Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.028
Filtrar
1.
Antiviral Res ; 181: 104878, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32679055

RESUMO

In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.99, 5.2, 1.38, 3.5, 10.6 and 3 µM, respectively. Virus-directed plus host-directed drug combinations were also investigated. We report a strong antagonism between remdesivir and berberine, in contrast with remdesivir/diltiazem, for which we describe high levels of synergy, with mean Loewe synergy scores of 12 and peak values above 50. Combination of host-directed drugs with direct acting antivirals underscore further validation in more physiological models, yet they open up interesting avenues for the treatment of COVID-19.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Pandemias , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Animais , Berberina/farmacologia , Chlorocebus aethiops , Cloroquina/farmacologia , Infecções por Coronavirus/virologia , Ciclosporina/farmacologia , Antagonismo de Drogas , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Indóis/farmacologia , Lopinavir/farmacologia , Pneumonia Viral/virologia , Células Vero
2.
Int J Nanomedicine ; 15: 3937-3951, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581538

RESUMO

Purpose: Berberine (BBR), a major ingredient extracted from Coptis chinensis, is a natural drug with limited oral bioavailability. We developed nanostructured lipid carriers (NLCs) as a delivery system for enhanced anti-inflammatory activity of BBR against ulcerative colitis (UC). Methods: BBR-loaded nanostructured lipid carriers (BBR-NLCs) prepared via high-pressure homogenization were evaluated for particle size, zeta potential, drug entrapment efficiency, drug loading, drug release, toxicity, and cellular uptake. The anti-UC activities of free and encapsulated BBR were evaluated in a DSS-induced acute model of UC in mice. Results: Spherical BBR-NLCs were prepared with a particle size of 63.96± 0.31 nm, a zeta potential of +3.16 ± 0.05 mV, an entrapment efficiency of 101.97±6.34%, and a drug loading of 6.00±0.09%. BBR-NLCs showed excellent biocompatibility in vivo. Cellular uptake experiments showed that BBR-NLCs improved uptake of BBR by RAW 264.7 cells and Caco-2 cells. Oral administration of BBR-NLCs significantly alleviated colitis symptoms (DAI, colon length, spleen swelling, MPO activity) through inhibition of NF-κB nuclear translocation, decreased expression of pro-inflammatory cytokines (IL-1ß, IL-6, MMP-9, CX3CR1, COX-2, TERT), and increased expression of the tight junction protein ZO-1. Conclusion: BBR-loaded NLCs improved colitis symptoms, which suggested that this may be a novel formulation for treatment of UC.


Assuntos
Anti-Inflamatórios/administração & dosagem , Berberina/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Portadores de Fármacos/química , Lipídeos/química , Nanoestruturas/química , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Berberina/farmacocinética , Berberina/farmacologia , Células CACO-2 , Colite Ulcerativa/induzido quimicamente , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Portadores de Fármacos/administração & dosagem , Liberação Controlada de Fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Tamanho da Partícula , Células RAW 264.7
3.
Arch Virol ; 165(9): 1935-1945, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32594322

RESUMO

Plants are a rich source of new antiviral, pharmacologically active agents. The naturally occurring plant alkaloid berberine (BBR) is one of the phytochemicals with a broad range of biological activity, including anticancer, anti-inflammatory and antiviral activity. BBR targets different steps in the viral life cycle and is thus a good candidate for use in novel antiviral drugs and therapies. It has been shown that BBR reduces virus replication and targets specific interactions between the virus and its host. BBR intercalates into DNA and inhibits DNA synthesis and reverse transcriptase activity. It inhibits replication of herpes simplex virus (HSV), human cytomegalovirus (HCMV), human papillomavirus (HPV), and human immunodeficiency virus (HIV). This isoquinoline alkaloid has the ability to regulate the MEK-ERK, AMPK/mTOR, and NF-κB signaling pathways, which are necessary for viral replication. Furthermore, it has been reported that BBR supports the host immune response, thus leading to viral clearance. In this short review, we focus on the most recent studies on the antiviral properties of berberine and its derivatives, which might be promising agents to be considered in future studies in the fight against the current pandemic SARS-CoV-2, the virus that causes COVID-19.


