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1.
Drug Des Devel Ther ; 18: 781-799, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500692

RESUMO

Purpose: This study aimed to elucidate the protective mechanism of Traditional Chinese Medicine (TCM) Qifu Yixin formula (QFYXF) to improve heart failure (HF) by promoting ß-arrestin2 (ß-arr2)-mediated SERCA2a SUMOylation. Materials and Methods: The transverse aortic constriction (TAC)-induced HF mice were treated with QFYXF or carvedilol for 8 weeks. ß-arr2-KO mice and their littermate wild-type (WT) mice were used as controls. Neonatal rat cardiomyocytes (NRCMs) were used in vitro. Cardiac function was evaluated by echocardiography and serum NT-proBNP. Myocardial hypertrophy and myocardial fibrosis were assessed by histological staining. ß-arr2, SERCA2a, SUMO1, PLB and p-PLB expressions were detected by Western blotting, immunofluorescence and immunohistochemistry. SERCA2a SUMOylation was detected by Co-IP. The molecular docking method was used to predict the binding ability of the main active components of QFYXF to ß-arr2, SERCA2a, and SUMO1, and the binding degree of SERCA2a to SUMO1 protein. Results: The HF model was constructed 8 weeks after TAC. QFYXF ameliorated cardiac function, inhibiting myocardial hypertrophy and fibrosis. QFYXF promoted SERCA2a expression and SERCA2a SUMOylation. Further investigation showed that QFYXF promoted ß-arr2 expression, whereas Barbadin (ß-arr2 inhibitor) or ß-arr2-KO reduced SERCA2a SUMOylation and attenuated the protective effect of QFYXF improved HF. Molecular docking showed that the main active components of QFYXF had good binding activities with ß-arr2, SERCA2a, and SUMO1, and SERCA2a had a high binding degree with SUMO1 protein. Conclusion: QFYXF improves HF by promoting ß-arr2 mediated SERCA2a SUMOylation and increasing SERCA2a expression.


Assuntos
Insuficiência Cardíaca , Sumoilação , Ratos , Camundongos , Animais , Simulação de Acoplamento Molecular , Miócitos Cardíacos , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo
2.
Regul Toxicol Pharmacol ; 146: 105542, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38070762

RESUMO

Arctii Fructus is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is in the Chinese pharmacopoeia. Previous research showed that the total lignans from Arctii Fructus (TLAF) have pharmacological activities related to diabetes. This study evaluated the acute and chronic (26 weeks) toxicities associated with oral daily administration of TLAF in Sprague-Dawley (SD) rats. An acute-toxicity test showed that TLAF caused 10% mortality at 3,000 mg/kg × 2 (6-h interval), with toxic symptoms, such as dyspnea and tonic convulsions, indicating potential neurotoxicity. A chronic-toxicity study showed no mortality after administration. The no observed adverse-effect level was 1,800 mg/kg (approximately 54 times higher than the human clinical dose) for 26 weeks of TLAF oral administration in SD rats, with toxicity signs of excessive oral and nasal secretions and moist circumferential hair that recovered after TLAF discontinuation. In the toxicokinetic study, the two main components of TLAF, arctigenin plasma level was positively correlated with dose and tended to accumulate after multiple doses. At 1,800 mg/kg, arctiin plasma level increased and tended to accumulate after multiple doses. These results indicated that TLFA has relatively low toxicity and the potential for clinical treatment of diabetes.


Assuntos
Diabetes Mellitus , Medicamentos de Ervas Chinesas , Lignanas , Ratos , Humanos , Animais , Ratos Sprague-Dawley , Preparações Farmacêuticas , Diabetes Mellitus/tratamento farmacológico , Lignanas/toxicidade
3.
Phytochem Anal ; 33(8): 1214-1224, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36131366

