Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 504
Filtrar
1.
Molecules ; 26(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669054

RESUMO

Despite the virulence and high fatality of coronavirus disease 2019 (COVID-19), no specific antiviral treatment exists until the current moment. Natural agents with immune-promoting potentials such as bee products are being explored as possible treatments. Bee honey and propolis are rich in bioactive compounds that express strong antimicrobial, bactericidal, antiviral, anti-inflammatory, immunomodulatory, and antioxidant activities. This review examined the literature for the anti-COVID-19 effects of bee honey and propolis, with the aim of optimizing the use of these handy products as prophylactic or adjuvant treatments for people infected with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Molecular simulations show that flavonoids in propolis and honey (e.g., rutin, naringin, caffeic acid phenyl ester, luteolin, and artepillin C) may inhibit viral spike fusion in host cells, viral-host interactions that trigger the cytokine storm, and viral replication. Similar to the potent antiviral drug remdesivir, rutin, propolis ethanolic extract, and propolis liposomes inhibited non-structural proteins of SARS-CoV-2 in vitro, and these compounds along with naringin inhibited SARS-CoV-2 infection in Vero E6 cells. Propolis extracts delivered by nanocarriers exhibit better antiviral effects against SARS-CoV-2 than ethanolic extracts. In line, hospitalized COVID-19 patients receiving green Brazilian propolis or a combination of honey and Nigella sativa exhibited earlier viral clearance, symptom recovery, discharge from the hospital as well as less mortality than counterparts receiving standard care alone. Thus, the use of bee products as an adjuvant treatment for COVID-19 may produce beneficial effects. Implications for treatment outcomes and issues to be considered in future studies are discussed.


Assuntos
Antivirais , Mel , Simulação de Dinâmica Molecular , Própole , /metabolismo , Animais , Antivirais/química , Antivirais/uso terapêutico , /epidemiologia , Chlorocebus aethiops , Ensaios Clínicos como Assunto , Flavanonas/química , Flavanonas/uso terapêutico , Nigella sativa/química , Própole/química , Própole/uso terapêutico , Células Vero
2.
Int J Mol Sci ; 22(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669855

RESUMO

Colitis is a multifactorial disorder that mostly occurs in the gastrointestinal tract. Despite improvements in mucosal inflammation research, little is known regarding the small bioactive molecules that are beneficial for regulating T cells and colon cell activity. 6,7,4'-trihydroxyflavanone (THF) is a flavanone that possesses anti-osteoclastogenesis activity and exerts protective effects against methamphetamine-induced immunotoxicity. Whether THF mitigates intestinal inflammation by regulating T cells and colon cell activity remains unknown. In the present study, Jurkat and HT-29 cells were used for in vitro experiments, and dextran sulfate sodium (DSS)-induced colitis model in mice was used for in vivo experiment. We observed that THF did not have a negative effect on the viability of Jurkat and HT-29 cells. Quantitative PCR and Western blot analysis revealed that THF regulates the activity of Jurkat cells and HT-29 cells via the NFκB and MAPK pathways under stimulated conditions. In the DSS-induced colitis model, oral administration of THF attenuated the manifestations of DSS-induced colitis, including a reduction in body weight, shrinkage of the colon, and enhanced expression of pro-inflammatory cytokines in the colon and mesenteric lymph nodes. These data suggest that THF alleviates DSS-induced colitis by modulating the activity of T cells and colon cells in vivo.


Assuntos
Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/imunologia , Colo/patologia , Flavanonas/uso terapêutico , Substâncias Protetoras/uso terapêutico , Linfócitos T/imunologia , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colite/imunologia , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Feminino , Flavanonas/administração & dosagem , Flavanonas/química , Flavanonas/farmacologia , Células HT29 , Humanos , Inflamação/patologia , Intestinos/patologia , Células Jurkat , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Substâncias Protetoras/farmacologia , Linfócitos T/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Fator de Transcrição RelA/metabolismo
3.
Int J Mol Sci ; 22(2)2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33467209

