamethrin toxicity was associated with significantly increased plasma, cardiac, hepatic, renal, cerebral and testicular levels of MDA and NO, and significantly decreased GSH levels (p < 0.05). Antioxidant enzyme status (SOD, CAT and GSH-Px activities) displayed either decrease or increase (p < 0.05). Significant increase was detected in AST and ALT activities and urea and creatinine levels (p < 0.05). The values of the group coadministered with deltamethrin and diosmin were similar to the values of the control group. Diosmin ameliorated deltamethrin-induced lymphocytic and histiocytic infiltration and subendocardial oedema in the heart. Combined administration also minimized hepatic, renal, testicular and cerebral histopathological findings. The alterations detected in various toxicological parameters correlated well with the histopathological changes observed in various organs. In conclusion, it is suggested that diosmin could provide protection against deltamethrin-induced toxicity and organ damage in rats.


Assuntos
Diosmina , Animais , Antioxidantes/metabolismo , Rim , Peroxidação de Lipídeos , Lipídeos , Fígado/metabolismo , Masculino , Nitrilas , Estresse Oxidativo , Piretrinas , Ratos , Ratos Wistar
13.
Phytomedicine ; 81: 153418, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33302042

RESUMO

BACKGROUND: Atopic dermatitis (AD) is an inflammatory chronic skin disease that is characterized by the dysfunction or lack of skin barrier proteins. Recent studies have proposed that the pharmacological upregulation of skin barrier proteins is an effective treatment for AD. Aryl hydrocarbon receptor (AhR) is a transcription factor that positively regulates the expression of skin barrier proteins upon its activation. PURPOSE: This study aimed to identify AhR agonists from phytochemicals and investigate its effect on skin barrier restoration as well as its mechanisms of action in AD. STUDY DESIGN: A publicly available assay database and HaCaT cells stably transduced with a luciferase gene driven by an AhR-target gene promoter (CYP1A1) were used to screen for the activity of AhR agonists from phytochemicals. Normal human epidermal keratinocytes (NHEKs) and a human skin equivalent (HSE) model were used to investigate the effect of AhR agonists on skin restoration and its underlying mechanisms. METHODS: A Gaussia luciferase assaywas performed to screen for AhR agonist activity. Western blotting, qRT-PCR analysis, immunofluorescence, drug affinity responsive target stability assay, and siRNA-mediated AhR knockdown were performed in NHEKs. Hematoxylin and eosin staining was performed to measure epidermal thickness in the HSE model. RESULTS: Diosmin, a potential AhR agonist derived from natural products, upregulated the expression of skin barrier proteins (filaggrin and loricrin) and their upstream regulator (OVOL1) in NHEKs. Diosmin treatment also increased epidermal thickness in the HSE model. In addition, incubating NHEKs with diosmin restored the expression of skin barrier proteins and mRNAs that were suppressed by Th2 cytokines and inhibited STAT3 phosphorylation that was induced by Th2 cytokines. Diosmin also upregulated the expression of NQO1, a negative regulator of STAT3. Immunofluorescence results showed that diosmin stimulated AhR nuclear translocation, and the drug affinity responsive target stability assay revealed that this phytochemical directly bound to AhR. Furthermore, AhR knockdown abolished diosmin-induced filaggrin and loricrin expression. CONCLUSION: These results suggest that diosmin is a potential treatment for AD that targets AhR.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/farmacologia , Diosmina/farmacologia , Receptores de Hidrocarboneto Arílico/metabolismo , Pele/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/agonistas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Linhagem Celular , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Proteínas de Ligação a DNA/metabolismo , Dermatite Atópica/patologia , Avaliação Pré-Clínica de Medicamentos/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Compostos Fitoquímicos/farmacologia , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/genética , Pele/metabolismo , Pele/patologia , Células Th2/metabolismo , Fatores de Transcrição/metabolismo , Regulação para Cima/efeitos dos fármacos
14.
Cochrane Database Syst Rev ; 11: CD003229, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141449