RESUMO

INTRODUCTION: The total lignans from Fructus arctii (TLFA) is a mixture of a series of lignans isolated from dried ripe fruit of Arctium lappa L. We previously reported on the pharmacological activity of TLFA that is related to diabetes. An accurate and practical TLFA quantitative analysis method for utilising it needs to be established. OBJECTIVE: This study aimed to develop an effective quantitative analysis method for assessing the TLFA quality. METHODS: A total of 11 marker components were confirmed by analysing the high-performance liquid chromatography fingerprints of 24 batches of TLFA samples. The samples were prepared from TLFA and structurally identified as lappaol H, lappaol C, arctiin, arctignan D, arctignan E, matairesinol, arctignan G, isolappaol A, lappaol A, arctigenin, and lappaol F. In the quantitative analysis of multi-components by the single-marker (QAMS) method and with arctiin as an internal reference substance, the content of these lignans in TLFA was simultaneously determined according to their relative correction factors with arctiin. RESULTS: There was no significant difference between results measured by the QAMS and traditional external standard methods. Hierarchical cluster and principal component analyses were performed to evaluate 24 TLFA batches based on the contents of 10 marker components. The results revealed that QAMS method combined with chemometric analyses could accurately measure and clearly distinguish the different quality samples of TLFA. CONCLUSION: The QAMS method is a reliable and promising quality control method for TLFA. It can provide a reference for promoting quality control of complex multi-component systems, especially for traditional Chinese medicine.


Assuntos
Arctium , Medicamentos de Ervas Chinesas , Lignanas , Cromatografia Líquida de Alta Pressão/métodos , Frutas/química , Lignanas/análise , Arctium/química , Controle de Qualidade , Medicamentos de Ervas Chinesas/química
4.
J Ethnopharmacol ; 255: 112773, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32199990

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Arctii is the dried ripe fruit of Arctium lappa L. (family Asteraceae). It is a well-known Chinese Materia Medica that was included in the Chinese pharmacopoeia because of its traditional therapeutic actions, such as heat removal, detoxification, and elimination of swelling. Since ancient times Fructus Arctii has been used extensively in a number of classical drug formulas to treat type 2 diabetes mellitus. Modern pharmacological studies have shown that certain components of Fructus Arctii have multiple physiological activities on type 2 diabetes and its complications. AIM OF THE STUDY: We have reported the inhibitory effect of total lignans from Fructus Arctii (TLFA) on aldose reductase, the key enzyme in the polyol pathway, which is considered to be closely related to the onset of diabetic retinopathy (DR). The present study aimed to observe the preventive and therapeutic effects of TLFA on DR in Streptozotocin (STZ)-induced DR rats. MATERIALS AND METHODS: TLFA was prepared from Fructus Arctii and its content was determined using UV spectrophotometry. The DR model was induced by STZ in Wistar rats. For DR prevention, the animals were gavaged once daily for 9 weeks with TLFA (1.38, 0.69, and 0.35 g/kg/day) as soon as they were confirmed as diabetes models. Pathological changes to retinal tissues and the expression of vascular endothelial growth factor (VEGF) and protein kinase C (PKC) in the retina were detected after TLFA treatment. The effects of TLFA on blood glucose levels and body weight were also observed. For DR treatment, the animals were gavaged once daily for 12 weeks with TLFA (1.38 and 0.69 g/kg/day) at 3 months after they were confirmed as diabetes models. The therapeutic effect was studied using quantitative detection of blood-retina barrier (BRB) breakdown via an Evans Blue leakage assay. RESULTS: For DR prevention, after 9 weeks of TLFA administration, histopathological examination of retinal tissue showed that TLFA improved the lesions in the retina. Changes to retinal microstructures such as capillaries, ganglion cells, bipolar cells, and the membrane disk examined by electron microscopy further confirmed that TLFA has a preventive effect on retinopathy. Terminal deoxynucleotidyl Transferase-mediated dUTP nick end labeling (TUNEL) detection showed that TLFA could inhibit retinal cell apoptosis in the diabetic rats, and fasting blood glucose (FBG) levels of rats in the TLFA-treated groups decreased during the experiment. For DR treatment, after 3 months of administration, the amount of dye leakage in the TLFA-administered groups was reduced by more than 50% compared with that in the model group, which indicated that TLFA has a therapeutic effect on middle and late DR. Messenger RNA (mRNA) expression of VEGF and PKCß2 in the retina detected by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (FQ-RT-PCR) showed that TLFA could inhibit the expression of them, which was consistent with the results of immunohistochemistry (IHC). CONCLUSION: TLFA has a preventive and therapeutic effect on DR. Its mechanism of action on DR is related to inhibiting PKC activation and blocking VEGF elevation.