RESUMO

Skeletal muscle is the most abundant tissue and constitutes about 40% of total body mass. Herein, we report that crude water extract (CWE) of G. uralensis enhanced myoblast proliferation and differentiation. Pretreatment of mice with the CWE of G. uralensis prior to cardiotoxin-induced muscle injury was found to enhance muscle regeneration by inducing myogenic gene expression and downregulating myostatin expression. Furthermore, this extract reduced nitrotyrosine protein levels and atrophy-related gene expression. Of the five different fractions of the CWE of G. uralensis obtained, the ethyl acetate (EtOAc) fraction more significantly enhanced myoblast proliferation and differentiation than the other fractions. Ten bioactive compounds were isolated from the EtOAc fraction and characterized by GC-MS and NMR. Of these compounds (4-hydroxybenzoic acid, liquiritigenin, (R)-(-)-vestitol, isoliquiritigenin, medicarpin, tetrahydroxymethoxychalcone, licochalcone B, liquiritin, liquiritinapioside, and ononin), liquiritigenin, tetrahydroxymethoxychalcone, and licochalcone B were found to enhance myoblast proliferation and differentiation, and myofiber diameters in injured muscles were wider with the liquiritigenin than the non-treated one. Computational analysis showed these compounds are non-toxic and possess good drug-likeness properties. These findings suggest that G. uralensis-extracted components might be useful therapeutic agents for the management of muscle-associated diseases.


Assuntos
Glycyrrhiza uralensis/química , Atrofia Muscular/tratamento farmacológico , Extratos Vegetais/química , Animais , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Chalconas/química , Chalconas/farmacologia , Chalconas/uso terapêutico , Flavanonas/química , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mioblastos/citologia , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Miostatina/genética , Miostatina/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Tirosina/análogos & derivados , Tirosina/metabolismo
4.
Int J Pharm ; 595: 120181, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33359537

RESUMO

There is an unmet medical need for non-toxic and effective radiation countermeasures for prevention of radiation toxicity during planned exposures. We have earlier shown that intraperitoneal administration of baicalein (BCL) offers significant survival benefit in animal model. Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of baicalein has been reported in pre-clinical model systems and also in healthy human volunteers. However, clinical translation of baicalein is hindered owing to poor bioavailability due to lipophilicity. In view of this, we fabricated and characterized in-situ solid lipid nanoparticles of baicalein (SLNB) with effective drug entrapment and release kinetics. SLNB offered significant protection to murine splenic lymphocytes against 4 Gy ionizing radiation (IR) induced apoptosis. Oral administration of SLNB exhibited ~70% protection to mice against whole body irradiation (WBI 7.5 Gy) induced mortality. Oral relative bioavailability of BCL was enhanced by over ~300% after entrapment in the SLNB as compared to BCL. Oral dosing of SLNB resulted in transient increase in neutrophil abundance in peripheral blood. Interestingly, we observed that treatment of human lung cancer cells (A549) with radioprotective dose of SLNB exhibited radio-sensitization as evinced by decrease in survival and clonogenic potential. Contrary to antioxidant nature of baicalein in normal cells, SLNB treatment induced significant increase in cellular ROS levels in A549 cells probably due to higher uptake and inhibition of TrxR. Thus, a pharmaceutically acceptable SLNB exhibited improved bioavailability, better radioprotection to normal cells and sensitized cancer cells to radiation induced killing as compared to BCL suggesting its possible utility as an adjuvant during cancer radiotherapy.


Assuntos
Flavanonas/administração & dosagem , Flavanonas/farmacologia , Lipossomos/administração & dosagem , Lipossomos/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/administração & dosagem , Protetores contra Radiação/farmacologia , Células A549 , Administração Oral , Animais , Disponibilidade Biológica , Morte Celular/efeitos dos fármacos , Composição de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos , Flavanonas/farmacocinética , Flavanonas/uso terapêutico , Granulócitos/efeitos dos fármacos , Humanos , Lipossomos/farmacocinética , Lipossomos/uso terapêutico , Linfócitos/efeitos dos fármacos , Linfócitos/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/uso terapêutico , Tolerância a Radiação/efeitos dos fármacos , Protetores contra Radiação/farmacocinética , Protetores contra Radiação/uso terapêutico , Radioterapia/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo
5.
Front Immunol ; 11: 570919, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101291

RESUMO

Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic by the World Health Organization in March 2020. Severe COVID-19 cases develop severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. The higher risk group includes the elderly and subjects with pre-existing chronic illnesses such as obesity, hypertension, and diabetes. To date, no specific treatment or vaccine is available for COVID-19. Among many compounds, naringenin (NAR) a flavonoid present in citrus fruits has been investigated for antiviral and anti-inflammatory properties like reducing viral replication and cytokine production. In this perspective, we summarize NAR potential anti-inflammatory role in COVID-19 associated risk factors and SARS-CoV-2 infection.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Flavanonas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Replicação Viral/efeitos dos fármacos , Animais , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Modelos Animais de Doenças , Humanos , Macrófagos/imunologia , Pandemias , Pneumonia Viral/patologia
6.
Life Sci ; 261: 118463, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32950576

