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1.
Chin J Nat Med ; 15(3): 178-191, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28411686

RESUMO

Heat stress can stimulate an increase in body temperature, which is correlated with increased expression of heat shock protein 70 (HSP70) and tumor necrosis factor α (TNFα). The exact mechanism underlying the HSP70 and TNFα induction is unclear. Berberine (BBR) can significantly inhibit the temperature rise caused by heat stress, but the mechanism responsible for the BBR effect on HSP70 and TNFα signaling has not been investigated. The aim of the present study was to explore the relationship between the expression of HSP70 and TNFα and the effects of BBR under heat conditions, using in vivo and in vitro models. The expression levels of HSP70 and TNFα were determined using RT-PCR and Western blotting analyses. The results showed that the levels of HSP70 and TNFα were up-regulated under heat conditions (40 °C). HSP70 acted as a chaperone to maintain TNFα homeostasis with rising the temperature, but knockdown of HSP70 could not down-regulate the level of TNFα. Furthermore, TNFα could not influence the expression of HSP70 under normal and heat conditions. BBR targeted both HSP70 and TNFα by suppressing their gene transcription, thereby decreasing body temperature under heat conditions. In conclusion, BBR has a potential to be developed as a therapeutic strategy for suppressing the thermal effects in hot environments.


Assuntos
Berberina/farmacologia , Proteínas de Choque Térmico HSP70/genética , Transtornos de Estresse por Calor/tratamento farmacológico , TATA Box/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Animais , Proteínas de Choque Térmico HSP70/metabolismo , Transtornos de Estresse por Calor/genética , Transtornos de Estresse por Calor/metabolismo , Temperatura Alta , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fator de Necrose Tumoral alfa/metabolismo
2.
Sci Rep ; 7: 45155, 2017 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-28332601

RESUMO

Transient Receptor Potential Melastatin-8 (TRPM8) reportedly plays a fundamental role in a variety of processes including cold sensation, thermoregulation, pain transduction and tumorigenesis. However, the role of TRPM8 in inflammation under cold conditions is not well known. Since cooling allows the convergence of primary injury and injury-induced inflammation, we hypothesized that the mechanism of the protective effects of cooling might be related to TRPM8. We therefore investigated the involvement of TRPM8 activation in the regulation of inflammatory cytokines. The results showed that TRPM8 expression in the mouse hypothalamus was upregulated when the ambient temperature decreased; simultaneously, tumor necrosis factor-alpha (TNFα) was downregulated. The inhibitory effect of TRPM8 on TNFα was mediated by nuclear factor kappa B (NFκB). Specifically, cold stress stimulated the expression of TRPM8, which promoted the interaction of TRPM8 and NFκB, thereby suppressing NFκB nuclear localization. This suppression consequently led to the inhibition of TNFα gene transcription. The present data suggest a possible theoretical foundation for the anti-inflammatory role of TRPM8 activation, providing an experimental basis that could contribute to the advancement of cooling therapy for trauma patients.


Assuntos
Resposta ao Choque Frio/genética , Regulação da Expressão Gênica , Canais de Cátion TRPM/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Animais , Biomarcadores , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Cálcio/metabolismo , Linhagem Celular , Humanos , Masculino , Camundongos , Camundongos Knockout , NF-kappa B/metabolismo , Transporte Proteico , RNA Interferente Pequeno/genética , Canal de Cátion TRPA1/metabolismo
3.
Sci Rep ; 7: 41712, 2017 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-28181523

