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1.
Fitoterapia ; 175: 105915, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38508499

RESUMO

Four undescribed ginkgolides, including two rare sesquiterpene ginkgolides (compounds 1 and 2) and two diterpenoid ginkgolides (compounds 3 and 4), were isolated from Ginkgo biloba L. The structures of these four ginkgolides were identified based on extensive spectroscopic analysis, DP4+ probability analysis and X-ray diffraction. Compounds 1 and 2 exhibited excellent antiplatelet aggregation activities with IC50 values of 1.20 ± 0.25 and 4.11 ± 0.34 µM, respectively.


Assuntos
Ginkgo biloba , Ginkgolídeos , Compostos Fitoquímicos , Inibidores da Agregação Plaquetária , Ginkgo biloba/química , Estrutura Molecular , Ginkgolídeos/farmacologia , Ginkgolídeos/isolamento & purificação , Ginkgolídeos/química , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/isolamento & purificação , Inibidores da Agregação Plaquetária/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Animais , Agregação Plaquetária/efeitos dos fármacos
2.
J Ethnopharmacol ; 294: 115392, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35589019

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Justicia procumbens L. is a traditional Chinese medicine, first recorded in "Shen Nong's Herbal Classic", for the treatment of lumbar pain and fever. As a widely distributed herb, it has also been documented in India, Nepal, and Malaysia. In "Tang Materia Medica", a famous medicinal book of Tang Dynasty in ancient China, it was first used to treat diseases associated with blood stasis. Blood stasis syndrome is closely related to thrombus formation and platelet aggregation. Although some compounds isolated from this plant have anti-platelet aggregation effects, the main chemical components and mechanism of J. procumbens in terms of these effects are little known. AIMS OF THE STUDY: Through in vivo and in vitro experiments, this studsy revealed the characteristic components and action mechanism of anti-platelet aggregation by J. procumbens from an overall perspective. MATERIALS AND METHODS: The effective crude extracts of the whole plant were screened via an in vitro anti-platelet aggregation test. After incubating these extracts with apheresis platelets, high affinity compounds were detected by HPLC-MS and regulatory genes were detected using gene chips. The effective components and potential target proteins were analyzed using computational docking technology. Furthermore, the compound with the strongest predicted activity was evaluated in vivo via an anti-thrombotic test. RESULTS: Integrin aⅡbß3, PKCα, PI3Kγ, and mitogen-activated protein kinase 14 were found to be potential targets. Justicidin B, tuberculatin, chinensinaphthol methyl ether, and neojusticin B were effective compounds that inhibited human platelet aggregation by suppressing Gq-PLC-PKC and Gi-PI3K-MAPK signaling pathways. Among the compounds that bind to platelets, justicidin B showed the strongest virtual binding force. The test of carotid artery thrombosis induced by ferric chloride in SD rats confirmed that justicidin B inhibited thrombus formation. CONCLUSION: Experimental investigation showed that arylnaphthalene lignan aglycones with one methylenedioxy group and two methoxy groups are effective components for anti-platelet aggregation by J. procumbens. These compounds inhibit Gq-PLC-PKC and Gi-PI3K-MAPK signaling pathways by suppressing the expression of genes such as ITGB3, PRKCA, PIK3CG, and MAPK14. These results reflected the characteristics of multi-component and multi-target synergistic treatment of Chinese medicine.


Assuntos
Justicia , Animais , Cromatografia Líquida de Alta Pressão/métodos , Justicia/química , Fosfatidilinositol 3-Quinases , Agregação Plaquetária , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Ratos , Ratos Sprague-Dawley
3.
Molecules ; 26(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34361671

RESUMO

Aporphines, a major group of aporphinoid alkaloids, exhibit interesting and diverse pharmacological activities. A set of dimeric aporphines with an aryloxy group at C8, C9, and C11 have been isolated from six genera and shown to elicit various biological activities such as antitumor, antimalarial, antimicrobial, antiplatelet aggregation, antifibrotic, immunosuppressive, and vasorelaxant properties. In this review, the nomenclature, chemical structures, botanical sources, pharmacological activities, and synthetic approaches of this set of dimeric alkaloids are presented.