RESUMO

AIMS: Ionizing radiation (IR) induces injuries to the hematopoietic and intestinal systems, which are the leading cause of death. Baicalein, a plant-derived flavonoid, shows anti-oxidative stress, anti-apoptosis, anti-inflammation effects in many diseases. In this study, we evaluated the effects and mechanism of baicalein on IR induced intestinal and hematopoietic injuries. MAIN METHODS: Mice were divided into three groups: Control, IR and IR + Baicalein. All of mice were intraperitoneally administered with 100 mg/kg baicalein or normal saline for 1 h before IR, and then a day post-IR. The changes in intestinal structure, function and molecular expression were observed by pathological experiments and western blot. 16S rRNA gene sequencing was performed to analyze gut microbiota and further predicted metabolic pathways through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Hematopoietic function was evaluated by peripheral blood cells count and by flow cytometry analysis of hematopoietic cells composition. KEY FINDINGS: Baicalein improved intestinal structure and the ability of proliferation and regeneration after mice exposed to IR, in which the rebalance of gut microbial composition played an important role. KEGG results showed that p53-related apoptotic pathways played important roles in the composition changes of gut microbiota. Then we observed that baicalein inhibited the activation of p53 and p53 mediated mitochondrial apoptosis and death receptor apoptosis in the intestine. In addition, IR induced injuries to hematopoietic system also could be ameliorated by baicalein. SIGNIFICANCE: These results provide new insights into the mechanism of baicalein and support the potential of baicalein as a radioprotective medicine.


Assuntos
Flavanonas/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos da radiação , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Intestinos/efeitos dos fármacos , Intestinos/patologia , Intestinos/efeitos da radiação , Masculino , Camundongos Endogâmicos C57BL , Lesões Experimentais por Radiação/microbiologia , Lesões Experimentais por Radiação/patologia , Radiação Ionizante
7.
Life Sci ; 259: 118183, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32781058

RESUMO

Cancer, being a multifactorial disease has diverse presentation in different subgroups which is mainly attributed to heterogenous presentation of tumor cells. This cancer cell heterogeneity is the major reason for variable response to standard chemotherapeutic regimes owing to which high relapse rate and multi-drug resistance has increasingly been reported over the past decade. Interestingly, the research on natural compounds in combination with standard therapies have reported with interesting and promising results from the pre-clinical trials and few of which have also been tested in other phases of clinical trials. This review focusses on baicalein, an emerging anti-cancerous natural compound, its chemistry and mechanism of action. In view of promising pre-clinical this review is mainly motivated by the results observed from baicalein treatment of different cancer cell population. With the advancing scientific evidence on the anti-malignant potential of baicalein with respect to its pharmacological activities encompassing from anti-inflammatory to anti-angiogenic/anti-metastatic effects, the focus is mainly directed to understanding the precise mechanism of action of baicalein. In the process of understanding the underlying signaling cascades, the role of mitogen activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), AKT serine/threonine protein kinase B (AKT), poly(ADP-ribose) polymerase (PARP), matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9) and caspase-3/-8,-9 have been highlighted as the major players for baicalein anti-malignant potential. This is also supported by the interesting pre-clinical findings which cumulatively pave the way ahead for development of baicalein as an adjunct anti-cancer treatment with chemotherapeutic agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Neoplasias/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Apoptose/efeitos dos fármacos , Humanos , Metástase Neoplásica/prevenção & controle , Neoplasias/patologia
8.
AAPS PharmSciTech ; 21(6): 215, 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32743708

RESUMO

Naringenin (NAR) is a flavonoid found in citrus fruits such as grapes and oranges. Recently, NAR has demonstrated its potential in inhibition of photoaging. The aim of the present study was to investigate the efficacy of sericin (SR) gel loaded with NAR microemulsion (ME) to inhibit UVB-induced photoaging and prevention of epidermoid carcinoma in animal model. NAR -ME was prepared and optimized through Box-Behnken design. The optimized ME was loaded into sericin (SR) gel. The formulations were subjected to various in vitro, in vivo and cytotoxicity studies over A431 cell lines. The optimized ME revealed a globule size of 249.05 ± 3.78 nm, 6.7 ± 0.5 pH and 73.1 ± 2.11% release over a period of 24 h respectively. Cytotoxicity studies revealed a depression in IC50 value in NAR -ME (65.11 ± 1.54 µg/ml) when compared with NAR (118.1 ± 2.09 µg/ml). The NAR-ME-SR gel displayed enhanced therapeutic potential when compared with plain NAR, in terms of augmented antiproliferative activity. Graphical abstract.