RESUMO

After being studied for approximately a century, berberine (BBR) has been found to act on various targets and pathways. A great challenge in the pharmacological analysis of BBR at present is to identify which target(s) plays a decisive role. In the study described herein, a rescue experiment was designed to show the important role of mitochondria in BBR activity. A toxic dose of BBR was applied to inhibit cell proliferation and mitochondrial activity, then α-ketobutyrate (AKB), an analogue of pyruvate that serves only as an electron receptor of NADH, was proven to partially restore cell proliferation. However, mitochondrial morphology damage and TCA cycle suppression were not recovered by AKB. As the AKB just help to regenerate NAD+, which is make up for part function of mitochondrial, the recovered cell proliferation stands for the contribution of mitochondria to the activity of BBR. Our results also indicate that BBR suppresses tumour growth and reduces energy charge and mitochondrial DNA (mtDNA) copy number in a HepG2 xenograft model. In summary, our study suggests that mitochondria play an important role in BBR activity regarding tumour cell proliferation and metabolism.


Assuntos
Berberina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Butiratos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo do Ácido Cítrico/efeitos dos fármacos , DNA Mitocondrial , Relação Dose-Resposta a Droga , Dosagem de Genes , Humanos , Mitocôndrias/genética , Mitocôndrias/ultraestrutura , NAD/metabolismo , Ácido Pirúvico/metabolismo
4.
Chin J Nat Med ; 14(9): 641-652, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27667509

RESUMO

Angelica dahurica (A. dahurica) is a traditional Chinese medicinal plant being used in clinical practice. The present study demonstrated that A. dahurica could reduce white-fat weight in high-fat-diet hyperlipidemic mice, decrease total cholesterol and triglyceride concentrations in the livers of both high-fat-diet and Triton WR1339 induced hyperlipidemic mice, and enhance the total hepatic lipase activities of them. These findings were further supported by the results derived from the experiments with HepG2 cells in vitro. In addition, the proteins related to lipids metabolism were investigated using LC-MS/MS, indicating that genes of lipid metabolism and lipid transport were regulated by A. dhurica. The results from LC-MS/MS were further conformed by Western blot and real time PCR assays. A. dahurica could down-regulate the expression of catalase (CAT) and sterol carrier protein2 (SCP2) and up-regulate the expression of lipid metabolism related genes-lipase member C (LIPC) and peroxisome proliferator-activated receptor gamma (PPARγ). In the Triton WR1339 mouse liver and HepG2 cells in vitro, A. dahurica was able to increase the expression of LIPC and PPARγ, confirming the results from in vivo experiments. Imperatorin showed the same activity as A. dahurica, suggesting it was one of the major active ingredients of the herb. In conclusion, our work represented a first investigation demonstrating that A. dahurica was able to regulate lipid metabolism and could be developed as a novel approach to fighting against fatty liver and obesity.


Assuntos
Angelica/química , Medicamentos de Ervas Chinesas/administração & dosagem , Fígado Gorduroso/tratamento farmacológico , Obesidade/tratamento farmacológico , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Colesterol/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Obesidade/genética , Obesidade/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Triglicerídeos/metabolismo
5.
Chin J Nat Med ; 14(5): 354-62, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27478098

RESUMO

Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerning the influence of brazilein on the innate immunity receptors have been reported. The present study was designed to investigate the regulation of NOD2 (Nucleotide-binding oligomerization domain-containing protein 2) by brazilein for its protection of neuron in cerebral ischemia in vivo and oxygen-glucose deprivation in vitro. The results showed that brazilein could reverse the elevated expression of NOD2 and TNFα (tumor necrosis factor alpha) elicited by cerebral ischemia and reperfusion. This reduction could also be detected in normal mice and C17.2 cells, indicating that this suppressive effect of brazilein was correlated with NOD2. The results from GFP reporter plasmid assay suggested brazilein inhibited NOD2 gene transcription. In conclusion, brazilein could attenuate NOD2 and TNFα expression in cerebral ischemia and NOD2 may be one possible target of brazilein for its immune suppressive effect in neuro-inflammation.


Assuntos
Benzopiranos/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/imunologia , Medicamentos de Ervas Chinesas/administração & dosagem , Indenos/administração & dosagem , Neurônios/efeitos dos fármacos , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Células Cultivadas , Glucose/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neurônios/imunologia , Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
6.
Chin J Nat Med ; 14(6): 441-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27473962

RESUMO

Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women.