Assuntos
Anti-Infecciosos/química , Antineoplásicos/química , Aporfinas/química , Dimerização , Imunossupressores/química , Extratos Vegetais/química , Inibidores da Agregação Plaquetária/química , Vasodilatadores/química , Carbono/química , Estrutura Molecular , Plantas/química
4.
Oxid Med Cell Longev ; 2021: 2195902, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447485

RESUMO

Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. The development of these diseases has a specific factor-alteration in blood platelet activation. It has been shown that phenolic compounds have antiplatelet aggregation abilities and a positive impact in the management of CVD, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects. Thus, this review is intended to address the antiplatelet activity of phenolic compounds with special emphasis in preventing CVD, along with the mechanisms of action through which they are able to prevent and treat CVD. In vitro and in vivo studies have shown beneficial effects of phenolic compound-rich plant extracts and isolated compounds against CVD, despite that the scientific literature available on the antiplatelet aggregation ability of phenolic compounds in vivo is scarce. Thus, despite the current advances, further studies are needed to confirm the cardioprotective potential of phenolic compounds towards their use alone or in combination with conventional drugs for effective therapeutic interventions.


Assuntos
Doenças Cardiovasculares , Fenóis , Compostos Fitoquímicos , Inibidores da Agregação Plaquetária , Agregação Plaquetária/efeitos dos fármacos , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Humanos , Fenóis/química , Fenóis/uso terapêutico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/uso terapêutico
5.
PLoS One ; 16(4): e0250852, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33909702

RESUMO

Aristotelia chilensis (Mol.) Stuntz, also known as maqui, is a plant native to Chile without chemical characterization and quantification of the bioactive compounds present in it. HPLC-UV and HPLC-MS/MS studies have shown the presence, at different concentrations, of phenolic and anthocyanin compounds in fruit and leave extracts of the domesticated maqui clones Luna Nueva, Morena, and Perla Negra. The extracts from leaves and unripe fruits of Luna Nueva and Morena clones significantly inhibit platelet aggregation induced by several agonists; the extracts inhibit platelet granule secretion by decreasing the exposure of P-selectin and CD63 at the platelet membrane. Reactive oxygen species formation in platelets is lower in the presence of maqui extracts. Statistical Pearson analysis supports the levels of phenolic and anthocyanin compounds being responsible for the antiaggregant maqui effects. This work is the first evidence of antiplatelet activity from Aristotelia chilensis giving added value to the use of leaves and unripe fruits from this species.


Assuntos
Antocianinas/farmacologia , Elaeocarpaceae/química , Inibidores da Agregação Plaquetária/farmacologia , Polifenóis/farmacologia , Antocianinas/química , Antocianinas/isolamento & purificação , Chile , Cromatografia Líquida de Alta Pressão , Domesticação , Frutas/química , Humanos , Selectina-P/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/isolamento & purificação , Polifenóis/química , Polifenóis/isolamento & purificação , Espectrometria de Massas em Tandem , Tetraspanina 30/metabolismo
6.
Eur J Med Chem ; 220: 113471, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-33930801

RESUMO

Natural products have long been an important source for discovery of new drugs to treat human diseases. Piperlongumine (PL) is an amide alkaloid isolated from Piper longum L. (long piper) and other piper plants and has received widespread attention because of its diverse biological activities. A large number of PL derivatives have been designed, synthesized and assessed in many pharmacological functions, including antiplatelet aggregation, neuroprotective activities, anti-diabetic activities, anti-inflammatory activities, anti-senolytic activities, immune activities, and antitumor activities. Among them, the anti-tumor effects and application of PL and its derivatives are most extensively studied. We herein summarize the development of PL derivatives, the structure and activity relationships (SARs), and their therapeutic potential on the treatments of various diseases, especially against cancer. We also discussed the challenges and future directions associated with PL and its derivatives in these indications.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Dioxolanos/farmacologia , Hipoglicemiantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Dioxolanos/química , Dioxolanos/isolamento & purificação , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Piper/química , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/isolamento & purificação
7.
Molecules ; 26(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375091