Assuntos
Emulsões , Flavanonas/uso terapêutico , Sericinas/administração & dosagem , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Animais , Linhagem Celular , Géis , Ratos , Ratos Wistar
9.
Life Sci ; 257: 118118, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32702445

RESUMO

AIMS: Recent findings have instituted the role of hyperglycemia-related AGE/RAGE and NF-κB in instigating reactive oxygen species (ROS) mediated mitochondrial dysfunction and apoptosis of hepatocyte, which leads to steatohepatitis. Naringin, a flavanone glycoside found to possess myriads of pharmacological benefits along with its antioxidant and anti-inflammatory properties. Consequently, we aimed to decipher the effect of naringin on RAGE/NF-κB mediated mitochondrial apoptosis in type 2 diabetes mellitus (T2DM)-induced steatohepatitis. MAIN METHODS: Hepatic HepG2 cells were cultured in palmitic acid medium with and without naringin. Lipid content was examined by Oil Red O and Nile Red staining. Cellular apoptosis was determined by Annexin V-FITC/PI staining. An experimental T2DM-induced steatohepatitis was developed in Sprague Dawley rats by high-fat diet (HFD) for 12 weeks. The naringin was administrated orally at a dose of 100 mg/kg, daily for eight weeks. Glucose and insulin tolerance test was performed. Liver sections were stained by hematoxylin-eosin and picrosirius red. The mRNA and protein expression of RAGE and NF-κB were determined by qPCR, Immunofluorescence, and Immunoblotting. Mitochondrial membrane potential (MMP), cellular and mitochondrial ROS were measured by FACS. KEY FINDINGS: Palmitic acid encountered HepG2 cells and HFD fed rats exhibited hyperlipidemia, insulin resistance, abnormal aminotransferases, steatosis, and fibrosis. Besides, the level of AGEs, RAGE, NF-κB, and oxidative stress were exacerbated. Moreover, MMP, cellular and mitochondrial ROS were altered in diabetic rats. Nevertheless, the naringin treatment ameliorated the steatohepatitis by improving the levels of aforementioned parameters. SIGNIFICANCE: Collectively, these findings suggested anti-steatohepatitis potential of naringin in diabetics.


Assuntos
Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Fígado Gorduroso/tratamento farmacológico , Flavanonas/uso terapêutico , Mitocôndrias/efeitos dos fármacos , NF-kappa B/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Imunofluorescência , Teste de Tolerância a Glucose , Células Hep G2/efeitos dos fármacos , Humanos , Insulina/sangue , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
10.
J Pharmacol Sci ; 143(4): 300-306, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32534995

RESUMO

Drug and therapies currently used to treat human bone diseases have a lot of severe side effects. Liquiritigenin is a flavonoid extracted from Glycyrrhiza glabra roots which has been reported to have positive effects in vitro on osteoblasts activity and bone mineralization as well as inhibitory effect on osteoclasts differentiation and activity in vitro. The present study was aimed to evaluate the in vivo effects of liquiritigenin on bone structure and metabolism in physiological and pathological conditions using Danio rerio as experimental animal model. Treatments with liquiritigenin were performed on embryos to evaluate the osteogenesis during skeletal development. Other treatments were performed on adult fish affected by glucocorticoid-induced osteoporosis to assay the therapeutic potential of liquiritigenin in the reversion of bone-loss phenotype in scale model. Liquiritigenin treatment of zebrafish embryo significantly enhances the osteogenesis during development in a dose-dependent manner. In addition, liquiritigenin inhibits the formation of the osteoporotic phenotype in adult zebrafish model of glucocorticoid-induced osteoporosis preventing osteoclast activation in scales. Interestingly, liquiritigenin does not counteract the loss of osteoblastic activity in scales. The liquiritigenin exhibits in vivo anti-osteoporotic activity on adult fish scale model. It can be considered a good candidate to develop new drugs against osteoporosis.


Assuntos
Flavanonas/farmacologia , Flavanonas/uso terapêutico , Glucocorticoides/efeitos adversos , Osteoclastos/efeitos dos fármacos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Animais , Modelos Animais de Doenças , Osteogênese/efeitos dos fármacos , Estimulação Química , Peixe-Zebra
11.
Phytother Res ; 34(10): 2665-2674, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32281178

RESUMO

PURPOSE: The aim of the study was to investigate the effect of liquiritin on neuroendocrine-immune network in menopausal rat model. METHODS: Liquiritin groups were respectively given liquiritin suspension at the dose of 80, 40, and 20 mg/kg, once a day for continuous 30 days after the removal of bilateral ovaries to induce the menopausal rat model. Behavioral experiments were conducted and the organs were weighed for the viscera index. The content of estradiol (E2 ) and follicle-stimulating hormone (FSH) in the serum and 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in hypothalamus were assayed by enzyme linked immunosorbent assay kits. Morphological changes of uterus and adrenal gland were observed by hematoxylin-eosin (HE) staining and estrogen receptor (ER) expression of uterus and spleen were determined by immunohistochemical staining. RESULTS: For the nervous system, liquiritin relieved menopausal depression and up-regulated the levels of 5-HT and NE in hypothalamus; for the endocrine system, it raised the concentrations of E2 and FSH in serum, relieved the histological changes of uterus and adrenal gland and increased the expression of ER in uterus; for the immune system, it increased the thymus index and the expression of ER in spleen. CONCLUSIONS: Liquiritin improved menopausal syndrome in multiple ways by affecting the neuro-endocrine-immune network.