Assuntos
Benzopiranos/toxicidade , Caesalpinia/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Indenos/toxicidade , Reprodução/efeitos dos fármacos , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Gravidez
7.
Zhongguo Zhong Yao Za Zhi ; 41(12): 2362-2370, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28901086

RESUMO

A variety of pharmacological effects of berberine (BBR) are constantly being discovered with the deepening of BBR research. What followed is how to rationally use the drug according to these new pharmacological effects. Because of some cardiac toxicity and poor oral absorption, conflicts may arise between improving the bioavailability and controlling the toxicity of BBR. Meanwhile some new therapeutic uses of BBR, such as hypolipidemia, hypoglycemia as well as prevention and treatment of neurodegenerative diseases, need long-termoral administration, thereby may lead to alteration of intestinal flora and potentially affect body's other physiological functions. Based on the stated targets of BBR and related pharmaceutical properties, comprehensive analysis of these issues was conducted in this study. Some suggestions were presented below:the effect of long-term oral administration on body function, especially the intestinal flora, needs to be further investigated; risks shall be considered in changing the composition of the formulation to improve the absorption rate of oral administration; for the medication with higher concentration demand (such as anti-cancer), targeted drug-delivery is worthy to be considered.


Assuntos
Berberina/farmacologia , Administração Oral , Berberina/administração & dosagem , Disponibilidade Biológica , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos
8.
Sci Rep ; 5: 18326, 2015 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-26671652

RESUMO

Berberine (BBR) is a natural compound with variable pharmacological effects and a broad panel of target genes. We investigated berberine's pharmacological activities from the perspective of its nucleotide-binding ability and discovered that BBR directly regulates gene expression by targeting TATA boxes in transcriptional regulatory regions as well as the poly adenine (poly (A)) tail at the mRNA terminus. BBR inhibits gene transcription by binding the TATA boxes in the transcriptional regulatory region, but it promotes higher levels of expression by targeting the poly (A) tails of mRNAs. The present study demonstrates that TATA boxes and poly (A) tails are the first and second primary targets by which BBR regulates gene expression. The final outcome of gene regulation by BBR depends on the structure of the individual gene. This is the first study to reveal that TATA boxes and poly (A) tails are direct targets for BBR in its regulation of gene expression. Our findings provide a novel explanation for the complex activities of a small molecule compound in a biological system and a novel horizon for small molecule-compound pharmacological studies.


Assuntos
Regiões 3' não Traduzidas , Berberina/farmacocinética , Regulação da Expressão Gênica/efeitos dos fármacos , Poli A , Estabilidade de RNA/efeitos dos fármacos , TATA Box , Transcrição Genética/efeitos dos fármacos , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR
9.
PLoS One ; 9(6): e90850, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24603897

RESUMO

Berberine is one kind of isoquinoline alkaloid with anti-apoptotic effects on the neurons suffering ischemia. To address the explanation for these activities, the berberine-induced cell cycle arrest during neurons suffering ischemia/reperfusion had been studied in the present study. According to the in vitro neurons with oxygen-glucose deprivation and in vivo ICR mice with cerebral ischemia/reperfusion, it was found that berberine could protect the mRNA of retinoblastoma (Rb) from degradation through its function on the poly(A) tail. The prolonged half-life of retinoblastoma 1 (gene of Rb, RB1) mRNA level secures the protein level of retinoblastoma, which facilitates cell cycle arrest of neurons in the process of ischemia/reperfusion and subsequently avoids cells entering in the apoptotic process. The poly(A) tail of RB1 mRNA, as a newly identified target of berberine, could help people focus on the interaction between berberine and mRNA to further understand the biological activities and functions of berberine.


