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1.
Pol Merkur Lekarski ; 49(289): 44-53, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33713093

RESUMO

In the scope of this paper, an analysis of the clinical trial results assessing the clinical and immunological efficacy of the effects of flavonoids on some indicators of immunity in children and adults is given. AIM: The aim of the study was to evaluate the effects of flavonoids on the cellular component of the immune system in children and adults with viral and viral-bacterial diseases by using meta-analysis and statistical analysis of the clinical findings. MATERIALS AND METHODS: The analysis comprises 5 scientific sources with the results of controlled clinical trials involving 412 children and 15 sources involving 1493 adult patients during the period from 2003 to 2017. In analysis Student's t-test was applied. RESULTS: The data obtained indicate the efficacy of flavonoids in the treatment of viral and viral-bacterial diseases in children and adults. The administration of flavonoids (Proteflazid®, Immunoflazid®, Flavozid®) in the treatment of children with acute respiratory diseases and adults with HHV infection contributes to the normalization of cellular immunity indicators, the HHV infections symptom resolution, and the relapse rate reduction of genital herpes caused by HHV infection. CONCLUSIONS: Therapy with such medical products as Proteflazid®, Immunoflazid®, Flavozid® helps to improve the clinical status and normalize the cellular immunity indicators in patients who were administered a treatment course.


Assuntos
Flavonoides , Viroses , Adulto , Criança , Flavonoides/uso terapêutico , Humanos , Sistema Imunitário , Imunidade Celular
2.
BMC Complement Med Ther ; 21(1): 69, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607999

RESUMO

BACKGROUND: Endoplasmic reticulum stress (ERS) is one of the main mechanisms of spinal cord injury (SCI) pathology and can affect the physiological state of neurons. Icariin (ICA), the main pharmacological component of Epimedium, can relieve the symptoms of patients with SCI and has obvious protective effects on neurons through ERS. METHODS: PC12 cells were induced to differentiate into neurons by nerve growth factor and identified by flow cytometry. Cell proliferation was detected by CCK8 method, cell viability was detected by SRB assay, apoptosis was detected by flow cytometry and microstructure of ER was observed by transmission electron microscope. Western blot was used to detect the protein expression of CHOP and Grp78, and qPCR was used to detect the mRNA expression of CHOP and Grp78. RESULTS: The results of CCK8, SRB and flow cytometry showed that ICA could relieve ERS and reduce apoptosis of PC12 cells. The results of transmission microscope showed that ICA could reduce apoptosis of PC12 cells caused by ERS. The results of Western blot and q-PCR showed that ICA could inhibit ERS by down-regulating the expression of CHOP and Grp78. CONCLUSIONS: ICA can inhibit ERS and promote the repair of PC12 cells by down-regulating the expression of CHOP and Grp78. ICA has the potential to promote the recovery of spinal cord injury.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Epimedium/química , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Traumatismos da Medula Espinal/patologia , Animais , Apoptose , Proteínas de Transporte/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Flavonoides/uso terapêutico , Células PC12 , Extratos Vegetais/uso terapêutico , Ratos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Fator de Transcrição CHOP/metabolismo
3.
Food Chem ; 347: 129056, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476922

RESUMO

Flavonoid compounds have anti-diabetic activity, which can control blood glucose levels by inhibiting α-glucosidase activity. In this paper, the inhibition mechanisms between four flavonoid compounds and α-glucosidase were studied by multispectroscopic methods and molecular docking. The results showed that the inhibitory activities of flavonoid compounds were higher than that of acarbose, and the sequence of inhibition effect was scutellarein > nepetin > apigenin > hispidulin > acarbose. Also, the synergistic effects of flavonoid compounds combined with acarbose on inhibiting α-glucosidase activity were observed. The fluorescence results showed that flavonoid compounds combined with α-glucosidase to form a stable complex. And the spectral analysis indicated that the microenvironmental and secondary structure of α-glucosidase were changed. The present study demonstrated that the molecular structure of flavonoid compounds played an important role in the inhibition process, namely, scutellarein with more hydroxyl groups on the A-ring might serve as the most effective α-glucosidase inhibitor.