Assuntos
Flavanonas/uso terapêutico , Glucosídeos/uso terapêutico , Glycyrrhiza/química , Menopausa/efeitos dos fármacos , Sistemas Neurossecretores/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Feminino , Flavanonas/farmacologia , Glucosídeos/farmacologia , Ratos , Ratos Wistar
12.
Zhongguo Zhong Yao Za Zhi ; 45(3): 631-635, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237523

RESUMO

This paper was aimed to observe the interventional effect of Sedum sarmentosum total flavanones on hepatic fibrosis and its possible mechanism through the subcutaneous injection of CCl_4 in rats. Sixty male SD rats were randomly divided into normal control group, model group, low-dose, medium-dose, high-dose S. sarmentosum total flavanones groups(100, 200, 400 mg·kg~(-1)) and silymarin group(200 mg·kg~(-1)). The model of liver fibrosis was established by subcutaneous injection of rats with 40% CCl_4. After the modeling, the drug groups were intragastrically administered with corresponding drugs once a day for consecutively five weeks, while the normal group and the model group were given 0.9% sodium chloride solution during the same period. After the experiment, the general conditions of rats and the pathological changes of liver tissues were observed, and the contents of serum ALT, AST, HA and LN were measured. Besides, the expressions of the protein and relevant mRNA of Smad2/3, Smad4 and α-SMA in rats were detected. Compared with model group, S. sarmentosum total flavanones could significantly increase the rats' body weight, inhibit the increase of liver and spleen index in rats of liver fibrosis, reduce the levels of ALT, AST, HA and LN, and alleviate pathological changes. Meanwhile, compared with the model group, the protein expressions of Smad2/3, Smad4 and α-SMA as well as relevant mRNA expressions in S. sarmentosum total flavanones group were obviously decreased, while Smad7 expression was markedly increased. As a result, S. sarmentosum total flavanones could significantly alleviate CCl_4-induced liver fibrosis, and its anti-hepatic fibrosis mechanism may be related to intervention with Smads pathway, so as to inhibit the activation of HSC.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Flavanonas/uso terapêutico , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Sedum/química , Proteínas Smad/metabolismo , Animais , Tetracloreto de Carbono , Fígado , Cirrose Hepática/induzido quimicamente , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
13.
Mini Rev Med Chem ; 20(4): 286-293, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32134369

RESUMO

Flavonoids are an important class of phytopharmaceuticals in plants. Naringin (naringenin- 7-O-rhamnoglucoside) is a flavanone glycoside isolated from folk herbal medicine Exocarpium Citri grandis (called Huajuhong in Chinese). Massive experimental works have been performed on naringin describing its phytochemical, pharmacokinetic, and bioactive properties. Naringin was found to possess multiple pharmacological activities in relieving inflammation, diabetes, neurodegeneration, cardiovascular disorders, and metabolic syndrome. Recently, it has been approved as a potential antitussive and expectorant for clinical trials. However, the pharmacokinetic aspects of naringin and its therapeutic potentials in respiratory diseases have not been comprehensively reviewed. The present review provides highlights of naringin with respect to its absorption, distribution, metabolism, excretion and its therapeutic effects on cough, phlegm, and pulmonary inflammation. This review would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in clinical trials.


Assuntos
Flavanonas , Transtornos Respiratórios/tratamento farmacológico , Animais , Flavanonas/farmacocinética , Flavanonas/uso terapêutico , Humanos
14.
Life Sci ; 249: 117535, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32151688