RESUMO

BACKGROUND: Chronic venous insufficiency (CVI) is a condition in which veins are unable to transport blood unidirectionally towards the heart. CVI usually occurs in the lower limbs. It might result in considerable discomfort, with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is the second update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered orally or topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and Clinicaltrials.gov trials register up to 12 November 2019. We searched the reference lists of the articles retrieved by electronic searches for additional citations. We also contacted authors of unpublished studies. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of phlebotonics (rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, French maritime pine bark extract, grape seed extract and aminaftone) in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence intervals (CIs) and percentage of heterogeneity (I2). Outcomes of interest were oedema, quality of life (QoL), assessment of CVI and adverse events. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: We identified three new studies for this update. In total, 69 RCTs of oral phlebotonics were included, but only 56 studies (7690 participants, mean age 50 years) provided quantifiable data for the efficacy analysis. These studies used different phlebotonics (28 on rutosides, 11 on hidrosmine and diosmine, 10 on calcium dobesilate, two on Centella asiatica, two on aminaftone, two on French maritime pine bark extract and one on grape seed extract). No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-certainty evidence suggests that phlebotonics probably reduce oedema slightly in the lower legs, compared with placebo (RR 0.70, 95% CI 0.63 to 0.78; 13 studies; 1245 participants); and probably reduce ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; 15 studies; 2010 participants). Moderate-certainty evidence shows that phlebotonics probably make little or no difference in QoL compared with placebo (SMD -0.06, 95% CI -0.22 to 0.10; five studies; 1639 participants); and similarly, may have little or no effect on ulcer healing (RR 0.94, 95% CI 0.79 to 1.13; six studies; 461 participants; low-certainty evidence). Thirty-seven studies reported on adverse events. Pooled data suggest that phlebotonics probably increase adverse events slightly, compared to placebo (RR 1.14, 95% CI 1.02 to 1.27; 37 studies; 5789 participants; moderate-certainty evidence). Gastrointestinal disorders were the most frequently reported adverse events. We downgraded our certainty in the evidence from 'high' to 'moderate' because of risk of bias concerns, and further to 'low' because of imprecision. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that phlebotonics probably reduce oedema slightly, compared to placebo; moderate-certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing. Moderate-certainty evidence suggests that phlebotonics are probably associated with a higher risk of adverse events than placebo. Studies included in this systematic review provided only short-term safety data; therefore, the medium- and long-term safety of phlebotonics could not be estimated. Findings for specific groups of phlebotonics are limited due to small study numbers and heterogeneous results. Additional high-quality RCTs focusing on clinically important outcomes are needed to improve the evidence base.


Assuntos
Fármacos Hematológicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Insuficiência Venosa/tratamento farmacológico , Ácido 4-Aminobenzoico/uso terapêutico , Angioedemas Hereditários/tratamento farmacológico , Dobesilato de Cálcio/uso terapêutico , Centella , Doença Crônica , Diosmina/análogos & derivados , Diosmina/uso terapêutico , Edema/tratamento farmacológico , Humanos , Perna (Membro) , Úlcera da Perna/tratamento farmacológico , Pessoa de Meia-Idade , Fitoterapia/métodos , Pinus , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Rutina/uso terapêutico , para-Aminobenzoatos/uso terapêutico
15.
Cienc. tecnol. salud ; 7(3): 412-441, 26 de noviembre 2020. ^c27 cmilus
Artigo em Espanhol | LILACS, LIGCSA, DIGIUSAC | ID: biblio-1141472

RESUMO

Las infecciones respiratorias constituyen una importante causa de morbilidad y mortalidad a nivel mundial, incrementándose su relevancia ante la reciente infección por SARS-CoV-2, causante de la pandemia de COVID-19. Las opciones terapéuticas para esta infección respiratoria son escasas y sin eficacia comprobada. El objetivo de esta revisión fue buscar la información sobre plantas con actividad antiviral o viricida publicada en los últimos 10 años, en las bases de datos de Google Scholar, Scopus y PubMed. La búsqueda priorizó aquellas especies disponibles en Guatemala, la cual se complementó con la búsqueda de moléculas con actividad antiviral para finalmente postular aquellas que puedan prevenir la infección o aminorar la patogénesis del SARS-CoV-2. Se detectaron más de 170 especies con actividad antiviral y se organizó la información por país o región y tipo de actividad antiviral contra virus específicos. De las especies de mayor disponibilidad en Guatemala se seleccionaron 20. La revisión culmina con 15 artículos que proponen plantas o moléculas con potencial actividad específica en el manejo de la pandemia por SARS-CoV-2. Se concluye que existen especies vegetales (Curcuma longa, Echinacea purpurea, Psidium guajava, Allium sativum, Salvia officinalis y Eucalyptus globulus) y fitocompuestos vegetales (hesperidina, rutina, diosmina, apiina, aloe-emodina, piperina, capsaicina, curcumina, oleuropeina, rhamnetina y gallato de epicatequina) que podrían contribuir al manejo de la enfermedad. Se insta a académicos y autoridades a poner más atención a estas opciones terapéuticas que nos ofrece la naturaleza y que podrían contribuir a aliviar el colapso de los sistemas de salud prevalentes.