Assuntos
Acarbose/química , Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , alfa-Glucosidases/química , Acarbose/metabolismo , Apigenina/química , Apigenina/metabolismo , Sítios de Ligação , Diabetes Mellitus/tratamento farmacológico , Sinergismo Farmacológico , Flavonas/química , Flavonas/metabolismo , Flavonoides/metabolismo , Flavonoides/uso terapêutico , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Cinética , Simulação de Acoplamento Molecular , Termodinâmica , alfa-Glucosidases/metabolismo
4.
J Ethnopharmacol ; 264: 113322, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32871236

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Melastoma consists of approximately 100 species distributed widely in tropical and subtropical countries, and Melastoma species are often used for medicinal purposes, such as treatment for bleeding, diarrhea, diabetes, and gynecological tumors by local people, mostly in Southeast Asian countries. AIM OF THE REVIEW: The present review summarizes the traditional uses, phytochemistry and pharmacology of species belonging to Melastoma to suggest further research strategies and to facilitate the exploitation of the therapeutic potential of Melastoma species for the treatment of human disorders. MATERIALS AND METHODS: Information related to the traditional uses, phytochemistry and pharmacological activities was systematically collected by searching for the word "Melastoma" in electronic databases, including SciFinder, Web of Science, PubMed, and Google Scholar, from Apr. 1968 until Dec. 2019. RESULTS: A systematic literature survey revealed that Melastoma spp. are widely distributed in southern Asia to northern Oceania and the Pacific Islands and are traditionally used to treat bleeding, diarrhea, swelling, and gynecological tumors. Approximately 142 compounds, including flavonoids, tannins, phenylpropanoids, organic acids, terpenoids, and steroids, have been reported from Melastoma spp. Different extracts have been evaluated for their pharmacological activities, including anti-inflammatory, hemostatic, anticoagulant, cytotoxic, antibacterial, antioxidant, hepatoprotective, gastroprotective and hypoglycemic activities. CONCLUSIONS: Melastoma spp. are popularly used in Southeast Asian countries as effective herbs and are rich in flavonoids, tannins and organic acids with valuable medicinal properties. However, additional studies of the chemical constituents and the mechanism-based pharmacological activities of many members of Melastoma are still needed for developing new plant-derived drugs. In addition, studies on the clinical safety and efficacy of Melastoma are also needed.


Assuntos
Etnofarmacologia/métodos , Medicina Tradicional/métodos , Melastomataceae , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anticoagulantes/isolamento & purificação , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Etnofarmacologia/tendências , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Medicina Tradicional/tendências , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia
5.
J Ethnopharmacol ; 264: 113380, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32918994

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn is popularly used as a herbal medicine and food additive in the world. Sea buckthorn flavonoids (SF) is reported to have an ameliorative effect on obesity and hyperlipidemia (HLP). AIM: To identify the major bioactive compounds and the lipid-lowering mechanism of SF. METHODS: We used network pharmacology analysis and in vitro experiments to identify the major bioactive compounds and the lipid-lowering mechanism of SF. RESULTS: A total of 12 bioactive compounds, 60 targets related to SF and HLP were identified, and a component-target-disease network was constructed. The KEGG analysis revealed that SF regulated cholesterol metabolism, fat digestion and absorption, and PPAR signaling pathways in HLP. The experimental validation indicated that sea buckthorn flavonoids extract (SFE) and 4 bioactive compounds reduced lipid droplet accumulation, up-regulated the mRNA expression of PPAR-γ, PPAR-α, ABCA1 and CPT1A, etc, down-regulated SREBP-2 and its target gene LDLR, which are closely related to cholesterol conversion into bile acids, de novo synthesis and fatty acids oxidation. The major bioactive flavonoid isorhamnetin (ISOR) also increased the protein expression of PPAR-γ, LXRα and CYP7A1. CONCLUSION: SF might promote cholesterol transformation into bile acids and cholesterol efflux, inhibit cholesterol de novo synthesis and accelerate fatty acids oxidation for ameliorating HLP.


Assuntos
Flavonoides/farmacologia , Hippophae , Extratos Vegetais/farmacologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Flavonoides/isolamento & purificação , Flavonoides/uso terapêutico , Humanos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Mapas de Interação de Proteínas/fisiologia , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Reprodutibilidade dos Testes
6.
Life Sci ; 259: 118395, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32905830