Assuntos
Arctium , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/prevenção & controle , Frutas , Lignanas/farmacologia , Extratos Vegetais/farmacologia , Retina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Arctium/química , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Barreira Hematorretiniana/efeitos dos fármacos , Barreira Hematorretiniana/metabolismo , Barreira Hematorretiniana/patologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/etiologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Ativação Enzimática , Frutas/química , Lignanas/isolamento & purificação , Masculino , Extratos Vegetais/isolamento & purificação , Proteína Quinase C beta/genética , Proteína Quinase C beta/metabolismo , Ratos Wistar , Retina/metabolismo , Retina/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Transdução de Sinais , Estreptozocina , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Am J Chin Med ; : 1-27, 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30284463

RESUMO

Diabetic retinopathy (DR), one of the most common microvascular complications of diabetic mellitus, is currently the main cause of adult-acquired blindness. The pathogenesis of DR is complex and the current clinical application of various treatment methods cannot completely prevent the development of this disease. Many reports have been published regarding the treatment of DR with Traditional Chinese Medicine (TCM), which has received increasing attention from medical practitioners worldwide. Studies published between 1994 and April 2017 were collected from the CNKI, VIP, Medline and Web of Science databases, as well as from Chinese traditional books and Chinese Pharmacopoeia, subsequently obtaining more than 550 studies. Thereafter, the status quo of DR treatment using TCM had been summarized according to four aspects - compound formula therapy, Chinese herbal medicine extracts and monomer therapy, integrated traditional Chinese and Western medicine therapy, and Chinese medicine external treatment. According to the literature reviewed herein, TCM has had definite effects on the prevention and treatment of DR, especially when used in combination with modern medical methods. However, the lack of a unified standard on the syndrome differentiation of DR and the lack of support of evidence-based medicine theory in clinical practice have been consistent concerns in previous research studies and needs to be addressed in subsequent studies.

6.
Phytother Res ; 32(4): 631-642, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29235180

RESUMO

Fructus Arctii (great burdock achene) is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is included in the Chinese pharmacopoeia. It has been reported that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. This study aimed to investigate antidiabetic activity and mechanism of total lignans from Fructus Arctii (TLFA) in KKAy mice, a spontaneous Type 2 diabetic rodent model that exhibits marked obesity. In this study, KKAy mice were gavaged once daily with solvents (0.5% sodium carboxymethyl cellulose), TLFA (250 and 125 mg/kg), or metformin (200 mg/kg) for 11 weeks, and C57BL/6J mice treated with saline solution (0.9%, w/v) were used as normal control. The results indicate that TLFA has dual effects of hypoglycemia and weight loss, and administration of TLFA in KKAy mice could decrease fasting blood glucose, glycated hemoglobin, and body weight; improve oral glucose tolerance; increase high density lipoprotein cholesterol; and decrease triglycerides and free fatty acid in mice serum. Its efficacy may associate with multiple mechanisms of action such as stimulation of insulin secretion, activation of phosphatidylinositol 3-kinase/protein kinase B, and adenosine-monophosphate-activated protein kinase signaling pathway, decreasing leptin.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Frutas/química , Hipoglicemia/etiologia , Hipoglicemiantes/farmacologia , Redução de Peso/efeitos dos fármacos , Animais , Diabetes Mellitus/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
7.
Planta Med ; 83(8): 676-683, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27894149