Respiratory infections are an important cause of morbidity and mortality worldwide, increasing their relevance by the recent SARS-CoV-2 infection causing the COVID-19 pandemic. Therapeutic options for this respiratory infection are scarce and without proven effectiveness. The objective of this review was the search for information on plants with antiviral or viricidal activity published in the last 10 years in the Google Scholar, Scopus, and PubMed databases. The search prioritized those species available in Guatemala, was completed with the search of molecules with potential to prevent infection or reduce the activity of SARS-CoV-2 infection. More than 170 species with antiviral activity were detected and the information organized in surveys by country or region, activity against specific viruses and antiviral information on the 20 most commonly available species in the country. It is complemented with a summary of 15 articles that proposed plants or molecules with potential specific activity in the management of the SARS-CoV-2 pandemic. It is concluded there are plant species (Curcuma longa, Echinacea purpurea, Psidium guajava, Allium sativum, Salvia officinalis and Eucalyptus globulus) and phytocompounds isolated from these species (hesperidin, rutin, diosmin, apiine, aloe-emodin, piperine, capsaicin, curcumin, oleuropein and epicatechin gallate) that could contribute to the management of the disease. Academics and authorities are urged to pay more attention to these therapeutic options that nature offer to us and could contribute to alleviate the collapse of the prevailing health systems in the country.


Assuntos
Humanos , Plantas Medicinais/efeitos dos fármacos , Infecções Respiratórias , Terapêutica , Catequina/uso terapêutico , Echinacea , Curcumina/uso terapêutico , Salvia officinalis , Psidium , Diosmina , Aloe , Eucalyptus , Betacoronavirus , Alho , COVID-19 , Guatemala , Hesperidina
16.
J Phys Chem Lett ; 11(21): 9272-9281, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33085491

RESUMO

Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 1000000 deaths all over the world and still lacks a medical treatment despite the attention of the whole scientific community. Human angiotensin-converting enzyme 2 (ACE2) was recently recognized as the transmembrane protein that serves as the point of entry of SARS-CoV-2 into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the protein complex. Moreover, the free energy of binding between ACE2 and the active receptor binding domain of the SARS-CoV-2 spike protein is evaluated quantitatively, providing for the first time the thermodynamics of virus-receptor recognition. Furthermore, the action of different ACE2 ligands is also examined in particular in their capacity to disrupt SARS-CoV-2 recognition, also providing via a free energy profile the quantification of the ligand-induced decreased affinity. These results improve our knowledge on molecular grounds of the SARS-CoV-2 infection and allow us to suggest rationales that could be useful for the subsequent wise molecular design for the treatment of COVID-19 cases.


Assuntos
Betacoronavirus/metabolismo , Ligantes , Peptidil Dipeptidase A/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Enzima de Conversão de Angiotensina 2 , Sítios de Ligação , COVID-19 , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Diosmina/química , Diosmina/metabolismo , Humanos , Simulação de Dinâmica Molecular , Pandemias , Peptidil Dipeptidase A/química , Plicamicina/química , Plicamicina/metabolismo , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Ligação Proteica , Domínios Proteicos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química , Termodinâmica
17.
Vnitr Lek ; 66(2): 97-103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32942884