RESUMO

In recent years, natural products have increasingly attracted more attention because of their potential anticancer activity and low intrinsic toxicity. Hispidulin is a natural flavonoid with a wide range of biological activities, including anti-inflammatory, antifungal, antiplatelet, anticonvulsant, anti-osteoporotic, and notably anticancer activities. Numerous in vivo and in vitro studies have shown that hispidulin, as a potential anticancer drug, affects cell proliferation, apoptosis, cell cycle, angiogenesis, and metastasis. Moreover, hispidulin exhibits synergistic anti-tumor effects when combined with some common clinical anticancer drugs (e.g., gemcitabine, 5-fluoroucil, sunitinib, temozolomide, and TRAIL). The combination of hispidulin and chemotherapeutic drugs reduces the efflux of chemotherapeutic drugs, enhances the chemosensitivity of cancer cells, and reverses drug resistance. Herein, we outlined the anticancer effects of hispidulin in various cancers and its intracellular molecular targets and related mechanisms of its anticancer activity. Based on the available literature, it can be established that hispidulin has significant potential to become an important complementary medicine for cancer prevention and treatment. However, more in-depth in vitro and in vivo studies should be conducted to support its translation from bench to bedside.


Assuntos
Antineoplásicos/uso terapêutico , Flavonas/uso terapêutico , Flavonoides/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico
8.
Cochrane Database Syst Rev ; 9: CD008294, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990945

RESUMO

BACKGROUND: Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress. This is an update of a previously published review. OBJECTIVES: To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders. SEARCH METHODS: We searched three databases and three trial registries; latest search: 30 September 2019. We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence. Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress. MAIN RESULTS: This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants). Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was low for four, high for one and unclear for 22 studies. In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV1) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV1 % predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence). In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence). In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence). In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence). In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence). In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence). In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence). In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence). For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events. AUTHORS' CONCLUSIONS: Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.


Assuntos
Antioxidantes/uso terapêutico , Doença Crônica/tratamento farmacológico , Flavonoides/uso terapêutico , Casca de Planta/química , Extratos Vegetais/uso terapêutico , Adolescente , Adulto , Asma/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Viés , Doenças Ósseas Metabólicas/tratamento farmacológico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Disfunção Erétil/tratamento farmacológico , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Osteoartrite/tratamento farmacológico , Pinus , Ensaios Clínicos Controlados Aleatórios como Assunto , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Insuficiência Venosa/tratamento farmacológico
9.
PLoS One ; 15(9): e0239315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970704

RESUMO

Anaplastic thyroid cancer (ATC) is a rare, but nearly uniformly fatal disease that is typically resistant to chemotherapy and radiation. Alternative strategies to target this cancer at a molecular level are necessary in order to improve dismal outcomes for ATC patients. We examined the effects of flavopiridol, a CDK inhibitor, in a panel of ATC cell lines. When cell lines were treated over a ten-point concentration range, CAL62, KMH2 and BHT-101 cell lines had a sub micromolar half-maximal inhibitory concentration, while no effect was seen in the non-cancerous cell line IMR-90. Flavopiridol treatment resulted in decreased levels of the cell cycle proteins CDK9 and MCL1, and induced cell cycle arrest. Flavopiridol also decreased the in vitro ability of ATC cells to form colonies and impeded migration using a transwell migration assay. In vivo, flavopiridol decreased tumor weight and tumor volume over time in a patient-derived xenograft model of ATC. Given the observed in vitro and in vivo activity, flavopiridol warrants further investigation for treatment of ATC.


Assuntos
Pontos de Checagem do Ciclo Celular , Flavonoides/uso terapêutico , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Quinase 9 Dependente de Ciclina/genética , Quinase 9 Dependente de Ciclina/metabolismo , Flavonoides/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Transplante Heterólogo
10.
Cell Prolif ; 53(10): e12894, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32881115

RESUMO

Cancer is the principal cause of death and a dominant public health problem which seriously threatening human life. Among various ways to treat cancer, traditional Chinese medicine (TCM) and natural products have outstanding anti-cancer effects with their unique advantages of high efficiency and minimal side effects. Cell senescence is a physiological process of cell growth stagnation triggered by stress, which is an important line of defence against tumour development. In recent years, active ingredients of TCM and natural products, as an interesting research hotspot, can induce cell senescence to suppress the occurrence and development of tumours, by inhibiting telomerase activity, triggering DNA damage, inducing SASP, and activating or inactivating oncogenes. In this paper, the recent research progress on the main compounds derived from TCM and natural products that play anti-cancer roles by inducing cell senescence is systematically reviewed, aiming to provide a reference for the clinical treatment of pro-senescent cancer.