Assuntos
Antivirais/farmacologia , Berberina/farmacologia , Vírus/efeitos dos fármacos , Animais , Antivirais/química , Berberina/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Viroses/virologia , Replicação Viral/efeitos dos fármacos , Vírus/genética , Vírus/crescimento & desenvolvimento
4.
Biofouling ; 36(3): 319-331, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32410461

RESUMO

Traditional herbal monomers (THMs) are widely distributed in many traditional Chinese formulas (TCFs) and decoctions (TCDs) and are frequently used for the prevention and treatment of fungal infections. The antifungal activities of five common THMs, including sodium houttuyfonate (SH), berberine (BER), palmatine (PAL), jatrorrhizine (JAT) and cinnamaldehyde (CIN), and their potential for inducing cell wall remodeling (CWR), were evaluated against Candida albicans SC5314 and Candida auris 12372. SH/CIN plus BER/PAL/JAT showed synergistic antifungal activity against both Candida isolates. Furthermore, SH-associated combinations (SH plus BER/PAL/JAT) induced stronger exposure of ß-glucan and chitin than their counterparts, while CIN triggered more marked exposure compared with CIN-associated combinations (CIN plus BER/PAL/JAT). Collectively, this study demonstrated the anti-Candida effect and the CWR induction potential of the five THMs and their associated combinations, providing a possibility of their in vivo application against fungal-associated infections.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Acroleína/análogos & derivados , Acroleína/farmacologia , Alcanos/farmacologia , Berberina/análogos & derivados , Berberina/farmacologia , Alcaloides de Berberina/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Sulfitos/farmacologia
5.
PLoS One ; 15(5): e0232630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32357187

RESUMO

Inflammation plays an essential role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Berberine (BBR), an isoquinoline alkaloid isolated from Chinese medicinal herbs, has been widely used to treat various diseases, including liver diseases for hundreds of years. The previous studies have shown that BBR inhibits high fat-diet-induced steatosis and inflammation in rodent models of NAFLD. However, the underlying molecular mechanisms remain unclear. This study is aimed to identify the potential mechanisms by which BBR inhibits free fatty acid (FFA) and LPS-induced inflammatory response in mouse macrophages and hepatocytes. Mouse RAW264.7 macrophages and primary mouse hepatocytes were treated with palmitic acid (PA) or LPS or both with or without BBR (0-10 µM) for different periods (0-24 h). The mRNA and protein levels of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, MCP-1) and ER stress genes (CHOP, ATF4, XBP-1) were detected by real-time RT-PCR, Western blot and ELISA, respectively. The results indicated that BBR significantly inhibited PA and LPS-induced activation of ER stress and expression of proinflammatory cytokines in macrophages and hepatocytes. PA/LPS-mediated activation of ERK1/2 was inhibited by BBR in a dose-dependent manner. In summary, BBR inhibits PA/LPS-induced inflammatory responses through modulating ER stress-mediated ERK1/2 activation in macrophages and hepatocytes.


Assuntos
Berberina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Berberina/uso terapêutico , Citocinas/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Ácido Palmítico/toxicidade , Células RAW 264.7
6.
Zhonghua Gan Zang Bing Za Zhi ; 28(4): 338-344, 2020 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-32403887

RESUMO

Objective: To observe the curative effects of berberine in rats with high-fat diet induced non-alcoholic fatty liver and to further explore its possible mechanism. Methods: Twenty-six Sprague-Dawley rats (120-160 g) were randomly divided into 3 groups: control group (n = 8), model group (n = 10) and treatment group (n = 8). Rats in the control group were fed with regular diet, and the model group and the treatment group were fed a high-fat diet. At the 12th week, two rats in the in the model group were sacrificed to verify whether model was successful established. Subsequently, treatment group rats were given a gavage of berberine at a dose of 150 mg·kg(-1)·d(-1) for 4 weeks, and the control and the model group rats were given the same dose of normal saline. Rats were sacrificed at week 16th. HE staining was used to observe the changes in the intestinal mucosa of rats. Sudan black B staining was used to observe the fatty changes in liver. Immunohistochemical staining was used to observe the expression level of occludin protein in the intestinal epithelium. A real-time 16S rDNA PCR method was used to measure the number of escherichia coli, bacteroides and faecalibacterium prausnitzii in the feces of rats. Results: Model group had a higher serum levels of endotoxin (0.288 ± 0.045) and tumor necrosis factor (TNF)-α (1.07 ± 0.11) than the control group (0.192 ± 0.049, 0.94 ± 0.07) (P < 0.05). Berberine intervention had significantly reduced endotoxin (0.213 ± 0.025) and TNF-α level (0.93 ± 0.07) (P < 0.05). The expression level of occludin protein was significantly lower in the intestinal mucosa of model group than that of control group (0.166 ± 0.014), and berberine had promoted the expression of occludin protein in intestinal mucosa (0.055 ± 0.009), but the difference was not statistically significant (P > 0.05). At the same time, compared with the model group (7.29 ± 0.47), the number of bacteroidetes in the control group (9.49 ± 0.59) was decreased, while the number of bacteroidetes in the treatment group was increased (9.77 ± 0.87). The number of escherichia coli (6.92 ± 0.77) and faecalibacterium prausnitzii (8.70 ± 0.62) in the model group were increased than control group (5.42 ± 0.63, 9.49 ± 0.59), while the number of escherichia coli (6.34 ± 0.71) and faecalibacterium prausnitzii (9.77 ± 0.87) (P < 0.05) was reduced with the intervention of berberine. Conclusion: Berberine could effectively protect the intestinal barrier function in rats with NAFLD and the possible mechanism of action behind it may be the regulation of intestinal flora.