RESUMO

AIM: Schizophrenia is a chronic, disabling and one of the major neurological illnesses affecting nearly 1% of the global population. Currently available antipsychotic medications possess limited effects. The current research aimed at investigating potential therapeutic add-on benefit to enhance the effects of clozapine anti-schizophrenic. MAIN METHODS: To induce schizophrenia, ketamine was administered at a dose of 25 mg/kg i.p. for 14 consecutive days. Naringin was administered to Wistar rats at a dose of 100 mg/kg orally, alone or in combination with clozapine 5 mg/kg i.p from day 8 to day 14. Furthermore, behavioral tests were conducted to evaluate positive, negative and cognitive symptoms of schizophrenia. In addition, neurotransmitters' levels were detected using HPLC. Moreover, oxidative stress markers were assessed using spectrophotometry. Furthermore, apoptotic and wnt/ß-catenin pathway markers were determined using western blotting (Akt, GSK-3ß and ß-catenin), colorimetric methods (Caspase-3) and immunohistochemistry (Bax, Bcl2 and cytochrome c). KEY FINDINGS: Ketamine induced positive, negative and cognitive schizophrenia symptoms together with neurotransmitters' imbalance. In addition, ketamine treatment caused significant glutathione depletion, lipid peroxidation and reduction in catalase activity. Naringin and/or clozapine treatment significantly attenuated ketamine-induced schizophrenic symptoms and oxidative injury. Additionally, ketamine provoked apoptosis via increasing Bax/Bcl2 expression, caspase-3 activity, and Cytochrome C and Akt protein expression while naringin/clozapine treatment significantly inhibited this apoptotic effect. Moreover, naringin activated the neurodevelopmental wnt/ß-catenin signaling pathway evidenced by increasing pGSK-3ß and reducing pß-catenin protein expression. SIGNIFICANCE: These findings may suggest that naringin possesses a potential therapeutic add-on effect against ketamine-induced schizophrenia.


Assuntos
Antipsicóticos/farmacologia , Flavanonas/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Ketamina/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Esquizofrenia/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Antipsicóticos/administração & dosagem , Antipsicóticos/uso terapêutico , Clozapina/administração & dosagem , Clozapina/farmacologia , Clozapina/uso terapêutico , Modelos Animais de Doenças , Flavanonas/administração & dosagem , Flavanonas/uso terapêutico , Masculino , Ratos , Ratos Wistar , Esquizofrenia/induzido quimicamente
15.
Phytother Res ; 34(8): 1734-1744, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32067280

RESUMO

The liver is a vital metabolic organ for drug and xenobiotic metabolism which is influenced by chemical and natural toxins. Liver injury is associated with systemic oxidative stress, which leads to cellular necrosis, fibrosis, tissue lipid peroxidation, and depletion in glutathione levels. Considering the lack of reliable hepato-protective drugs in modern medicine, plant-derived phytoconstituents seem to be a noteworthy option. Naringin is an abundant flavonoid found in citrus fruits with various pharmacological benefits such as antioxidant, anti-inflammatory, and antiapoptotic, activities. In this review, we summarize available data from recent studies about the hepatoprotective effects of naringin against chemical toxicants and discuss the possible mechanisms of actions.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Citrus/química , Flavanonas/uso terapêutico , Fígado/efeitos dos fármacos , Animais , Feminino , Flavanonas/farmacologia , Humanos , Masculino , Ratos
16.
Oxid Med Cell Longev ; 2020: 4650207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047577

RESUMO

Sirtuin 1 (SIRT1) enzyme plays a pivotal role in the regulation of many physiological functions. In particular, it is implicated in ageing-related diseases, such as cardiac hypertrophy, myocardial infarct, and endothelial dysfunction; moreover, its expression decreases with age. Therefore, an effective strategy to extend the lifespan and improve cardiovascular function is the enhancement of the expression/activity of SIRT1 with exogenous agents. The Citrus flavonoid naringenin (NAR) presents structural similarity with the natural SIRT1 activator resveratrol. In this study, we demonstrate through in vitro assays that NAR significantly activates SIRT1 enzyme and shows antisenescence effects. The binding mode of NAR into SIRT1 was detailed investigated through in silico studies. Moreover, chronic administration (for six months) of NAR (100 mg/kg/day) to 6-month-old mice leads to an enhancement of SIRT1 expression and a marked reduction of reactive oxygen species production in myocardial tissue. Furthermore, at the end of the treatment, the plasma levels of two well-known markers of cardiovascular inflammation, TNF-α and IL6, are significantly reduced in 12-month-old mice treated with NAR, as well as the cardiovascular risk (total cholesterol/HDL ratio) compared to control mice. Finally, the age-associated fibrotic remodeling, which is well detected through a Mallory trichrome staining in the vehicle-treated 12-month-old mice, is significantly reduced by the chronic treatment with NAR. Moreover, an improvement of myocardium functionality is highlighted by the enhancement of citrate synthase activity and stabilization of the mitochondrial membrane potential after NAR treatment. Taken together, these results suggest that a nutraceutical approach with NAR may have positive impacts on many critical hallmarks of myocardial senescence, contributing to improve the cardiac performance in aged subjects.