Assuntos
Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Alcaloides/química , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Senescência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Neoplasias/patologia , Fenóis/química , Fenóis/farmacologia , Fenóis/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
11.
Life Sci ; 259: 118173, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32750437

RESUMO

The prevalence of various hepatic diseases increases dramatically worldwide and regarded as a serious health problem. Sirtuins are one of the main strategic controllers of different cellular processes, including cell cycle, mitochondrial biogenesis, insulin secretion, redox balance, inflammation, and apoptosis. SIRT1 is the most prominent and broadly studied member of sirtuins that implicated in health status and longevity. Therefore, targeting the SIRT1 signaling pathways may be a reasonable therapeutic approach to treat different diseases, including hepatic disorders. Flavonoids are polyphenolic compounds widely present in different plants and possess beneficial effects against diverse diseases. In this review, we focused on the flavonoids, (-)-epicatechin, ampelopsin, baicalin, delphinidin, fisetin, epigallocatechin-3-gallate, luteolin, pinocembrin, quercetin, silibinin, trans-chalcone and xanthohumol, to verify whether their potential promising hepatoprotective effects are related to activation of SIRT1. Additionally, molecular modeling simulations were applied to explore the potential binding mode of these flavonoids to SIRT1. The complied information and molecular docking simulations suggested that SIRT1 signaling is involved in the beneficial pharmacologic activities of flavonoids in different hepatic diseases.


Assuntos
Flavonoides/uso terapêutico , Hepatopatias/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/efeitos dos fármacos , Animais , Flavonoides/farmacologia , Humanos , Hepatopatias/fisiopatologia , Plantas/química
12.
Chem Biol Interact ; 328: 109211, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735799

RESUMO

In terms of public health, the 21st century has been characterized by coronavirus pandemics: in 2002-03 the virus SARS-CoV caused SARS; in 2012 MERS-CoV emerged and in 2019 a new human betacoronavirus strain, called SARS-CoV-2, caused the unprecedented COVID-19 outbreak. During the course of the current epidemic, medical challenges to save lives and scientific research aimed to reveal the genetic evolution and the biochemistry of the vital cycle of the new pathogen could lead to new preventive and therapeutic strategies against SARS-CoV-2. Up to now, there is no cure for COVID-19 and waiting for an efficacious vaccine, the development of "savage" protocols, based on "old" anti-inflammatory and anti-viral drugs represents a valid and alternative therapeutic approach. As an alternative or additional therapeutic/preventive option, different in silico and in vitro studies demonstrated that small natural molecules, belonging to polyphenol family, can interfere with various stages of coronavirus entry and replication cycle. Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PLpro, 3CLpro, NTPase/helicase. Due to their pleiotropic activities and lack of systemic toxicity, flavonoids and their derivative may represent target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Flavonoides/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Animais , Antivirais/química , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/genética , Betacoronavirus/fisiologia , Simulação por Computador , Coronaviridae/efeitos dos fármacos , Coronaviridae/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Avaliação Pré-Clínica de Medicamentos , Flavonoides/química , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Vírus da SARS/efeitos dos fármacos , Proteínas Virais/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos
13.
Rev Cardiovasc Med ; 21(2): 275-287, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706215

RESUMO

Inflammation and oxidative stress are involved in the pathogenesis of cardiovascular diseases such as atherosclerosis, hypertension and ischemic heart disease. Natural products play an important role as nutritional supplements with potential health benefits in cardiovascular diseases. Polygonum minus (PM) is an aromatic plant that is widely used as a flavoring agent in cooking and has been recognized as a plant with various medicinal properties including antioxidative and anti-inflammatory actions. Phytoconstituents found in PM such as phenolic and flavonoid compounds contribute to the plant's antioxidative and anti-inflammatory effects. We conducted this review to systematically identify articles related to the antioxidative and anti-inflammatory activities of PM. A computerized database search was conducted on Ovid MEDLINE, PubMed, Scopus, and ACS publication, from 1946 until May 2020, and the following keywords were used: 'Kesum OR Polygonum minus OR Persicaria minor' AND 'inflammat* OR oxida* OR antioxida*'. A total of 125 articles were obtained. Another eight additional articles were identified through Google Scholar and review articles. Altogether, 17 articles were used for data extraction, comprising 16 articles on antioxidant and one article on anti-inflammatory activity of PM. These studies consist of 14 in vitro studies, one in vivo animal study, one combined in vitro and in vivo study and one combined in vitro and ex vivo study. All the studies reported that PM exhibits antioxidative and anti-inflammatory activities which are most likely attributed to its high phenolic and flavonoid content.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Flavonoides/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Polygonum/química , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/efeitos adversos , Antioxidantes/isolamento & purificação , Flavonoides/efeitos adversos , Flavonoides/isolamento & purificação , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Transdução de Sinais
14.
Nihon Yakurigaku Zasshi ; 155(4): 209-213, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32612030