Assuntos
Berberina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Dieta Hiperlipídica , Fígado , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
7.
Zhongguo Zhong Yao Za Zhi ; 45(3): 664-673, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237527

RESUMO

To evaluate the clinical efficacy and safety of berberine in the treatment of dyslipidemia. In this review, CNKI, WanFang, VIP, CBM, PubMed, Cochrane Library, EMbase, and Medline(OVID) were retrieved from database establishment to January, 2019 in any language. Randomized controlled trials(RCTs) of berberine with or without lipid-lowering drugs vs placebo, without drugs or lipid-lowering drugs only in treatment of dyslipidemia were collected. Data extraction and paper quality assessment were conducted according to the Cochrane Handbook. Then RevMan 5.3 software was used for Meta-analysis. A total of 25 trials were included, covering 3 042 cases, including 1 552 cases in the experimental group and 1 490 cases in the control group. The clinical heterogeneity of the included trials was relatively high, and the methodological quality of most trials was generally low, with bias in terms of random sequence generation, allocation hiding, blind method and result data. Interventions were divided into different subgroups for analysis. Meta-analysis suggested that use berberine alone or along with lipid lowing drugs could reduce TC, TG, LDL-C levels and increased HDL-C levels with statistically significant difference as compared with control group. As compared with control group, there was no statistically significant difference in the incidence of adverse events. No severe adverse effects were reported in all trials. Berberine has good efficacy and safety in the treatment of dyslipidemia. Due to the quality limitations of the included trials, the above conclusions need to be further verified by high-quality, large sample size and multi-center clinical trials.


Assuntos
Berberina/uso terapêutico , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Berberina/efeitos adversos , Humanos , Lipídeos , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Life Sci ; 252: 117637, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32251633

RESUMO

BACKGROUND: Berberine plays a neuroprotective role in neurodegenerative diseases, including Alzheimer's disease (AD). Circular RNAs (circRNAs) function as crucial players in AD pathogenesis. In the current work, we aimed to investigate whether circRNA histone deacetylase 9 (circHDAC9) was involved in the regulation of berberine in AD. METHODS: Cell viability and apoptosis were determined by the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to assess caspase-3 activity and the production of interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α). The levels of circHDAC9 and miR-142-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular fractionation assays were performed to evaluate the localization of circHDAC9. The direct interaction between circHDAC9 and miR-142-5p was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. RESULTS: Our data indicated that circHDAC9 was indeed a circular transcript and mainly localized in the cytoplasm. 42-residue ß-amyloid (Aß42) triggered a significant down-regulation in circHDAC9 and a striking up-regulation in miR-142-5p in human neuronal (HN) cells. Berberine relieved Aß42-induced HN cell neurotoxicity. Moreover, berberine resulted in increased circHDAC9 expression and decreased miR-142-5p level in Aß42-treated HN cells. Berberine alleviated Aß42-induced neuronal damage in HN cells by up-regulating circHDAC9. Furthermore, circHDAC9 acted as a molecular sponge of miR-142-5p. CircHDAC9 overexpression alleviated Aß42-induced HN cell neurotoxicity via miR-142-5p. CONCLUSION: Our current study suggested that berberine protected HN cell from Aß42-induced neuronal damage at least partly through regulating the circHDAC9/miR-142-5p axis, highlighting novel evidence for the neuroprotective effect of berberine in AD.