Assuntos
Berberina/farmacologia , Isquemia Encefálica/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/metabolismo , Proteína do Retinoblastoma/genética , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Sobrevivência Celular/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Camundongos Endogâmicos ICR , Células PC12 , Fosforilação , Regiões Promotoras Genéticas , Processamento de Proteína Pós-Traducional , RNA Mensageiro/genética , Ratos , Traumatismo por Reperfusão/prevenção & controle , Proteína do Retinoblastoma/metabolismo
10.
Zhongguo Zhong Yao Za Zhi ; 39(19): 3876-80, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25612458

RESUMO

Rheum franzenbachii (called Tudahuang in local) has some similarities with R. palmatum (rhubarb) collected by "China Pharmacopoeia" and is often used as a substitute of rhubarb. Can Tudahuang simply replace rhubarb in the application or whether is there difference between Tudahuang and rhubarb, and what is the difference it is important to verify the difference and understand its proper application in the field of clinical practice. In this paper, we discussed the differences of the two herbs from the views of chemistry, efficacy and toxicity based on the author's previous research work as well as literatures, by using the major role of the rhubarb "diarrhea" as the basic point. The analysis result showed that the role of diarrhea Tudahuang was much weaker than that of rhubarb. The reason lies in the difference between the contents of combined anthraquinones component. While acute toxicity in mice of Tudahuang is stronger than that of rhubarb. Thus, Tudahuang should not simply replace rhubarb in practice.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/toxicidade , Rheum/química , Animais , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Camundongos , Rheum/efeitos adversos
11.
Fitoterapia ; 91: 236-246, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24096146

RESUMO

Rhubarbs and their extractives have been used as cathartic for many years. There have been numerous breakthroughs in the pharmacological research of the drug. However, as the key point of the mechanism, the targets of the effective components still remain unclear. In this paper, with an in vitro system of isolated intestine, we found that both the rhubarb extractives and the anthraquinone derivatives can antagonize the adrenaline effectively. Furthermore, computer based docking provided the binding model of the anthraquinone derivatives and adrenergic receptor. Then, based on the results of the small intestinal promotion and purgative effect experiments in vivo, we built an "inhibitor-carrier" hypothesis to elucidate the mechanism of rhubarb. This work provided key massages for the pharmacological research of rhubarb, such a common and active medicinal plant, and might be of help for the development of new purgative drugs.


Assuntos
Antagonistas Adrenérgicos/farmacologia , Antraquinonas/farmacologia , Catárticos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Intestinos/efeitos dos fármacos , Receptores Adrenérgicos/metabolismo , Rheum/química , Portadores de Fármacos , Glucose , Mucosa Intestinal/metabolismo
12.
Eur J Pharmacol ; 708(1-3): 44-55, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23499694

RESUMO

Berberine acted as a natural medicine with multiple pharmacological activities. In the present study, we examined the effect of berberine against cerebral ischemia damage from cell cycle arrest and cell survival. Oxygen-glucose deprivation of PC12 cells and primary neurons, and carotid artery ligation in mice were used as in vitro and in vivo cerebral ischemia models. We found that the effect of berberine on cell cycle arrest during ischemia was mediated by decreased p53 and cyclin D1, increased phosphorylation of Bad (higher expression of p-Bad and higher ratio of p-Bad to Bad) and decreased cleavage of caspase 3. Meanwhile, berberine activated the PI3K/Akt pathway during the reperfusion, especially the phosphor-activation of Akt, to promote the cell survival. The neural protective effect of berberine was remained in the presence of inhibitor of mitogen-activated protein/extracellular signal-regulated kinase (MEK), but was suppressed by the inhibitors of PI3K and Akt. We demonstrated that berberine induced cell cycle arrest and cell survival to resist cerebral ischemia injury.