RESUMO

Cerebral ischemia can cause brain infarcts, which are difficult to recover due to poor angiogenesis. 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside is a natural polyphenol, has antioxidant and anti-inflammatory activity, and can protect from ischemic neuronal injury. However, little is known about the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside on brain microcirculation after stroke. This study aimed at investigating the influence of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside on brain lesions and angiogenesis after stroke. Sprague-Dawley rats were subjected to right middle cerebral artery occlusion and treated with vehicle, nimodipine, or different doses of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside daily beginning at 6 h post-middle cerebral artery occlusion for 14 days. The volume of cerebral infarcts, degree of neurological dysfunction, and level of microvessel density were determined longitudinally. The levels of vascular endothelial growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the brain lesions were characterized by immunohistochemistry and Western blot assays at 14 days post-middle cerebral artery occlusion. We found that 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside significantly promoted postoperative recovery in rats by minimizing the volume of cerebral infarcts and improving neurological dysfunction in a dose- and time-dependent manner. Additionally, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside significantly increased the microvessel density in the brain and upregulated CD31 expression in ischemic penumbra, relative to that in the control. Finally, treatment with 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside significantly upregulated the relative levels of vascular endothelial growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the brain lesions of rats. Therefore, these data indicated that 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside treatment promoted angiogenesis and recovery from ischemia/reperfusion-induced brain injury in rats.


Assuntos
Indutores da Angiogênese/uso terapêutico , Lesões Encefálicas/prevenção & controle , Isquemia Encefálica , Glucosídeos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Estilbenos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Angiotensina I/metabolismo , Animais , Western Blotting , Fallopia multiflora/química , Infarto da Artéria Cerebral Média , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor TIE-2/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Phytomedicine ; 22(1): 128-37, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25636881

RESUMO

We have reported the antidiabetic activity of the total lignans from Fructus arctii (TLFA) against alloxan-induced diabetes in mice and rats. In this study, arctigenic acid was found to be the main metabolite in rat plasma detected by UPLC/MS and HPLC/MS/MS after oral administration of TLFA. For the first time, its hypoglycemic activity and acute oral toxicity were evaluated in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and ICR mice respectively. GK rats were orally given arctigenic acid (50 mg/kg) twice daily before each meal for 12 weeks. The treatment reduced the elevated plasma glucose, glycosylated hemoglobin and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. We found that the hypoglycemic effect of arctigenic acid was partly due to the stimulation on insulin secretion, whereas the body weight was not affected by arctigenic acid administration in GK rats. Meanwhile, there was no observable acute toxicity of arctigenic acid treatment at the dosage of 280 mg/kg body weight daily in the acute 14-day toxicity study in mice. This study demonstrates that arctigenic acid may be the main metabolite in the rat serum after oral administration of TLFA, which showed significant hypoglycemic effect in GK rats, and low acute toxicity in ICR mice. The result prompts us that arctigenic acid is the key substance responsible for Fructus Arctii antidiabetic activity and it has a great potential to be further developed as a novel therapeutic agent for diabetes in humans.


Assuntos
Arctium/química , Diabetes Mellitus Experimental/tratamento farmacológico , Furanos/farmacologia , Hipoglicemiantes/farmacologia , Lignanas/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Frutas/química , Furanos/sangue , Glucose/metabolismo , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Lignanas/sangue , Lignanas/metabolismo , Masculino , Camundongos Endogâmicos ICR , Estrutura Molecular , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem , Testes de Toxicidade Aguda
9.
J Ethnopharmacol ; 151(1): 548-55, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24269245

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Arctii, called "Niubangzi" in China (Great burdock achene in English), is a well-known Chinese Materia Medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions. Meanwhile it has been utilized extensively in a number of classical drug formulas as a major component for the treatment of noninsulin-dependent diabetes mellitus. It has also been reported recently that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. The aim of this study was to investigate hypoglycemic activity of total lignans from Fructus Arctii (TLFA) in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and the mechanism of its hypoglycemic activity. MATERIALS AND METHODS: Male GK rats and normal Wistar rats were used in this study, GK rats fed twice daily were given TLFA (300 mg/kg) or nateglinide (50mg/kg) orally before each meal for 12 weeks. Besides common evaluation indexes of hypoglycemic activity such as blood glucose level, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters such as cholesterol (CHOL), triglycerides (TG), et al., in rat serum. The effects of TLFA on insulin secretion and pancreas tissue sections, the levels of serum glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and the α-glucosidase inhibitory activity of TLFA in vitro were investigated. RESULTS: TLFA demonstrated stable and long-lasting hypoglycemic activity in GK rats and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. Both TLFA and nateglinide controlled the glycosylated hemoglobin levels of the experimental animals very well. Stimulation of insulin secretion was proved to be one of the hypoglycemic mechanism of TLFA, promoting the release of GLP-1 should be another one, and ɑ-glucosidase inhibitory activity of TLFA also contributes to its hypoglycemic activity. In this study, we didn't found that TLFA could effect the body weight of GK rats, which was also verified by the changes of biochemical parameters of blood in experimental rats. CONCLUSION: The results of this study indicates that TLFA has significant hypoglycemic potential in GK rats, and it may be acting through stimulating insulin secretion, promoting the release of GLP-1, and decreasing intestinal absorption of glucose.