Assuntos
Berberina/farmacologia , Histona Desacetilases/genética , MicroRNAs/genética , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas Repressoras/genética , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/toxicidade , Apoptose/efeitos dos fármacos , Sobrevivência Celular , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Humanos , Neurônios/patologia , Fragmentos de Peptídeos/toxicidade , RNA Circular/genética , Regulação para Cima
9.
PLoS One ; 15(4): e0231466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298294

RESUMO

DaHuangWan (DHW) is a traditional herbal medicine used by Mongolian to treat liver cancer for many years. Clinical application of the drug has been shown to help control tumor progression, prolong survival and improve quality of life. However, the underlying mechanisms and side effects of this drug remain unclear, which greatly limits the clinical application and further optimization of DHW. In this study, we found that DHW inhibits the proliferation of hepatoma cells by modulating the epithelial growth factor (EGF) signaling pathway. Berberine and Costunolide are the main active ingredients in DHW. Interestingly, the combination of Berberine and Costunolide has a dramatic synergistic effect on inhibiting the proliferation of hepatoma cells. Neither Berberine nor Costunolide directly block EGFR phosphorylation. Berberine promotes endocytosis of activated EGFR, while as Costunolide increases ubiquitination of EGFR and reduces EGFR recycling to cell membrane distribution, thereby inhibiting EGF signaling. Berberine and Costunolide target two different steps in regulating the EGF signaling, which explains the synergistic anti-cancer effect of DHW. Since Berberine and Costunolide do not directly target EGFR phosphorylation, DHW could be a supplementary medicine to tyrosine kinase inhibitors in cancer therapy.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Fator de Crescimento Epidérmico/antagonistas & inibidores , Medicina Herbária/métodos , Neoplasias Hepáticas/tratamento farmacológico , Medicina Tradicional do Leste Asiático/métodos , Apoptose/efeitos dos fármacos , Berberina/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Mongólia , Plantas Medicinais , Sesquiterpenos/uso terapêutico
10.
Ecotoxicol Environ Saf ; 194: 110417, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32171958

RESUMO

A fluorescence aptasensor for the highly specific and sensitive determination of tetrodotoxin was established with tetrodotoxin-aptamer as the recognition unit, berberine as the signal reporter and exonuclease I as the elimination agent for the background. Berberine has a weak fluorescence emission at 540 nm, and it can form the tetrodotoxin-aptamer/berberine complex, resulted in an increased fluorescence. After introducing exonuclease I, it can degrade the single strand oligonucleotides of tetrodotoxin-aptamer into the single nucleotide in the absence of tetrodotoxin, which lead to dramatic fluorescence quenching, and reduce the background signal of sensing system. Once tetrodotoxin is in the presence, tetrodotoxin-aptamer is converted into the stable neck ring conformation, which resists the degradation of exonuclease I and provides a more rigid micro-environment for the excited state of berberine, and then the strong fluorescence is observed. Based on the above properties, an ultrasensitive label-free fluorescence aptasensor for tetrodotoxin is established. The fluorescence aptasensor shows good analytical performance with the linear increase of fluorescence intensity at the tetrodotoxin concentration from 0.030 nM to 6.0 × 103 nM. The detection limit of 11.0 pM is much lower than that of other reported sensor methods.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Exodesoxirribonucleases/química , Fluorometria/métodos , Tetrodotoxina/análise , Animais , Berberina/química , Humanos , Limite de Detecção , Músculos/química , Tetraodontiformes , Tetrodotoxina/sangue
11.
Nucleic Acids Res ; 48(8): 4179-4194, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32182342

RESUMO

Abnormal DUX4 expression in skeletal muscles plays a key role in facioscapulohumeral muscular dystrophy (FSHD) pathogenesis, although the molecular mechanisms regulating DUX4 expression are not fully defined. Using bioinformatic analysis of the genomic DUX4 locus, we have identified a number of putative G-quadruplexes (GQs) forming sequences. Their presence was confirmed in synthetic oligonucleotiode sequences derived from the enhancer, promoter and transcript of DUX4 through circular dichroism and nuclear magnetic resonance analysis. We further examined the binding affinity of a naturally occurring GQ stabilizing compound, berberine, to these non-canonical genetic structures using UV-Vis and fluorescence spectroscopy. Subsequent in vitro study in FSHD patient myoblasts indicated that berberine treatment reduced DUX4 expression and also expression of genes normally switched on by DUX4. Further investigation in a mouse model overexpressing exogenous DUX4 confirmed the therapeutic effects of berberine in downregulating DUX4 protein expression, inhibiting muscle fibrosis, and consequently rescuing muscle function. Our data demonstrate for the first time that GQs are present in the DUX4 locus and that the GQ interactive ligand reduces DUX4 expression suggesting potential role of GQs in FSHD pathogenesis. Our work provides the basis of a novel therapeutic strategy for the treatment of FSHD.