RESUMO

With the advent of novel monocomponent venoactive drugs containing the flavonoid diosmin, the need has arisen to answer the question of therapeutic equivalence of the widely used micronized purified flavonoid fraction (MPFF) contained in Detralex and of the currently introduced monocomponent venoactive drugs. Experimental work provides evidence that each of the two dominant components, i.e. diosmin and hesperidin, has its specific and distinctive pharmacodynamic effect. There is also evidence of a mutual synergistic effect, e.g. in antiexudative action. Clinical studies have been carried out with MPFF for the most part, and effect has clearly been established in this particular form. Conversely, the results of studies documenting the effect of diosmin alone have been conflicting. Mutual comparisons failed to confirm equivalence of MPFF and monocomponent diosmin in any of the studies. This fact is clearly reflected in the relevant guidelines where the use of MPFF in chronic venous disease is recommended unequivocally (level of evidence 1 and strength of evidence B) while, in the case of monocomponent diosmin, it is stated that treatment can be considered (2C). It can be concluded that both experimental and clinical studies document that only a complex of biologically active flavonoids - a micronized purified flavonoid fraction - has evidence of effect and is recommended by relevant guidelines.


Assuntos
Diosmina , Hesperidina , Doenças Vasculares , Doença Crônica , Diosmina/farmacologia , Flavonoides , Hesperidina/farmacologia , Humanos
18.
Food Funct ; 11(10): 8472-8492, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32966476

RESUMO

Diosmin is a famous natural flavonoid for treating chronic venous insufficiency and varicose veins. Recently, extensive study has indicated that diosmin possesses diverse pharmacological activities, including anti-inflammation, anti-oxidation, anti-diabetes, anti-cancer, anti-microorganism, liver protection, neuro-protection, cardiovascular protection, renoprotection, and retinal protection activities. Due to its low water solubility, diosmin is dramatically limited in clinical application. Expectedly, many potential strategies have been developed for improving its pharmacokinetic values and bioavailability. This health-benefiting compound has been explored as the major component of Daflon and micronized purified flavonoid fraction (MPFF), which have been used in clinics to improve micro-circulation. However, no specific drug targets for diosmin are reported, although some potential factors have been involved in screening, such as P-glycoprotein (P-gp), IKKß, acetylcholinesterase (AChE), and aldose reductase (AR). More investigations on the underlying mechanisms of diosmin in mediating cellular processes with high specificity is still needed.


Assuntos
Diosmina/metabolismo , Diosmina/farmacologia , Animais , Anti-Infecciosos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Fármacos Cardiovasculares/farmacologia , Diosmina/uso terapêutico , Humanos , Hipoglicemiantes/farmacologia , Nefropatias/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Doenças Retinianas/tratamento farmacológico
20.
Med Hypotheses ; 144: 109957, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32531538

RESUMO

SARS-CoV-2 or COVID-19 is representing the major global burden that implicated more than 4.7 million infected cases and 310 thousand deaths worldwide in less than 6 months. The prevalence of this pandemic disease is expected to rise every day. The challenge is to control its rapid spread meanwhile looking for a specific treatment to improve patient outcomes. Hesperidin is a classical herbal medicine used worldwide for a long time with an excellent safety profile. Hesperidin is a well-known herbal medication used as an antioxidant and anti-inflammatory agent. Available shreds of evidence support the promising use of hesperidin in prophylaxis and treatment of COVID 19. Herein, we discuss the possible prophylactic and treatment mechanisms of hesperidin based on previous and recent findings. Hesperidin can block coronavirus from entering host cells through ACE2 receptors which can prevent the infection. Anti-viral activity of hesperidin might constitute a treatment option for COVID-19 through improving host cellular immunity against infection and its good anti-inflammatory activity may help in controlling cytokine storm. Hesperidin mixture with diosmin co-administrated with heparin protect against venous thromboembolism which may prevent disease progression. Based on that, hesperidin might be used as a meaningful prophylactic agent and a promising adjuvant treatment option against SARS-CoV-2 infection.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/prevenção & controle , Hesperidina/uso terapêutico , Pandemias/prevenção & controle , Fitoterapia , SARS-CoV-2/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/efeitos dos fármacos , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , COVID-19/complicações , COVID-19/epidemiologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Diosmina/administração & dosagem , Diosmina/uso terapêutico , Quimioterapia Combinada , Heparina/administração & dosagem , Heparina/uso terapêutico , Hesperidina/administração & dosagem , Hesperidina/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Receptores Virais/efeitos dos fármacos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...