RESUMO

The number of patients with type 2 diabetes mellitus (T2DM) has rapidly increased, especially in East and Southeast Asia. In these areas, in general, people have especially vulnerable ß-cells and insulin secretion deficiency and reduced ß-cell mass are the primary cause of T2DM. Therefore, the alleviation of such ß-cell dysfunction would provide therapeutic approaches to prevent the development of T2DM. Nobiletin, a polymethoxylated flavonoid found in citrus fruits, has been shown to improve obesity and insulin resistance in T2DM model mice. We focused on ß-cells and investigated the effects of nobiletin on insulin secretion and ß-cell apoptosis. In ß-cell line INS-1, nobiletin increased glucose-induced insulin secretion (GSIS) in a concentration-dependent manner, which was inhibited by an Epac inhibitor. In addition, nobiletin at 10 µM inhibited thapsigargin-induced apoptosis, which was inhibited by a PKA inhibitor. Nobiletin also suppressed thapsigargin-induced increases in cleaved caspase-3 and phosphorylated JNK. Thus, nobiletin is suggested to promote GSIS and prevent ER stress-induced ß-cell apoptosis, which are mediated via Epac and PKA-dependent pathways, respectively. In summary, nobiletin is suggested to exhibit insulinotropic and anti-apoptotic effects on ß-cells, which are one of the causes of its anti-diabetic effect. Moreover, nobiletin seems to be able to alleviate the development of T2DM by protecting ß-cells from apoptosis.


Assuntos
Citrus , Diabetes Mellitus Tipo 2 , Flavonas , Células Secretoras de Insulina , Animais , Apoptose , Diabetes Mellitus Tipo 2/tratamento farmacológico , Flavonas/farmacologia , Flavonas/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Camundongos
15.
Clin Sci (Lond) ; 134(12): 1403-1432, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32556180

RESUMO

Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.


Assuntos
Tecido Adiposo/patologia , Aterosclerose/tratamento farmacológico , Flavonoides/uso terapêutico , Inflamação/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aterosclerose/complicações , Flavonoides/química , Flavonoides/farmacologia , Humanos , Inflamação/complicações , Modelos Biológicos
16.
Chem Biol Interact ; 327: 109186, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32590071

RESUMO

In this study, we scrutinized the anticancer effects of FB-15 on human gastric carcinoma MGC-803 cells in vitro and vivo, and its preliminary effect on tubulin and HIF-1α. We confirmed that FB-15 not only inhibited the proliferation of a large number of cells in a concentration and time-dependent manner but also inhibited proliferation of a single cell to form clones. FB-15 manifested little cytotoxicity for normal stomach cells GES-1. The flow cytometry analysis displayed that FB-15 induced apoptosis MGC-803 cells and mainly arrested cells in the S phase in a concentration-dependent manner. The results of the wound healing assay indicated that FB-15 suppressed cell migration. Furthermore, the western blotting showed that FB-15 down-regulated the expression of ß3-tubulin and HIF-1α, consistent with Immunohistochemical assay. The binding modes of FB-15 with tubulin were clarified by molecular docking. FB-15 significantly suppressed the growth of MGC-803 gastric cancer tumors. The inhibitory effect of FB-15 on tumor growth was superior to 5-Fu. Taken together, these results provided evidence for FB-15 to be used as an effective anticancer drug candidate for gastric cancer.