Assuntos
Quadruplex G , Proteínas de Homeodomínio/genética , Distrofia Muscular Facioescapuloumeral/genética , Animais , Berberina/química , Berberina/farmacologia , Fusão Celular , Linhagem Celular Tumoral , Células Clonais , Regulação para Baixo , Elementos Facilitadores Genéticos , Fibrose , Proteínas de Homeodomínio/metabolismo , Ligantes , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Músculo Esquelético/fisiologia , Distrofia Muscular Facioescapuloumeral/metabolismo , Mioblastos/fisiologia , Motivos de Nucleotídeos , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-32145638

RESUMO

Berberidis cortex, the dry bark of Berberis L., is used to treat diabetes and contains at least three bioactive components: berberine (BBR), berbamine (BBM) and magnoflorine (MGF). BBR in turn is metabolized into berberrubine (BRB). Although it is possible to quantify each of these components individually in serum, there are currently no methods for simultaneously quantifying all four. Here, we developed a specific and rapid method for simultaneously quantifying BBR, BBM, MGF and BRB in mouse serum using ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples were pretreated by protein precipitation, separated using an ACQUITY UPLC® BEH C18 column and detected by a triple quadrupole mass spectrometer with electrospray ionization. The compound [9,10-(OC2H3)2]-BBR (d6-BBR) was used as internal standard for BBR and BRB, boldine (BOL) for MGF and tetrandrine (TET) for BBM. The m/z transitions for precursor/product ion pairs were 336.1/320.2 for BBR, 305.2/566.3 for BBM, 342.0/297.1 for MGF, 322.1/307.2 for BRB, 342.2/294.3 for d6-BBR, 312.2/580.3 for TET and 328.1/265.2 for BOL. We validated our method in terms of selectivity, linearity and lower limit of quantification, accuracy, precision, matrix effect and recovery, dilution integrity and stability. This method showed good linearity from 0.1 to 40 ng/mL for BBR, 8 to 3200 ng/mL for BBM, 5 to 2000 ng/mL for MGF and 0.2 to 80 ng/mL for BRB. The chromatographic run time was 3.9 min, and sample preparation took approximately 15 min per batch. Finally, we used our method to measure BBR, BBM, MGF and BRB in serum from diabetic mice after gavage administration of BBR hydrochloride, BBM hydrochloride, and MGF. This method is precise, accurate and suitable for high-throughput sample analysis.


Assuntos
Anti-Inflamatórios não Esteroides/sangue , Aporfinas/sangue , Benzilisoquinolinas/sangue , Berberina/sangue , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Aporfinas/análise , Aporfinas/metabolismo , Benzilisoquinolinas/análise , Benzilisoquinolinas/metabolismo , Berberina/análogos & derivados , Berberina/metabolismo , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental , Limite de Detecção , Camundongos , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
13.
Zhonghua Yan Ke Za Zhi ; 56(2): 131-137, 2020 Feb 11.
Artigo em Chinês | MEDLINE | ID: mdl-32074824