Assuntos
Arctium/química , Diabetes Mellitus/tratamento farmacológico , Frutas/química , Lignanas/farmacologia , Animais , Glicemia/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Ritmo Circadiano , Esquema de Medicação , Polipeptídeo Inibidor Gástrico/genética , Polipeptídeo Inibidor Gástrico/metabolismo , Regulação da Expressão Gênica , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Teste de Tolerância a Glucose , Insulina/sangue , Lignanas/química , Masculino , Ratos , Ratos Wistar
10.
Pharmacol Rep ; 62(5): 949-55, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21098879

RESUMO

Hyperoside (Hyp) is a flavonoid compound isolated from a folk remedy, Rhododendron ponticum L. leaves. It has been shown to have neuroprotective effects both in vivo and in vitro. However, little is known about the effects of Hyp on the neuronal apoptosis induced by glutamate. The present study showed that Hyp significantly attenuated, in a concentration-dependent manner, the apoptosis induced by the exposure of cultured neurons to NMDA. Western blot analysis revealed that Hyp antagonized the expression of excess NR2B-containing NMDA receptors; however, it had no effect on the expression of NR2A-containing NMDA receptors. Our results demonstrate that the neuroprotective effect of Hyp owes, at least partially, to its differential modulation of NR2A- and NR2B-containing NMDA receptors.


Assuntos
Apoptose/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Quercetina/análogos & derivados , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Células Cultivadas , Ácido Glutâmico/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Folhas de Planta/química , Córtex Pré-Frontal/citologia , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Rhododendron
11.
Phytother Res ; 24(3): 472-3, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19373770

RESUMO

The potent inhibitory effect of the total lignan from the plant Fructus Arctii on aldose reductase was observed, suggesting its preventive potential on diabetic complications upon long term administration.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Arctium/química , Lignanas/farmacologia , Extratos Vegetais/farmacologia , Animais , Inibidores Enzimáticos/farmacologia , Frutas/química , Ratos , Ratos Sprague-Dawley
12.
Bioeng Bugs ; 1(3): 207-12, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21326927

RESUMO

To achieve one-step separation of heavy metal ions from contaminated water, we have developed a novel bioremediation technology based on self-immobilization of the Caulobacter crescentus recombinant strain JS4022/p723-6H, which overexpresses hexahistidine peptide on the surface of the bacterial cells and serves as a whole-cell adsorbent for dissolved heavy metals. Biofilms formed by JS4022/p723-6H are effective at retaining cadmium from bacterial growth media or environmental water samples. Here we provide additional experiment data discussing the application potential of this new technology. Supplementation of calcium to the growth media produced robust JS4022/p723-6H cells by alleviating their sensitivity to chelators. After growth in the presence of 0.3% CaCl(2)·2H(2)O, double the amount of JS4022/p723-6H cells survived the treatment with 2 mM EDTA. Free cells of JS4022/p723-6H effectively sequestered 51% of the total cadmium from a Lake Erie water sample at pH 5.4, compared to 37% retrieved by the control strain. Similar levels of adsorption were observed at pH 4.2 as well. Cells of JS4022/p723-6H were tolerant of acid treatment for 90 min at pH ≥1.1 or 120 min at pH ≥2.5, which provides an avenue for the convenient regeneration of the bacterial cells metal-binding capacity with acidic solutions. Designs of possible bioreactors and an operation system are also presented.