Assuntos
Envelhecimento/fisiologia , Antioxidantes/uso terapêutico , Flavanonas/uso terapêutico , Miocárdio/patologia , Sirtuína 1/metabolismo , Animais , Linhagem Celular , Senescência Celular/efeitos dos fármacos , Citrus , Citoproteção , Modelos Animais de Doenças , Humanos , Interleucina-6/metabolismo , Camundongos , Ligação Proteica , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/genética , Fator de Necrose Tumoral alfa/metabolismo
17.
Eur J Pharmacol ; 872: 172972, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32006559

RESUMO

Cisplatin is used as a first line therapy in treating cancers. However, its use is often accompanied with the development of peripheral neuropathy. 6-Methoxyflavanone (6-MeOF) is a positive allosteric modulator at GABAA receptors and is known for attenuating diabetes-induced neuropathic pain. Neuropathy was induced in male Sprague-Dawley rats (150-250 g), via intraperitoneal injection of cisplatin (3 mg/kg) once a week for four consecutive weeks. 6-MeOF (25, 50 and 75 mg/kg, i.p) and gabapentin (75 mg/kg, i.p) were administered 30 min before each cisplatin injection. Static and dynamic allodynia were assessed using von Frey filaments and cotton buds. The anti-inflammatory activity was analyzed with plethysmometer. Body weights were also measured each week. The binding affinity of 6-MeOF with chloride channel, Cyclooxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2) was studied using docking approach. The in vitro COX-1 and COX-2 inhibitory effect of 6-MeOF was conducted with COX colorimetric assay. Administration of cisplatin for four consecutive weeks induced static (decreased paw withdrawal threshold; PWT) and dynamic allodynia (decreased paw withdrawal latency; PWL). Co-administration of 6-MeOF for four weeks significantly attenuated the cisplatin-induced expression of nocifensive behaviors observed as significant increase in PWT and PWL. Moreover, it also prevented the body weight loss induced by cisplatin administration. In silico studies depicted a good interaction of 6-MeOF with chloride ion channels and COX-1 and COX-2 enzymes. The in vitro study confirmed the inhibitory activity of 6-MeOF for COX-1 and COX-2. 6-MeOF may be effective in attenuating cisplatin-induced allodynia, probably through interaction with GABAergic receptors and reducing inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Cisplatino/efeitos adversos , Flavanonas/farmacologia , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Receptores de GABA-A/metabolismo , Regulação Alostérica/efeitos dos fármacos , Regulação Alostérica/imunologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Flavanonas/química , Flavanonas/uso terapêutico , Humanos , Hiperalgesia/induzido quimicamente , Hiperalgesia/diagnóstico , Hiperalgesia/imunologia , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/imunologia , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Neoplasias/tratamento farmacológico , Neuralgia/induzido quimicamente , Neuralgia/diagnóstico , Neuralgia/imunologia , Ratos , Receptores de GABA-A/química , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
18.
Pharmacol Rep ; 72(1): 13-23, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32016847

RESUMO

BACKGROUND: The current strategies for prevention and treatment of insulin resistance and type 2 diabetes are not fully effective and frequently accompanied by many negative effects. Therefore, novel ways to prevent insulin resistance and type 2 diabetes are urgently needed. The roots of Scutellaria radix are commonly used in traditional Chinese medicines for prevention and treatment of type 2 diabetes, atherosclerosis, hypertension, hyperlipidemia, dysentery, and other respiratory disorders. Baicalin and baicalein are the major and active ingredient extracts from Scutellaria baicalensis. METHODS: A comprehensive and systematic review of literature on baicalin and baicalein was carried out. RESULTS: Emerging evidence indicated that baicalin and baicalein possessed hepatoprotective, anti-oxidative, anti-dyslipidemic, anti-lipogenic, anti-obese, anti-inflammatory, and anti-diabetic effects, being effective for treating obesity, insulin resistance, non-alcoholic fatty liver, and dyslipidemia. Besides, baicalin and baicalein are almost non-toxic to epithelial, peripheral, and myeloid cells. CONCLUSION: The purpose of this study is to focus on the therapeutic applications and accompanying molecular mechanisms of baicalin and baicalein against hyperglycemia, insulin resistance, type 2 diabetes, hyperlipidemia, obesity, and non-alcoholic fatty liver, and trying to establish a novel anti-obese and anti-diabetic strategy.