RESUMO

Objective: To study the safety of topical berberine solution in rabbit eyes and its effect on corneal epithelial repair in rabbit eyes. Methods: Experimental Study. Ninety-two Japanese rabbits were randomly divided into two groups by random number table method: the general group (32 rabbits, 64 eyes) and the corneal injury group (60 rabbits, 60 eyes).The general groups were further divided into 4 groups by random number table method, and each group has 8 rabbits (16 eyes). According to the administration of deionized water or 0.5, 1.0, 1.5 mg/ml berberine solution, they were divided into the general control group and the general A, B, and C group. Dosing with both eyes, each eye was given a single dose, and then it was given multiple times for 4 weeks after observation for 72h. After the corneal epithelium injury model made in the right eye of rabbits in the corneal injury groups, they were divided into a corneal injury control group and a corneal injury group A, B, and C according to the administration of deionized water or 0.5, 1.0, 1.5 mg/ml berberine solution. there were 5 rabbits (15 eyes) in each group, and the solutions were given continuously for 1 week. The rabbits in the general group were observed their behavioral changes, ocular surface and iris were scored by Draize eye irritation test scoring system. IOP was measured at different time points. Electroretinogram (ERG) was used to detect b-wave amplitude. In the corneal injury group, corneal epithelial defect repairment was observed at 1, 2, 3, 4, 5, 6, and 7 days after the corneal defect. Corneal histopathology observation after discontinuation of all rabbits. The pH value of rabbit tears was described by the paired t test, and the score of Draize eye irritation test were described by the rank-sum test. The analysis of variance and SNK-q were used for IOP, electroretinogram b-wave amplitude, corneal epithelial injury area and repair time. Results: No abnormal behavior was observed in the general group rabbits after single and multiple administration. There was no significant difference in the Draize eye irritation score among the general control group and the general group A, B, C at 1, 2, and 4 weeks of multiple administrations. Among them, the Draize eye irritation score of the general group C was 7 (0, 12), 6 (0, 10), 6 (0, 16) points (χ(2)=1.640, 0.265, 1.963, 1.381; P>0.05).There were no significant difference in IOP at different times among the general control group and the general group A, B, C at different times (F=0.065, 0.292, 0.015, 0.041; P>0.05). Before multiple administrations and after administration at 2, 4 weeks, the b-wave amplitudes of the general control group were (127.75±17.12), (129.18±15.83), (128.81±13.58) µV, and the general group A were (130.68).±18.75), (131.38±16.96), (130.62±12.18) µV,and the general group B were (128.00±16.74), (128.44±16.64), (129.06±16.16) µV, and the general group C were (131.81±19.37), (132.13±18.36), (129.94±12.60) µV. There was no statistically significant difference in b-wave amplitude in the groups at different times before and after administration (F=0.037, 0.011, 0.017, 0.702; P>0.05). There was no significant difference in the results of corneal histopathology among the general control group and the general group A, B, C. The area of corneal epithelial defect in each corneal injury group was statistically significant at different time (F=5.316, 25.864, 127.613; P<0.05). The corneal injury control group compared with the corneal injury group A, B, C, the corneal epithelial defect area in the corneal injury group C was significantly larger than the other three groups, with statistical differences (q=5.153, 10.313, 6.976; P<0.05). The repair time of corneal epithelial in control group and the group A,B,C of corneal injury were (83.0±1.85), (82.9±2.07), (83.7±2.09) and (101.6±2.20) h. The corneal epithelium defect repair time in group C was longer and the difference was statistically significant (F=301.437, P=0.000). Comparing the corneal injury control group and corneal injury group A and B, there was no statistical difference in the repair time of corneal epithelial defect (F=0.813, P=0.450). After repair, there was no significant difference in the pathological results of the corneal tissue between the corneal injury groups. Conclusions: Berberine solution in rabbit eyes with topical application was safety, and has no obvious toxic effect on the ocular surface and ERG of normal rabbits. 1.5 mg/ml berberine solution delayed the repair of experimental corneal epithelial defect, but had no effect on the integrity of corneal tissue after repair. (Chin J Ophthalmol, 2020, 56: 131-137).


Assuntos
Antifúngicos , Berberina , Córnea , Administração Tópica , Animais , Antifúngicos/administração & dosagem , Berberina/administração & dosagem , Córnea/efeitos dos fármacos , Córnea/patologia , Eletrorretinografia , Coelhos
14.
Arch Gynecol Obstet ; 301(1): 53-60, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32060683

RESUMO

PURPOSE: The therapy of polycystic ovary syndrome (PCOS) is based on synthetic hormones associated with lifestyle changes, but these therapies cannot be taken continuously, especially by women who would like to become pregnant. Thus, nutraceutical compounds were investigated as possible agents for treatment of PCOS. Berberine is shown to be effective against insulin resistance and obesity, particularly against visceral adipose tissue (VAT). Because of these properties, researchers theorized that berberine could be effective in PCOS treatment. METHODS: The aim of this narrative review was to assess the state of the art about the use of berberine in PCOS management. RESULTS: This review included 5 eligible studies. Despite the number of studies considered being low, the number of women studied is high (1078) and the results are interesting. Two authors find out that berberine induced a redistribution of adipose tissue, reducing VAT in the absence of weight loss and improved insulin sensitivity, quite like metformin. One author demonstrated that berberine improved the lipid pattern. Moreover, three authors demonstrated that berberine improved insulin resistance in theca cells with an improvement of the ovulation rate per cycle, so berberine is also effective on fertility and live birth rates. CONCLUSIONS: Finally, berberine is safe to use in premenopausal women who want to get pregnant and showed few side effects in all the cited studies. In conclusion, the use of berberine for PCOS is safe and promising, even if more studies are needed to create a consensus about the dosage of berberine useful for long-term therapy.