Assuntos
Cádmio/metabolismo , Caulobacter crescentus/genética , Caulobacter crescentus/metabolismo , Biodegradação Ambiental , Caulobacter crescentus/crescimento & desenvolvimento , Engenharia Genética , Lagos/análise , Poluentes Químicos da Água/metabolismo
13.
Mol Pain ; 5: 71, 2009 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-20003379

RESUMO

The midbrain periaqueductal grey (PAG) is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA) caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp), one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.


Assuntos
Ácido Glutâmico/metabolismo , Inflamação/metabolismo , Dor Intratável/metabolismo , Substância Cinzenta Periaquedutal/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Vias Aferentes/metabolismo , Vias Aferentes/fisiopatologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Doença Crônica , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Adjuvante de Freund , Inflamação/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nociceptores/metabolismo , Técnicas de Cultura de Órgãos , Medição da Dor/métodos , Dor Intratável/fisiopatologia , Técnicas de Patch-Clamp , Substância Cinzenta Periaquedutal/fisiopatologia , Fenóis/farmacologia , Piperidinas/farmacologia , Quercetina/análogos & derivados , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley , Transmissão Sináptica/fisiologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
14.
Neuropharmacology ; 54(8): 1175-81, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18410946

RESUMO

Gentiopicroside is one of the secoiridoid compound isolated from Gentiana lutea. It exhibits analgesic activities in the mice. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission and induce glutamate NMDA NR2B receptor expression in the ACC. But little is known about Gentiopicroside on the persistent inflammatory pain and chronic pain-induced synaptic transmission changes in the ACC. The present study was undertaken to investigate its analgesic activities and central synaptic modulation to the peripheral painful inflammation. Gentiopicroside produced significant analgesic effects against persistent inflammatory pain stimuli in mice. Systemic administration of Gentiopicroside significantly reversed NR2B over-expression during the chronic phases of persistent inflammation caused by hind-paw administration of complete Freunds adjuvant (CFA) in mice. Whole-cell patch clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents in the ACC. Our findings provide strong evidence that analgesic effects of Gentiopicroside involve down-regulation of NR2B receptors in the ACC to persistent inflammatory pain.


Assuntos
Analgésicos não Narcóticos , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Inflamação/complicações , Inflamação/tratamento farmacológico , Iridoides/farmacologia , Iridoides/uso terapêutico , Dor/tratamento farmacológico , Dor/etiologia , Receptores de N-Metil-D-Aspartato/biossíntese , Animais , Western Blotting , Doença Crônica , AMP Cíclico/metabolismo , Regulação para Baixo/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Adjuvante de Freund , Ácido Glutâmico/fisiologia , Inflamação/induzido quimicamente , Glucosídeos Iridoides , Camundongos , Camundongos Endogâmicos C57BL , Dor/psicologia , Medição da Dor/efeitos dos fármacos , Técnicas de Patch-Clamp , Receptores de GABA-A/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos
15.
J Sep Sci ; 31(6-7): 1015-26, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18338405

RESUMO

In this study, metabolite profiling of five medicinal Panax herbs including Panax ginseng (Chinese ginseng), Panax notoginseng (Sanchi), Panax japonicus (Rhizoma Panacis Majoris), Panax quinquefolium L. (American ginseng), and P. ginseng (Korean ginseng) were performed using ultra-performance LC-quadrupole TOF MS (UPLC-QTOFMS) and multivariate statistical analysis technique. Principal component analysis (PCA) of the analytical data showed that the five Panax herbs could be separated into five different groups of phytochemicals. The chemical markers such as ginsenoside Rf, 20(S)-pseudoginsenoside F11, malonyl gisenoside Rb1, and gisenoside Rb2 accountable for such variations were identified through the loadings plot of PCA, and were identified tentatively by the accurate mass of TOFMS and partially verified by the available reference standards. Results from this study indicate that the proposed method is reliable for the rapid analysis of a group of metabolites present in herbal medicines and other natural products and applicable in the differentiation of complex samples that share similar chemical ingredients.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Panax/química , Panax/metabolismo , Estrutura Molecular , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Plantas Medicinais/química , Plantas Medicinais/metabolismo
16.
Phytother Res ; 22(1): 97-101, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17724763