Assuntos
Antineoplásicos/uso terapêutico , Benzimidazóis/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Flavonoides/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzimidazóis/metabolismo , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Flavonoides/metabolismo , Flavonoides/farmacologia , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Simulação de Acoplamento Molecular , Ligação Proteica , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Neoplasias Gástricas/patologia , Tubulina (Proteína)/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Toxicol Appl Pharmacol ; 400: 115070, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32464219

RESUMO

Vascular dysfunction plays a critical role in the pathogenesis of sepsis. We elucidated the mechanisms underlying the amelioration of lipopolysaccharide (LPS)-induced vascular inflammation by oroxylin A (OroA) post-treatment in rats. The animals were intraperitoneally injected with LPS (10 mg/kg) to induce systemic inflammation and intravenously (iv) administered OroA (15 mg/kg) 6 h after the LPS treatment. The assessments included biochemical changes in peripheral blood, vascular reactivity which was evaluated by blood-vessel myography, morphological/histological assessment of inflammation, toll-like receptor (TLR)-4-mediated interleukin-1-receptor-associated-kinase (IRAK)-4 activation, changes in adhesion molecule expression, and endothelial junctional stability in the aorta. LPS significantly enhanced the proinflammatory cytokine release, increased vascular cell adhesion molecule (VCAM)-1 expression, disrupted endothelial tight junction, reduced vascular endothelial barrier stability, and increased macrophage infiltration and accumulation in the aorta. All observed pathological changes and vascular inflammation were significantly reversed by the OroA post-treatment. Importantly, OroA suppressed the increased adhesion molecule expression and the endothelial barrier disruption by inhibiting LPS-activated IRAK-4-targeted inhibitory nuclear factor kappa B kinase (IKK) α/ß complex phosphorylation, without directly affecting the interaction between LPS and TLR-4. Moreover, the iNOS activity induced by the LPS challenge was inhibited by the OroA pretreatment of the isolated aortic rings. These results suggest that OroA regulates the vascular tone by inhibiting vascular hyporeactivity caused by NO overproduction and reverses the endothelial barrier dysfunction and inflammation by inhibiting the IRAK-4-mediated IKKα/ß phosphorylation. Overall, these findings suggest OroA administration as a potentially useful therapeutic approach for clinical interventions in septic shock.


Assuntos
Aorta/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Flavonoides/farmacologia , Sepse/prevenção & controle , Molécula 1 de Adesão de Célula Vascular/genética , Animais , Aorta/imunologia , Aorta/patologia , Células Cultivadas , Quimiocina CCL2/sangue , Citocinas/sangue , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Endotoxinas/farmacologia , Flavonoides/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Ratos Sprague-Dawley , Sepse/sangue , Sepse/patologia
18.
Chem Biol Interact ; 325: 109124, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32437694

RESUMO

The prenylated flavonoid icaritin (ICT) is currently undergoing phase 3 clinical trial for the treatment of advanced hepatocellular carcinoma (HCC), based on a solid array of preclinical and clinical data. The antitumor activity originates from the capacity of the drug to modulate several signaling effectors in cancer cells, mainly the estrogen receptor splice variant ERα36, the transcription factors STAT3 and NFκB, and the chemokine receptor CXCR4. Recent studies have implicated additional components, including different microRNAs, the generation of reactive oxygen species and the targeting of sphingosine kinase-1. ICT also engages the RAGE-HMGB1 signaling route and modulates the apoptosis/autophagy crosstalk to promote its anticancer activity. In addition, ICT exerts profound changes on the tumor microenvironment to favor an immune-response. Collectively, these multiple biochemical and cellular characteristics confer to ICT a robust activity profile which can be exploited to treat HCC, as well as other cancers, including glioblastoma and onco-hematological diseases such as chronic myeloid leukemia. This review provides an update of the pharmacological properties of ICT and its metabolic characteristics. It also addresses the design of derivatives, including both natural products and synthetic molecules, such as SNG1153 also in clinical trial. The prenylated flavonoid ICT deserves attention as a multifunctional natural product potentially useful to improve the treatment of advanced hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Flavonoides/química , Flavonoides/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Prenilação , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Desenho de Fármacos , Flavonoides/uso terapêutico , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo
19.
Phytomedicine ; 71: 153240, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32450461