Assuntos
Flavanonas/uso terapêutico , Flavonoides/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Flavanonas/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Resistência à Insulina , Doenças Metabólicas/fisiopatologia , Obesidade/tratamento farmacológico , Obesidade/patologia , Scutellaria baicalensis/química
19.
Chin Med J (Engl) ; 133(3): 292-300, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31904729

RESUMO

BACKGROUND: Baicalein has been shown to have anti-inflammatory and anti-tumor activities. However, the mechanisms underlying its anti-inflammatory effect on colitis remain unclear. METHODS: A dextran sodium sulfate (DSS)-induced model of acute colitis was established in BALB/c mice (6-8 weeks old, weighing 18-22 g). Six groups of mice received: (1) water for 10 days (control), n = 6; (2) DSS 4% solution in the drinking water for 7 days, followed by normal water for 3 days, n = 7; (3), (4), and (5) as for group 2 plus baicalein (10, 20, 40 mg/kg) administered once daily starting on day 1, n = 6; and (6) as for (2) plus 5-aminosalicylic acid (50 mg/kg) administered once daily starting on day 1, n = 6. Body weights, stool consistency, and hematochezia were recorded, and the severity of colitis was evaluated using a disease activity index. On day 11, the mice were euthanized, and organs and blood were collected for analysis. Serum inflammatory factors were detected by enzyme-linked immunosorbent assay; CD11b-positive cells were analyzed by immunofluorescence microscopy; expression of retinoic-acid-receptor-related orphan nuclear receptor gamma, sphingosine kinase 1 (SPHK1), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) was detected by immunohistochemistry; and expression of nucleotide-binding oligomerization domain 2 (NOD2), SPHK1, sphingosine 1-phosphate receptor 1 (S1PR1), total STAT3, and p-STAT3 were detected by western blotting analysis. Inter-group differences were compared using Student's t test. RESULTS: Baicalein treatment dose-dependently reduced DSS-induced weight loss (P < 0.01 or P < 0.05), splenomegaly (P < 0.01), and colonic damage, as reflected by amelioration of diarrhea, rectal bleeding, and colonic ulceration, congestion, edema (shown as colon length, P < 0.05 or P < 0.01), and inflammatory cell infiltration. Baicalein also significantly decreased the levels of inflammatory mediators in the serum (P < 0.01) and colon, and significantly inhibited expression of NOD2 SPHK1, S1PR1, and p-STAT3 in the colon (P < 0.05). CONCLUSIONS: Baicalein treatment ameliorated colitis in mice by inhibiting S1P-STAT3 signaling, suggesting that this flavonoid might be beneficial in the treatment of colitis.


Assuntos
Colite/prevenção & controle , Flavanonas/uso terapêutico , Lisofosfolipídeos/fisiologia , Fator de Transcrição STAT3/fisiologia , Esfingosina/análogos & derivados , Animais , Colite/induzido quimicamente , Sulfato de Dextrana/farmacologia , Feminino , Flavanonas/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Proteína Adaptadora de Sinalização NOD2/análise , Fosfotransferases (Aceptor do Grupo Álcool)/análise , Fator de Transcrição STAT3/análise , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Esfingosina/fisiologia , Receptores de Esfingosina-1-Fosfato/análise
20.
Colloids Surf B Biointerfaces ; 185: 110635, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31744760

RESUMO

Wogonin, one of the main active ingredients of Scutellaria radix, is a kind of flavonoid compound. In the present study, we report that wogonin nanoparticles (Wog np) protect Isoproterenol (ISO) induced Myocardial Infarction (MI) rats. Nanoparticles of sizes less than 200 nm with spherical shape were prepared using Polylactic-co-glycolic acid (PLGA) and Polyvinyl alcohol (PVA) respectively as polymer and stabilizer. Male Wistar rats were divided into 4 groups. Group 1 as a control group administered with physiological saline solution with 0.5 % carboxymethylcellulose (1 mL/day). Group 2 served as toxic group; rats received physiological saline solution with 0.5 % carboxymethylcellulose (1 mL/day) orally for 21 days Groups 3 and 4 received Wog np (25 and 50 mg/kg/day) orally for 21 days and on the 20th and 21 st days group 2, 3, and 4 were administered with ISO (85 mg/kg) through s.c. route at 24 h interval. pre-treatment with Wog np (25 and 50 mg/kg) could significantly reduce the cardiac infarct size, serum cardiac markers, lipid peroxidation product (MDA) and inflammatory markers as well as markedly upregulated the protein expression of nuclear factor erythroid 2-related factor (Nrf2)and heme oxygenase-1 (HO-1) to confer its strong cardioprotective activity against ISO induced myocardial damage.


Assuntos
Cardiotônicos/uso terapêutico , Flavanonas/uso terapêutico , Inflamação/patologia , Infarto do Miocárdio/tratamento farmacológico , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Biomarcadores/sangue , Cardiotônicos/farmacologia , Citocinas/metabolismo , Liberação Controlada de Fármacos , Flavanonas/farmacologia , Heme Oxigenase-1/metabolismo , Mediadores da Inflamação/metabolismo , Isoproterenol , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/patologia , Miocárdio/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Nanopartículas/ultraestrutura , Oxidantes/toxicidade , Ratos Wistar
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...