RESUMO

The antidiabetic activity of the total lignan from the plant Fructus Arctii, used in China for the control of diabetes, was investigated in models of alloxan-induced diabetic mice and hyperglycemic-hyperlipidemic diabetic rats. The biochemical parameters studied were: blood glucose, glucose tolerance, serum insulin, serum triglycerides, total cholesterol and high density lipoprotein (HDL). Total lignan was given to mice and rats daily for 10 days at doses of 2.0, 1.0, 0.5 g/kg and 1.38, 0.69, 0.35 g/kg respectively. The alloxan-diabetic animals showed significant reductions in plasma glucose, triglycerides and total cholesterol after treatment with the total lignan from the plant Fructus Arctii and glibenclamide (used as standard) compared with the diabetic controls, while the glucose tolerance, serum insulin level and HDL-cholesterol were elevated without the risk of hypoglycemia. In conclusion, the total lignan from the plant Fructus Arctii has been proven to be a safer antidiabetic agent and might help to prevent diabetic complications. It can serve as a good adjuvant in the present armamentarium of antidiabetic drugs.


Assuntos
Arctium/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Lignanas/uso terapêutico , Aloxano , Animais , Glicemia/metabolismo , HDL-Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Hipoglicemiantes/química , Insulina/sangue , Lignanas/química , Camundongos , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar
17.
J Ethnopharmacol ; 111(3): 490-5, 2007 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-17236732

RESUMO

Pheretima (family Megascolecidae) has been documented as a potent agent for the treatment of cough and breathing difficulty in traditional Chinese medicine for nearly 2000 years. The water extract of Pheretima was separated into three fractions of the ethanolic precipitate, the alkaline fraction and the acidic fraction. Among the three fractions, the acidic fraction showed the most potent spasmolytic effects on histamine-induced contractions in isolated guinea pig tracheal rings, and the most inhibitory activities on increase of short circuit current induced by carbachol in isolated rat tracheal epitheliums with the IC50 values of 0.15 and 0.08 mg/ml, respectively. Further in vivo studies also displayed that the acidic fraction could protect experimental asthma model induced by the combination of histamine and acetylcholine chloride in guinea pigs to prolong the latent periods of asthma (P < 0.05) and significantly decrease the cough frequency caused by ammonia water in mice (P < 0.001).


Assuntos
Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Oligoquetos/química , Parassimpatolíticos/farmacologia , Traqueia/efeitos dos fármacos , Animais , Antiasmáticos/química , Antitussígenos/química , Antitussígenos/farmacologia , Asma/induzido quimicamente , Tosse/induzido quimicamente , Tosse/tratamento farmacológico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Feminino , Cobaias , Histamina , Concentração Inibidora 50 , Masculino , Materia Medica , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos ICR , Contração Muscular/efeitos dos fármacos , Parassimpatolíticos/química , Ratos , Ratos Sprague-Dawley , Traqueia/metabolismo
18.
Zhongguo Zhong Yao Za Zhi ; 31(18): 1485-8, 2006 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-17144461

RESUMO

OBJECTIVE: To investigate the induction and culture of adventitious root of Panax notoginseng. METHOD: Three ways, induction from the explants of three-year-old P. notoginseng. The explants of regenerated shoots and calluses, were used to induce adventitious roots. The effects of 2, 4-dichlorophenoxyacetic acid, indole-3-butyric acid and naphthylacetic acid on adventitious root induction were investigated respectively. The effects of four modes of separating adventitious roots from the parent tissues on culture in vitro were compared. RESULT: Adventitious roots were successfully induced by three methods, of which the young flower bud callus was the best material for the induction of adventitious root. Indole-3-butyric acid possessed the strongest potency for induction. The liquid culture system was established by continuous culture of adventitious roots together with their parent tissues before separated. CONCLUSION: The acquisition and culture in vitro in liquid culture system of adventitious roots of P. notoginseng lay a foundation for the next investigation.


Assuntos
Panax notoginseng/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/farmacologia , Plantas Medicinais/crescimento & desenvolvimento , Técnicas de Cultura de Tecidos/métodos , Ácido 2,4-Diclorofenoxiacético/farmacologia , Indóis/farmacologia , Ácidos Naftalenoacéticos/farmacologia , Panax notoginseng/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Plantas Medicinais/efeitos dos fármacos
19.
J Ethnopharmacol ; 108(3): 355-60, 2006 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-16829002

RESUMO

The protective effect of flavonoids extracted from Scutellaria baicalensis Georgi on cerebral ischemia injury has been explored in experimental animals. Scutellaria flavonoid (SF) could significantly prolong gasping time (prolonged ratio, 23.79%) and survival time after carotid artery occlusion, and decrease attenuate malondialdehyde (MDA) content in damaged brain tissues from 118.56+/-47.95 nmol/g in untreated to 199.29+/-24.24 nmol/g. SF could also increase the content of superoxide dismutase (SOD) in brain tissues after ischemic mice from 1486+/-94 NU/g in untreated to 1168+/-76 NU/g, and showed significant protective effect on cerebral hypoxia and reperfusion brain tissues in middle cerebral artery occlusion (MCAO) procedure. Additionally, SF has inhibitory effect on platelet aggregation, with the average inhibition rate of 45.52%, while the aspirin group was 54.96%. These results suggest that SF has a significant protective effect on cerebral ischemia and ischemia-reperfusion induced brain injury.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Flavonoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Scutellaria baicalensis/química , Animais , Arteriopatias Oclusivas/tratamento farmacológico , Arteriopatias Oclusivas/metabolismo , Isquemia Encefálica/metabolismo , Relação Dose-Resposta a Droga , Flavonoides/química , Masculino , Malondialdeído/metabolismo , Camundongos , Fármacos Neuroprotetores/química , Oxirredução/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Coelhos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
20.
Zhongguo Zhong Yao Za Zhi ; 31(3): 236-9, 2006 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-16573007

RESUMO

OBJECTIVE: To study the proportion and mechanism of relieving asthma of drug partnership comprising herbal Ephedrae & Pheretima. METHOD: To study relaxant effect on 10 micromol x L(-1) carbachol (CCh) and 10 micromol x L(-1) histamine (His) precontracted isolated tracheal rings and lowering effect on short-circuit current (Isc) increase induced by 10 micromol x L(-1) CCh with 3 proportions of 1:1, 1:3, 1:9 extract. RESULT: 1:3 proportions dose-dependently relaxed CCh-precontracted isolated tracheal rings, IC50 of 1:1, 1:3 is 7.5, 15 mg x mL(-1) respectively, 1:9 could not produce 50% inhibition effect on CCh-evoked contraction; 3 proportions also dose-dependently relaxed His-precontracted isolated tracheal rings, IC50 of 1:9, 1:3 and 1:1 is 0.19, 0.61, 1.8 mg x mL(-1) respectively. On the other hand,the orders potency of the decrease effect on CCh-evoked short circuit current increase is 1:3 > 1:1 > 1:9. The difference is not significant (P < 0.05). CONCLUSION: Herbal Ephedrae & Pheretima had tracheal muscle relaxant and epithelium ion secretion inhibition effect, its mechanism of relieving asthma involved anti-CCh and anti-His effect 1:3 was the most appropriate dosage ratio in the anti-asthmatic drug partnership.


Assuntos
Antiasmáticos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Ephedra sinica , Materia Medica/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Animais , Antiasmáticos/administração & dosagem , Asma/fisiopatologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/isolamento & purificação , Ephedra sinica/química , Cobaias , Antagonistas dos Receptores Histamínicos/farmacologia , Técnicas In Vitro , Masculino , Materia Medica/administração & dosagem , Materia Medica/isolamento & purificação , Músculo Liso/efeitos dos fármacos , Oligoquetos/química , Plantas Medicinais/química , Ratos , Ratos Sprague-Dawley
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