Assuntos
Berberina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Berberina/farmacologia , Feminino , Humanos , Gravidez
15.
Life Sci ; 247: 117442, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32081663

RESUMO

Transient receptor potential vanilloid type 1 (TRPV1) channels are emerging therapeutic targets for metabolic disorders. Berberine, which is a modulator of TRPV1, has proven antiobesity and antidiabetic potentials. The present study was aimed to investigate the protective effects of berberine in olanzapine-induced alterations in hypothalamic appetite control, inflammation and metabolic aberrations in mice targeting TRPV1 channels. Female BALB/c mice (18-23 g) were treated with olanzapine (6 mg/kg, p.o.) for six weeks to induce metabolic alterations, while berberine (100 and 200 mg/kg, p.o.) and metformin (100 mg/kg, p.o) were used as test and standard interventions respectively. Weekly assessment of feed-water intake, body temperature and body weight was done, while locomotion was measured at the end of week 1 and 6. Serum glucose and lipid profile were assessed by biochemical methods, while other serum biomarkers were assessed by ELISA. qPCR was used to quantify the mRNA expression in the hypothalamus. Olanzapine treatment significantly increased the feed intake, weight gain, adiposity index, while reduced body temperature and locomotor activity which were reversed by berberine treatment. Berberine treatment reduced serum ghrelin and leptin levels as well decrease in hypothalamic mRNA expression of orexigenic neuropeptides, inflammatory markers and ghrelin receptor in olanzapine-treated mice. Olanzapine treatment increased expression of TRPV1/TRPV3 in the hypothalamus which was significantly decreased by berberine treatment. Our results suggest that berberine, by TRPV1/TRPV3 modulation, attenuated the olanzapine-induced metabolic alterations in mice. Hence berberine supplementation in psychiatric patients could be a preventive approach to reduce the metabolic adverse effects of antipsychotics.


Assuntos
Antipsicóticos/uso terapêutico , Berberina/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Olanzapina/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Antipsicóticos/efeitos adversos , Berberina/efeitos adversos , Temperatura Corporal , Peso Corporal , Citocinas/metabolismo , Ingestão de Líquidos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Grelina/sangue , Grelina/metabolismo , Hipotálamo/metabolismo , Leptina/sangue , Leptina/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Terapia de Alvo Molecular/métodos , Neuropeptídeos/metabolismo , Obesidade , RNA Mensageiro , Transdução de Sinais , Canais de Cátion TRPV/genética , Resultado do Tratamento
16.
Life Sci ; 248: 117456, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097666

RESUMO

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Fatores Reguladores de Interferon/genética , Interferon gama/genética , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/antagonistas & inibidores , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Quimiocina CXCL9/antagonistas & inibidores , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Doença Crônica , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Gastrite Atrófica/genética , Gastrite Atrófica/imunologia , Gastrite Atrófica/microbiologia , Regulação da Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Humanos , Fatores Reguladores de Interferon/antagonistas & inibidores , Fatores Reguladores de Interferon/imunologia , Interferon gama/antagonistas & inibidores , Interferon gama/imunologia , Interleucina-17/agonistas , Interleucina-17/genética , Interleucina-17/imunologia , Masculino , Proteínas NLR/antagonistas & inibidores , Proteínas NLR/genética , Proteínas NLR/imunologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Uridina Fosforilase/antagonistas & inibidores , Uridina Fosforilase/genética , Uridina Fosforilase/imunologia
17.
BMC Complement Med Ther ; 20(1): 61, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087732

RESUMO

BACKGROUND: Pharmacokinetic interaction is one of the most important indices for the evaluation of the compatibility of herbal medicines. Both Gancao (Glycyrrhizae Radix et Rhizoma) and Huanglian (Coptidis Rhizoma) are commonly used traditional Chinese medicines (TCMs). In this study, the influence of Gancao on the pharmacokinetics of Huanglian was systematically studied by using berberine as a pharmacokinetic marker. METHODS: Extracts of the herbal pieces of Huanglian and the herb pair (Huanglian plus Gancao) were prepared with boiling water. The concentration of berberine in the samples was analyzed using liquid chromatography-mass spectrometry. The total amounts of berberine in all extract samples were compared. Comparative pharmacokinetic studies of Huanglian and the herb pair were conducted in ICR mice. In vitro berberine absorption and efflux were studied using mice gut sacs. The equilibrium solubility of berberine in the extracts was determined. The in vitro dissolution of berberine was comparatively studied using a rotating basket method. RESULTS: Gancao significantly reduced berberine exposure in the portal circulation (425.8 ng·h/mL vs. 270.4 ng·h/mL) and the liver (29,500.8 ng·h/mL vs. 15,422.4 ng·h/mL) of the mice. In addition, Gancao decreased the peak concentration (Cmax) of berberine in the portal circulation (104.3 ng·h/mL vs. 76.5 ng·h/mL) and liver (4926.1 ng·h/mL vs. 2642.8 ng·h/mL) of mice. Significant influences of Gancao on the amount of berberine extracted (32% reduction), the solubility of berberine (34.7% compared with the control group), and dissolution (88.7% vs. 66.1% at 15 min in acid buffer and 68% vs. 51.8% at 15 min in phosphate buffer) were also revealed. Comparative pharmacokinetic studies in ICR mice indicated that the formation of sediment was unfavorable in terms of berberine absorption (345.3 ng·h/mL vs. 119.8 ng·h/mL). CONCLUSIONS: Gancao was able to reduce intestinal absorption and in vivo exposure of berberine in Huanglian via the formation of sediment, which caused reductions in the extracted amount, solubility, and dissolution of berberine.