Assuntos
Berberina/farmacologia , Isquemia Encefálica/metabolismo , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/metabolismo , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ciclina D1/genética , Ciclina D1/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células PC12 , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
13.
PLoS One ; 8(1): e54234, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23335996

RESUMO

The purpose of this study was to assess the effects of berberine (BBR) on thermoregulation in mice exposed to hot (40°C) and cold (4°C) environmental conditions. Four groups of mice were assembled with three different dosages of BBR (0.2, 0.4, and 0.8 mg/kg) and normal saline (control). In room temperature, our largest dosage of BBR (0.8 mg/kg) can reduce rectal temperatures (Tc) of normal mice. In hot conditions, BBR can antagonize the increasing core body temperature and inhibit the expression of HSP70 and TNFα in mice; conversely, in cold conditions, BBR can antagonize the decreasing core body temperature and enhance the expression of TRPM8. This study demonstrates the dual ability of BBR in maintaining thermal balance, which is of great relevance to the regulation of HSP70, TNFα and TRPM8.


Assuntos
Berberina/farmacologia , Regulação da Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/fisiologia , Temperatura Baixa , Temperatura Alta , Animais , Berberina/administração & dosagem , Eletrocardiografia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
Chin Med J (Engl) ; 125(9): 1586-93, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22800826

RESUMO

BACKGROUND: Baicalin has a significant anti-inflammation effect and is widely used in the clinical treatment of stroke. Most of the studies of Toll-like receptor 2/4 (TLR2/4) during cerebral ischemia had defined their specific expressions in microglia in hippocampus tissue. To explore the targets of baicalin in stroke, we detected the expressions of TLR2/4 in vitro/vivo. METHODS: By constructing a cerebral ischemia-reperfusion model in vivo and glucose oxygen deprivation model, we successfully induced neuron damage, then added baicalin and detected expressions of TLR2/4, nuclear factor-kB (NF-kB), tumor necrosis factor-alpha (TNFα), and interleukin-1ß (IL-1ß) in mRNA level and protein level. RESULTS: We found distinct upregulations of TLR2/4 and TNFα in both mRNA level and protein level in PC12 cells and primary neurons. Moreover, TLR2/4 and TNFα expressions were significantly higher in mice hippocampus treated with cerebral ischemia-reperfusion. Baicalin could downregulate the expressions of TLR2/4 and TNFα in the damaged cells and mice hippocampus effectively. CONCLUSIONS: Neurons could respond to the damage and activate the related signal pathway directly. TLR2/4 responsed to the damage and sent the signal to downstream factor TNFα through activating NF-kB. Baicalin could inhibit the inflammatory reaction in neuron damage and TLR might be its targets, which explained why baicalin could widely be used in the clinical treatment of stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Flavonoides/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Isquemia Encefálica/genética , Células Cultivadas , Feminino , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/genética , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células PC12 , Ratos , Traumatismo por Reperfusão/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
J Biomed Biotechnol ; 2012: 267890, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22536016

RESUMO

This work is to study the baicalin and its three analogs, baicalin, wogonoside, and wogonin, on the protective effect of neuron from oxygen-glucose deprivation (OGD) and toll-like receptor 2 (TLR2) expression in OGD damage. The results showed that baicalin and its three analogs did protect neurons from OGD damage and downregulated protein level of TLR2. D-Glucopyranosiduronic acid on site 7 in the structure played a core of cytotoxicity of these flavonoid analogs. The methoxyl group on carbon 8 of the structure had the relation with TLR2 protein expression, as well as the anti-inflammation. In addition, we detected caspase3 and antioxidation capability, to investigate the effect of four analogs on cell apoptosis and total antioxidation competence in OGD model.


Assuntos
Flavonoides/farmacologia , Glucose/metabolismo , Neurônios/efeitos dos fármacos , Oxigênio/metabolismo , Receptor 2 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Antioxidantes/farmacologia , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Flavanonas/farmacologia , Glucosídeos/farmacologia , Imunidade Inata/fisiologia , Neurônios/metabolismo , Células PC12 , Ratos , Receptor 2 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/imunologia
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