RESUMO

BACKGROUND: Bioflavonoids, secondary metabolites of plants, are beneficial in regulating human physiological mechanisms. Bioflavonoids majorly exist in the dietary intake of fruits, vegetables, legumes, pulses, etc. In addition to their cardio-protective and neuroprotective activities, they also possess prominent pharmacological effects including anti-oxidant, anti-inflammatory, anti-proliferative and anti-thrombogenic actions. However, therapeutic efficacy of the bioflavonoids is hampered by their lipophilic nature, low solubility and variable bioavailability which catch the eyes of formulation scientists. PURPOSE: Nanocrystal formulations were studied for many bioflavonoids, although enough attention has not been given to their commercial exploitation, unlike drug nanocrystals. Nanocrystals of bioflavonoid can be prepared by top-down technique, bottom-up technique or combination of both. This review primarily focuses on nanocrystal technology for bioflavonoids, methods of production, critical process parameters, in vitro and in vivo studies conducted to evaluate the efficiency. METHOD: The detailed literature survey was systematically carried out using different electronic databases. It includes Scopus, Web of Science, Medline via PubMed, EMBASE, and Google Scholar. Also up-to-date patent search was conducted to understand the prior art and available intellectual properties. RESULT AND CONCLUSION: It was observed that several formulation and process parameters have an impact on flavonoids nanocrystals and their therapeutic efficacy. Also, clinical studies of flavonoid nanocrystals are barely done so far and thus, substantial safety and efficacy data is necessary for its commercial applications. Nevertheless, nanocrystals can be explored as a promising technology platform for improving overall therapeutic performance of flavonoids in future.


Assuntos
Flavonoides/química , Flavonoides/farmacologia , Nanopartículas/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Disponibilidade Biológica , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/farmacologia , Flavonoides/uso terapêutico , Humanos , Nanopartículas/uso terapêutico , Solubilidade
20.
Zhonghua Yan Ke Za Zhi ; 56(5): 376-382, 2020 May 11.
Artigo em Chinês | MEDLINE | ID: mdl-32450671

RESUMO

Objective: To explore the potential neuroprotection effects and associated mechanism of baicalin in a rodent acute hypertensive glaucoma model and oxygen-glucose deprivation/reperfusion (OGD/R) induced retinal ganglion cell (RGC) injury. Methods: Experiment research. A rapid and substantial elevation of intraocular pressure was performed to establish an acute hypertensive glaucoma model, and retinal thickness was assessed at 1, 3, 5, and 7 days. The mice were then randomly divided into three groups: normal control group, hypertension group, and baicalin (50 mg/kg) for hypertension group. The effects of baicalin on the RGCs were evaluated by retrograde transporting of Fluoro-Gold. The mRNA levels of tumor necrosis factor-α, interleukine-1ß (IL-1ß), and inducible nitric oxide synthase were detected by real-time PCR, and the protein levels were measured by Western blot in the retina tissue of acute hypertensive glaucoma model. Purified primary RGC survival under OGD/R stress was measured by flow cytometry, which was also performed to measure the survival rate of RGCs pretreated by different doses of baicalin (2.5 µmol/L, 5.0 µmol/L, and 10.0 µmol/L). The effects of baicalin on primary RGCs co-cultured with mouse microglia cell line BV2 were evaluated by flow cytometry. The cytokine IL-1ß in the culture supernatant was measured by immunochemical analyses. Statistical analysis was performed using analysis of variance. Results: Retinal tissue injuries and RGC loss were observed both in vivo and in vitro. Retinal thickness was decreased to 87.32%±0.94% at 3 days (t=6.73, P<0.01), 74.86%±2.43% at 5 days (t=13.40, P<0.01), and 63.53%±2.15% at 7 days (t=19.46, P<0.01). Treatment of 50 mg/kg baicalin significantly promoted the RGC survival from 61.32%±5.94% to 89.93%±10.08% (t=4.84, P<0.01). Baicalin alleviated the retinal damages by suppressing the expression of inflammatory cytokines as revealed by Western blot and real-time PCR. In vitro the RGC survival under OGD/R stress was increased from 51.53%±1.36% to 69.37%±7.09% and 66.23%±4.25% with 5.0, 10.0 µmol/L baicalin administration (t=5.50, 4.53; both P<0.01). BV2 under OGD/R stress did extra damage to RGCs, and baicalin could reverse the damages and increase the survival from 69.37%±7.09% to 73.00%±5.20% (t=2.82, P=0.048) by reducing the release of IL-1ß [(39.97±8.76) pg/ml vs. (61.33±5.78) pg/ml, t=4.19, P=0.010]. Conclusion: Baicalin could alleviate retina tissue injury directly and promote the survival of RGCs by downregulating the expression of inflammatory cytokines and protecting RGCs from ischemia reperfusion injury. (Chin J Ophthalmol, 2020, 56: 376-382).


Assuntos
Anti-Inflamatórios não Esteroides , Flavonoides , Glaucoma , Hipertensão Ocular , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Modelos Animais de Doenças , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Glaucoma/tratamento farmacológico , Camundongos , Hipertensão Ocular/tratamento farmacológico , Células Ganglionares da Retina
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