Assuntos
Berberina/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Extratos Vegetais/farmacocinética , Animais , Cromatografia Líquida , Quimioterapia Combinada , Feminino , Masculino , Espectrometria de Massas , Medicina Tradicional Chinesa , Camundongos Endogâmicos ICR , Raízes de Plantas
18.
Chem Biol Interact ; 317: 108947, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31968208

RESUMO

Inflammatory responses play a remarkable role in the mechanisms of acute and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and lung cancer. Currently, there is a resurgence in the use of drugs from natural sources for various ailments as potent therapeutics. Berberine, an alkaloid prominent in the Chinese traditional system of medicine has been reported to exert therapeutic properties in various diseases. Nevertheless, the number of studies focusing on the curative potential of berberine in inflammatory diseases involving the respiratory system is limited. In this review, we have attempted to discuss the reported anti-inflammatory properties of berberine that function through several pathways such as, the NF-κB, ERK1/2 and p38 MAPK pathways which affect several pro-inflammatory cytokines in the pathophysiological processes involved in chronic respiratory diseases. This review would serve to provide valuable information to researchers who work in this field and a new direction in the field of drug discovery with respect to respiratory diseases.


Assuntos
Berberina/farmacologia , Inflamação/tratamento farmacológico , Doenças Respiratórias/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Doença Crônica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos
19.
Lancet Gastroenterol Hepatol ; 5(3): 267-275, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31926918

RESUMO

BACKGROUND: Chemoprevention of colorectal adenoma and colorectal cancer remains an important public health goal. The present study aimed to investigate the clinical potential and safety of berberine for prevention of colorectal adenoma recurrence. METHODS: This double-blind, randomised, placebo-controlled trial was done in seven hospital centres across six provinces in China. Individuals aged 18-75 years who had at least one but no more than six histologically confirmed colorectal adenomas that had undergone complete polypectomy within the 6 months before recruitment were recruited and randomly assigned (1:1) to receive berberine (0·3 g twice daily) or placebo tablets via block randomisation (block size of six). Participants were to undergo a first follow-up colonoscopy 1 year after enrolment, and if no colorectal adenomas were detected, a second follow-up colonoscopy at 2 years was planned. The study continued until the last enrolled participant reached the 2-year follow-up point. All participants, investigators, endoscopists, and pathologists were blinded to treatment assignment. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. Analysis was based on modified intention-to-treat, with the full analysis set including all randomised participants who received at least one dose of study medication and who had available efficacy data. The study is registered with ClinicalTrials.gov, number NCT02226185; the trial has ended and this report represents the final analysis. FINDINGS: Between Nov 14, 2014, and Dec 30, 2016, 553 participants were randomly assigned to the berberine group and 555 to the placebo group. The full analysis set consisted of 429 participants in the berberine group and 462 in the placebo group. 155 (36%) participants in the berberine group and 216 (47%) in the placebo group were found to have recurrent adenoma during follow-up (unadjusted relative risk ratio for recurrence 0·77, 95% CI 0·66-0·91; p=0·001). No colorectal cancers were detected during follow-up. The most common adverse event was constipation (six [1%] of 446 patients in the berberine group vs one [<0·5%] of 478 in the placebo group). No serious adverse events were reported. INTERPRETATION: Berberine 0·3 g twice daily was safe and effective in reducing the risk of recurrence of colorectal adenoma and could be an option for chemoprevention after polypectomy. FUNDING: National Natural Science Foundation of China.


Assuntos
Adenoma/prevenção & controle , Antineoplásicos Fitogênicos/uso terapêutico , Berberina/uso terapêutico , Neoplasias Colorretais/patologia , Adenoma/patologia , Adenoma/cirurgia , Adolescente , Adulto , Assistência ao Convalescente , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Berberina/administração & dosagem , Berberina/efeitos adversos , Quimioprevenção/métodos , China/epidemiologia , Colonoscopia/métodos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/epidemiologia , Método Duplo-Cego , Humanos , Análise de Intenção de Tratamento/métodos , Pessoa de Meia-Idade , Placebos/administração & dosagem , Plantas Medicinais/efeitos adversos , Recidiva , Segurança , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA