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1.
Front Immunol ; 11: 802, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431711

RESUMO

Innate lymphoid cells (ILCs), including ILC1s, ILC2s, and ILC3s, play critical roles in regulating immunity, inflammation, and tissue homeostasis. However, limited attention is focused on the unique phenotype of ILCs in the heart tissue. In this study, we analyzed the ILC subsets in the heart by flow cytometry and found that ILC2s were the dominant population of ILCs, while a lower proportion of type 1 ILCs (including ILC1 and NK cells) and merely no ILC3s in the heart tissue of mice. Our results show that ILC2 development kinetically peaked in heart ILC2s at the age of 4 weeks after birth and later than lung ILC2s. By conducting parabiosis experiment, we show that heart ILC2s are tissue resident cells and minimally replaced by circulating cells. Notably, heart ILC2s have unique phenotypes, such as lower expression of ICOS, CD25 (IL-2Rα), and Ki-67, higher expression of Sca-1 and GATA3, and stronger ability to produce IL-4 and IL-13. In doxorubicin-induced myocardial necroptosis model of mouse heart tissue, IL-33 mRNA expression level and ILC2s were remarkably increased. In addition, IL-4 production by heart ILC2s, but not lung ILC2s, was also dramatically increased after doxorubicin treatment. Our results demonstrate that heart-resident ILC2s showed tissue-specific phenotypes and rapidly responded to heart injury. Thus, further studies are warranted to explore the potential for IL-33-elicited ILC2s response as therapeutics for attenuating heart damage.

2.
Nat Commun ; 9(1): 4874, 2018 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-30451838

RESUMO

The metabolic checkpoint kinase mechanistic/mammalian target of rapamycin (mTOR) regulates natural killer (NK) cell development and function, but the exact underlying mechanisms remain unclear. Here, we show, via conditional deletion of Raptor (mTORC1) or Rictor (mTORC2), that mTORC1 and mTORC2 promote NK cell maturation in a cooperative and non-redundant manner, mainly by controlling the expression of Tbx21 and Eomes. Intriguingly, mTORC1 and mTORC2 regulate cytolytic function in an opposing way, exhibiting promoting and inhibitory effects on the anti-tumor ability and metabolism, respectively. mTORC1 sustains mTORC2 activity by maintaining CD122-mediated IL-15 signaling, whereas mTORC2 represses mTORC1-modulated NK cell effector functions by restraining STAT5-mediated SLC7A5 expression. These positive and negative crosstalks between mTORC1 and mTORC2 signaling thus variegate the magnitudes and kinetics of NK cell activation, and help define a paradigm for the modulation of NK maturation and effector functions.


Assuntos
Células Matadoras Naturais/imunologia , Proteína Companheira de mTOR Insensível à Rapamicina/genética , Proteína Regulatória Associada a mTOR/genética , Proteínas com Domínio T/genética , Animais , Diferenciação Celular , Regulação da Expressão Gênica , Humanos , Interleucina-15/genética , Interleucina-15/imunologia , Subunidade beta de Receptor de Interleucina-2/genética , Subunidade beta de Receptor de Interleucina-2/imunologia , Células Matadoras Naturais/citologia , Transportador 1 de Aminoácidos Neutros Grandes/genética , Transportador 1 de Aminoácidos Neutros Grandes/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteína Companheira de mTOR Insensível à Rapamicina/deficiência , Proteína Companheira de mTOR Insensível à Rapamicina/imunologia , Proteína Regulatória Associada a mTOR/deficiência , Proteína Regulatória Associada a mTOR/imunologia , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/imunologia , Transdução de Sinais , Proteínas com Domínio T/imunologia
3.
Sci Rep ; 7(1): 4759, 2017 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-28684853

RESUMO

Recent data have shown that the expression of lysosome-associated membrane protein type 2 A (LAMP2A), the key protein in the chaperone-mediated autophagy (CMA) pathway, is elevated in breast tumor tissues. However, the exact effects and mechanisms of CMA during breast cancer metastasis remain largely unknown. In this study, we found that the LAMP2A protein level was significantly elevated in human breast cancer tissues, particularly in metastatic carcinoma. The increased LAMP2A level was also positively correlated with the histologic grade of ductal breast cancer. High LAMP2A levels also predicted shorter overall survival of breast cancer patients. Downregulation of CMA activity by LAMP2A knockdown significantly inhibited the growth and metastasis of both MDA-MB-231 and MDA-MB-468 breast cancer cells in vivo and in vitro, while upregulation of CMA activity by LAMP2A overexpression had the opposite effect. Mechanistically, we found that elevated CMA activity mediated increased growth and metastasis of human breast cancer cells by downregulating the activity of autophagy-related gene 5 (ATG5)-dependent macroautophagy. Collectively, these results indicate that the anti-macroautophagic property is a key feature of CMA-mediated tumorigenesis and metastasis and may, in some contexts, serve as an attractive target for breast cancer therapies.


Assuntos
Proteína 5 Relacionada à Autofagia/genética , Autofagia/genética , Neoplasias da Mama/genética , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Proteína 2 de Membrana Associada ao Lisossomo/genética , Animais , Proteína 5 Relacionada à Autofagia/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Metástase Linfática , Proteína 2 de Membrana Associada ao Lisossomo/antagonistas & inibidores , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Lisossomos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Gradação de Tumores , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Sci Rep ; 6: 32642, 2016 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-27616627

RESUMO

Growing evidence has demonstrated that maternal detrimental factors, including inflammation, contribute to the development of hypertension in the offspring. The current study found that offspring subjected to prenatal exposure of inflammation by lipopolysaccharide (LPS) challenge during the second semester showed significantly increased systolic blood pressure. In addition, these offspring also displayed augmented vascular damage and reactive oxygen species (ROS) levels in thoracic aortas when challenged with deoxycorticosterone acetate and high-salt diet (DOCA-salt). Interestingly, the antioxidant N-acetyl-L-cysteine markedly reversed these changes. Mechanistically, prenatal LPS exposure led to pre-existing elevated peroxisome proliferators-activated receptor-γ co-activator (PGC)-1α, a critical master of ROS metabolism, which up-regulated the ROS defense capacity and maintained the balance of ROS generation and elimination under resting state. However, continued elevation of NF-κB activity significantly suppressed the rapid recovery of PGC-1α expression response to DOCA-salt challenge in offspring that underwent prenatal inflammatory stimulation. This was further confirmed by using a NF-κB inhibitor (N-p-Tosyl-L-phenylalanine chloromethyl ketone) that restored PGC-1α recovery and prevented blood pressure elevation induced by DOCA-salt. Our results suggest that maternal inflammation programmed proneness to NF-κB over-activation which impaired PGC-1α-mediated anti-oxidant capacity resulting in the increased sensitivity of offspring to hypertensive damage.


Assuntos
Hipertensão/fisiopatologia , Inflamação/fisiopatologia , NF-kappa B/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Animais , Antioxidantes/metabolismo , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Pressão Sanguínea/genética , Desoxicorticosterona/metabolismo , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Hipertensão/induzido quimicamente , Hipertensão/complicações , Hipertensão/genética , Inflamação/induzido quimicamente , Inflamação/complicações , Inflamação/genética , Lipopolissacarídeos/toxicidade , Exposição Materna , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética
5.
Sci Rep ; 6: 30146, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27443826

RESUMO

Maternal inflammation contributes to the increased incidence of adult cardiovascular disease. The current study investigated the susceptibility of cardiac damage responding to isoproterenol (ISO) in adult offspring that underwent maternal inflammation (modeled by pregnant Sprague-Dawley rats with lipopolysaccharides (LPS) challenge). We found that 2 weeks of ISO treatment in adult offspring of LPS-treated mothers led to augmented heart damage, characterized by left-ventricular systolic dysfunction, cardiac hypertrophy and myocardial fibrosis. Mechanistically, prenatal exposure to LPS led to up-regulated expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, antioxidant enzymes, and p38 MAPK activity in left ventricular of adult offspring at resting state. ISO treatment exaggerated ROS generation, p38 MAPK activation but down-regulated reactive oxygen species (ROS) elimination capacity in the left ventricular of offspring from LPS-treated mothers, while antioxidant N-acetyl-L-cysteine (NAC) reversed these changes together with improved cardiac functions. The p38 inhibitor SB202190 alleviated the heart damage only via inhibiting the expression of NADPH oxidases. Collectively, our data demonstrated that prenatal inflammation programs pre-existed ROS activation in the heart tissue, which switches on the early process of oxidative damages on heart rapidly through a ROS-p38 MAPK-NADPH oxidase-ROS positive feedback loop in response to a myocardial hypertrophic challenge in adulthood.


Assuntos
Cardiopatias/metabolismo , Coração/fisiopatologia , Inflamação/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Antioxidantes/metabolismo , Feminino , Coração/efeitos dos fármacos , Cardiopatias/induzido quimicamente , Imidazóis/farmacologia , Inflamação/induzido quimicamente , Isoproterenol/farmacologia , Masculino , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Gravidez , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
6.
PLoS One ; 11(4): e0153434, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27073902

RESUMO

Prenatal exposure to an inflammatory stimulus has been shown to cause renal damage in offspring. Our present study explored the role of intra-renal NF-κB activation in the development of progressive renal fibrosis in offspring that underwent prenatal exposure to an inflammatory stimulus. Time-dated pregnant rats were treated with saline (control group) or 0.79 mg/kg lipopolysaccharide (LPS) through intra-peritoneal injection on gestational day 8, 10 and 12. At the age of 7 weeks, offspring from control or LPS group were treated with either tap water (Con+Ve or LPS+Ve group) or pyrollidine dithiocarbamate (PDTC, 120 mg/L), a NF-κB inhibitor, via drinking water starting (Con+PDTC or LPS+PDTC group), respectively, till the age of 20 or 68 weeks. The gross structure of kidney was assessed by hematoxylin-eosin, periodic acid-Schiff staining and Sirius red staining. The expression levels of TNF-α, IL-6, α-smooth muscle actin (α-SMA) and renin-angiotensin system (RAS) genes were determined by real time polymerase chain reaction and/or immunohistochemical staining. Our data showed that post-natal persistent PDTC administration efficiently repressed intra-renal NF-κB activation, TNF-α and IL-6 expression. Post-natal PDTC also prevented intra-renal glycogen deposition and collagenous fiber generation as evident by the reduced expression of collagen III and interstitial α-SMA in offspring of prenatal LPS exposure. Furthermore, post-natal PDTC administration reversed the intra-renal renin-angiotensin system (RAS) over-activity in offspring of prenatal LPS exposure. In conclusion, prenatal inflammatory exposure results in offspring's intra-renal NF-κB activation along with inflammation which cross-talked with excessive RAS activation that caused exacerbation of renal fibrosis and dysfunction in the offspring. Thus, early life prevention of NF-κB activation may be a potential preventive strategy for chronic renal inflammation and progressive renal damage.


Assuntos
Fibrose/prevenção & controle , Rim/efeitos dos fármacos , Lipopolissacarídeos , NF-kappa B/antagonistas & inibidores , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Pirrolidinas/farmacologia , Tiocarbamatos/farmacologia , Animais , Feminino , Fibrose/induzido quimicamente , Fibrose/metabolismo , Fibrose/patologia , Rim/metabolismo , Rim/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Pirrolidinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Tiocarbamatos/uso terapêutico
7.
Sci Rep ; 6: 21692, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26877256

RESUMO

Studies involving the use of prenatally programmed hypertension have been shown to potentially contribute to prevention of essential hypertension (EH). Our previous research has demonstrated that prenatal inflammatory stimulation leads to offspring's aortic dysfunction and hypertension in pregnant Sprague-Dawley rats challenged with lipopolysaccharide (LPS). The present study found that prenatal LPS exposure led to NF-κB dyshomeostasis from fetus to adult, which was characterized by PI3K-Akt activation mediated degradation of IκBα protein and impaired NF-κB self-negative feedback loop mediated less newly synthesis of IκBα mRNA in thoracic aortas (gestational day 20, postnatal week 7 and 16). Prenatal or postnatal exposure of the IκBα degradation inhibitor, pyrollidine dithiocarbamate, effectively blocked NF-κB activation, endothelium dysfunction, and renin-angiotensin system (RAS) over-activity in thoracic aortas, resulting in reduced blood pressure in offspring that received prenatal exposure to LPS. Surprisingly, NF-κB dyshomeostasis and RAS over-activity were only found in thoracic aortas but not in superior mesenteric arteries. Collectively, our data demonstrate that the early life NF-κB dyshomeostasis induced by prenatal inflammatory exposure plays an essential role in the development of EH through triggering RAS over-activity. We conclude that early life NF-κB dyshomeostasis is a key predictor of EH, and thus, NF-κB inhibition represents an effective interventional strategy for EH prevention.


Assuntos
Hipertensão/fisiopatologia , Inflamação/complicações , NF-kappa B/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Sistema Renina-Angiotensina , Animais , Hipertensão Essencial , Feminino , Lipopolissacarídeos/toxicidade , Masculino , Gravidez , Ratos Sprague-Dawley
8.
Immunity ; 42(3): 457-70, 2015 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-25769609

RESUMO

Little is known about the role of negative regulators in controlling natural killer (NK) cell development and effector functions. Foxo1 is a multifunctional transcription factor of the forkhead family. Using a mouse model of conditional deletion in NK cells, we found that Foxo1 negatively controlled NK cell differentiation and function. Immature NK cells expressed abundant Foxo1 and little Tbx21 relative to mature NK cells, but these two transcription factors reversed their expression as NK cells proceeded through development. Foxo1 promoted NK cell homing to lymph nodes by upregulating CD62L expression and inhibited late-stage maturation and effector functions by repressing Tbx21 expression. Loss of Foxo1 rescued the defect in late-stage NK cell maturation in heterozygous Tbx21(+/-) mice. Collectively, our data reveal a regulatory pathway by which the negative regulator Foxo1 and the positive regulator Tbx21 play opposing roles in controlling NK cell development and effector functions.


Assuntos
Fatores de Transcrição Forkhead/imunologia , Regulação Neoplásica da Expressão Gênica , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/genética , Melanoma Experimental/genética , Neoplasias Cutâneas/genética , Proteínas com Domínio T/imunologia , Animais , Diferenciação Celular , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/genética , Heterozigoto , Células Matadoras Naturais/patologia , Selectina L/genética , Selectina L/imunologia , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Linfonodos/imunologia , Linfonodos/patologia , Depleção Linfocítica , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Knockout , Transplante de Neoplasias , Transdução de Sinais , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/secundário , Proteínas com Domínio T/genética
9.
J Sep Sci ; 35(19): 2659-64, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23001886

RESUMO

In this study, the bioactive component harpagoside and angroside C in the root of Scrophularia ningpoensis Hemsley was simultaneously separated by high-speed counter-current chromatography (HSCCC). A two-phase solvent system containing chloroform/n-butanol/methanol/water (4:1:3:2, v/v/v/v) was selected following consideration of the partition coefficient of the target compound. The crude extract (200 mg) was loaded onto a 280-mL HSCCC column and yielded 22 mg harpagoside and 31 mg angroside C with the purity of higher than 98 and 98.5%, respectively. It is feasible to isolate active compounds harpagoside and angroside C from S. ningpoensis using HSCCC.


Assuntos
Distribuição Contracorrente/métodos , Glicosídeos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Piranos/isolamento & purificação , Scrophularia/química , Glicosídeos/análise , Extratos Vegetais/análise , Raízes de Plantas/química , Piranos/análise
10.
J Ethnopharmacol ; 141(1): 228-33, 2012 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-22366676

RESUMO

AIMS: The root of Polygonatum odoratum (YuZhu), also a medicinal food has long been used for the treatment of diabetes. The objective of the study was to characterize the anti-diabetic active fractions or compounds in this herb. MATERIALS AND METHODS: Fractions with a different polarity were prepared by solvent extraction and macroporous absorptive resin (D101) column and their anti-diabetic potentials were evaluated by glucose uptake in HepG2 cells and STZ-induced diabetic rats. In addition, α-glycosidase inhibitory activities of active fractions were measured in vitro and chemical compositions including saponin, total flavonoids and total sugar in the fractions were determined. RESULTS: The n-buthanol fraction, a saponin-rich fraction obtained by partitioning the ethanol extract with n-buthanol after petroleum ether and acetic ether showed the highest anti-diabetic potential in glucose uptake in HepG2 cells followed by acetic ether fraction which was rich in flavonoids. Further fractionation the saponin-rich fraction using macroporous resin column (D101), polysaccharide, flavonoid and saponin rich fractions were obtained by elution with water, 40% and 60% ethanol, respectively and their anti-diabetic potentials proved by glucose uptake test in HepG2 cells and STZ-induced diabetic rats were in the order of saponin rich fraction>flavonoid rich fraction>polysaccharide rich fraction. Long-term therapy test (60d) in severe diabetic rats indicated that saponin-rich fraction significantly ameliorated clinical symptoms of diabetes including the elevated blood glucose, body weight loss as well as the increased food and water intake while flavonoid-rich fraction was more potential than saponin-rich fraction to increase superoxide dismutase (SOD) activity and decrease malondialdehyde (MDA) level in rat plasma. Additionally, saponin-rich fraction and flavonoid-rich fraction showed α-glycosidase inhibitory activity with IC(50) value of 2.05±0.32 and 3.92±0.65mg/ml, respectively. CONCLUSION: The results suggested that saponin in this herb was more important than flavonoid in exhibiting anti-diabetic activity and flavonoid contributed more to anti-oxidant activity in vivo.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Polygonatum , Saponinas/farmacologia , 1-Butanol/química , Alcanos/química , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Fracionamento Químico , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Relação Dose-Resposta a Droga , Etanol/química , Flavonoides/farmacologia , Glicosídeo Hidrolases/antagonistas & inibidores , Glicosídeo Hidrolases/metabolismo , Células Hep G2 , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/sangue , Fitoterapia , Plantas Medicinais , Polygonatum/química , Ratos , Ratos Sprague-Dawley , Rizoma , Saponinas/química , Saponinas/isolamento & purificação , Solventes/química , Superóxido Dismutase/sangue , Fatores de Tempo , Água/química
11.
Artigo em Inglês | MEDLINE | ID: mdl-22197606

RESUMO

It is known that the choice of solvent system for high speed counter-current chromatography separation is of utmost importance. In this study, a simple and rapid thin layer chromatograph coupling with fluorometric (TLC-F) method has been used to determine the partition coefficient of target compounds in HSCCC solvent system. Two components, 6,7-dimethoxycoumarin and 5-hydroxymethyl-2-furfural were successfully separated from purple sweet potato extracts by successive sample injection for the first time, using n-hexane-ethyl acetate-methanol-water (1:2:1:1, v/v/v/v) as the solvent system. Additionally, statistical analysis showed that there was no significant difference in partition coefficient obtained by the TLC-F method and by HPLC, which demonstrated the usefulness of TLC-F method.


Assuntos
Cromatografia em Camada Delgada/métodos , Distribuição Contracorrente/métodos , Ipomoea batatas/química , Extratos Vegetais/isolamento & purificação , Acetatos , Cumarínicos/isolamento & purificação , Furaldeído/análogos & derivados , Furaldeído/isolamento & purificação , Hexanos , Metanol , Extratos Vegetais/química , Sílica Gel , Água
12.
J Ethnopharmacol ; 137(3): 1135-42, 2011 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-21798327

RESUMO

AIMS: Traditional Chinese medicine (TCM) has been used for treating complex chronic diseases owing to their fewer side-effects, better patient tolerance and relatively less cost. The present work was carried out to study the anti-diabetic efficacy and mechanisms of 34 TCMs. MATERIALS AND METHODS: Streptozotocin (STZ)-diabetic mice were orally administrated with corresponding herbal solution once a day for 4 weeks. At the end of experiment, the level of plasma glucose, malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and the serum aldose reductase (AR) were determined, the effects of TCM extract on α-glucosidase and angiotensin-converting enzyme (ACE) in vitro were also evaluated. RESULTS: 13 out of the 34 herbs showed a statistically significant plasma glucose lowering action compared with the diabetic control group. Biochemical analysis revealed that Atractylodes macrocephala, Codonopsis pilosula, Dioscorea opposite, Flos lonicerae and Pueraria lobata may retard the progression of diabetes via reduce the blood glucose level and prevent the increase of AR activity. Other tested herbs, such as Ramulus cinnamomi, Cinnamomum cassia, and Eucommia ulmoides, showed the antidiabetic ability by either prevent the decrease in SOD activity or suppress the increase of MDA. Zymologic assay reveals that Pueraria lobata and Anemarrhena asphodeloides showed the highest inhibition against α-glucosidase and ACE respectively. Interestingly, the post-treatment glucose levels and AR activity were positively correlated with kidney/body weight of 34 herbs treated diabetic mice (p = 0.02, 0.04 respectively). CONCLUSIONS: Several potential antidiabetic herbs derived from Chinese traditional pharmacopeia such as Dioscorea opposite, Pueraria lobata, Codonopsis pilosula and Ramulus cinnamomi, have been found to exert a beneficial action on diabetes and diabetic complications via multi-mechanisms.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Hipoglicemiantes/farmacologia , Administração Oral , Aldeído Redutase/sangue , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Inibidores de Glicosídeo Hidrolases , Hipertrofia , Hipoglicemiantes/administração & dosagem , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Malondialdeído/sangue , Camundongos , Peptidil Dipeptidase A/metabolismo , Plantas Medicinais , Superóxido Dismutase/sangue , Fatores de Tempo , alfa-Glucosidases/metabolismo
13.
J Ethnopharmacol ; 136(2): 305-8, 2011 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-21570455

RESUMO

AIM OF THE STUDY: To evaluate traditionally used herb, Gynura divaricata (L.) DC (Bai Bei San Qi) as in vitro inhibitors of key enzymes involved in the pathogenesis of hyperglycemia and hypertension. We also determined the distribution of enzyme inhibitory activities in different aqueous and non-aqueous extracts. MATERIALS AND METHODS: The water extract (extract 1) from the aerial parts of Gynura divaricata (L.) was prepared first and then partitioned sequentially with n-butanol, ethyl acetate, and macroporous adsorptive resin (HPD-40) to yield extracts 2-4; the remaining water phase was named extract 5. Angiotensin-1 converting enzyme (ACE), α-amylase α-glycosidase inhibitory activities of the extracts were determined in vitro and chemical composition including total sugar, protein, flavonoid and total alkaloids in the extract were also evaluated. RESULTS: The water extract of this herb significantly inhibited (p<0.05) ACE activity (IC(50)=0.37 mg/ml) and showed a moderate potential hypoglycemic effect via in vitro α-amylase (IC(50)=1.36 mg/ml) and α-glycosidase (IC(50)=2.17 mg/ml) inhibition in dose-dependent manner. Further partitioning of the water extract (extracts 2-4) resulted in higher α-amylase inhibitory activities in extract 2 and 3. For α-glycosidase inhibition, extract 3 gave the highest inhibition. ACE inhibitory activities of the extracts were not improved by partitioning. Sugar, protein, flavonoid and alkaloid were found in water extract but only a small portion was partitioned in the n-butanol extract. However, a large portion of the flavonoids and alkaloids were found in ethyl acetate extract. CONCLUSION: The results confirmed potential empirical use of Gynura divaricata (L.) DC for the management of hyperglycemia as well as hypertension. The active compounds for inhibition of α-amylase and α-glycosidase inhibition were flavonoids and alkaloids while ACE inhibition probably resulted from synergic effects of all the herb compounds.


Assuntos
Asteraceae/química , Diabetes Mellitus Tipo 2/enzimologia , Inibidores Enzimáticos/farmacologia , Hipertensão/enzimologia , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Inibidores de Glicosídeo Hidrolases , Hipertensão/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fitoterapia , Componentes Aéreos da Planta , Extratos Vegetais/uso terapêutico , alfa-Amilases/antagonistas & inibidores
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