RESUMO

Coffee is rich in caffeine (CF), chlorogenic acid (CGA) and phenolics. Differing types of coffee beverages and brewing procedures may result in differences in total phenolic contents (TPC) and biological activities. Inflammation and increases of platelet activation and aggregation can lead to thrombosis. We focused on determining the chemical composition, antioxidant activity and inhibitory effects on agonist-induced platelet aggregation and cyclooxygenase (COX) of coffee beverages in relation to their preparation method. We prepared instant coffee and brewed coffee beverages using drip, espresso, and boiling techniques. Coffee extracts were assayed for their CF and CGA contents using HPLC, TPC using colorimetry, platelet aggregation with an aggregometer, and COX activity using ELISA. The findings have shown all coffee extracts, except the decaffeinated types, contained nearly equal amounts of CF, CGA, and TPC. Inhibitory effects of coffee extracts on platelet aggregation differed depending on the activation pathways induced by different agonists. All espresso, drip and boiled coffee extracts caused dose dependent inhibition of platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid (ARA). The most marked inhibition was seen at low doses of collagen or ARA. Espresso and drip extracts inhibited collagen-induced platelet aggregation more than purified caffeine or CGA. Espresso, boiled and drip coffee extracts were also a more potent inhibitors of COX-1 and COX-2 than purified caffeine or CGA. We conclude that inhibition of platelet aggregation and COX-1 and COX-2 may contribute to anti-platelet and anti-inflammatory effects of espresso and drip coffee extracts.


Assuntos
Coffea/química , Café/química , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Ácido Clorogênico/química , Ácido Clorogênico/farmacologia , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Agregação Plaquetária/efeitos dos fármacos
8.
Molecules ; 25(21)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33172028

RESUMO

Saponins comprise a heterogenous group of chemical compounds containing a triterpene or steroid aglycone group and at least one sugar chain. They exist as secondary metabolites, occurring frequently in dicotyledonous plants and lower marine animals. Plant saponin extracts or single saponins have indicated antiplatelet and anticoagulant activity. Venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism, is a multifactorial disease influenced by various patient characteristics such as age, immobility, previous thromboembolism and inherited thrombophilia. This mini-review (1) evaluates the current literature on saponins as modulators of the coagulation system, (2) discusses the impact of chemical structure on the modulation of the coagulation system, which may further provide a basis for drug or supplement design, (3) examines perspectives of their use in the prevention of VTE. It also describes the molecular mechanisms of action of the saponins involved in the prevention of VTE.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Saponinas/farmacologia , Trombose Venosa/prevenção & controle , Animais , Ácido Araquidônico/metabolismo , Coagulação Sanguínea/fisiologia , Humanos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Glicoproteínas da Membrana de Plaquetas/metabolismo , Embolia Pulmonar/prevenção & controle , Saponinas/efeitos adversos , Saponinas/química , Saponinas/uso terapêutico
9.
Molecules ; 25(21)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143291

RESUMO

Inflammation, thrombosis and oxidative stress are rarely studied together when wine's biological activity is concerned; hence the existing literature lacks a holistic point of view in the biological outcome. The scope of the present study is to parallel evaluate the effect of wine extracts on those mechanisms. Ten wine varieties and two different extraction methods were used leading to five extracts for each wine: total lipids (TL) and fractions with different phenolic compound classes (FI, FII, FIII and FIV). Their effect on oxidative stress, platelet aggregation and the secretion of cytokines from mononuclear cells was measured and a biological score was calculated. FII of white wines is the most potent extract and the extracts FIII and TL are following. Specifically, FII had higher anti-oxidant and anti-inflammatory score while all three fractions had a similar anti-platelet score. Furthermore, FII and FIII extracts were the most potent red wine extracts and revealed the highest anti-oxidant and anti-inflammatory scores. White wine FII extracts were more potent than the red wine ones while FI and FIV extracts of red wine were more potent than the white wine ones. In conclusion, the protective effect of a wine is independent of its color but is strongly associated with its microconstituents profile. FII extract revealed the highest biological score and further examination is needed in order to identify the compounds that are responsible for the aforementioned actions.


Assuntos
Anti-Inflamatórios , Antioxidantes , Plaquetas/metabolismo , Frutas/química , Inibidores da Agregação Plaquetária , Agregação Plaquetária/efeitos dos fármacos , Vitis/química , Vinho , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia
10.
Biochem Pharmacol ; 181: 114149, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32663453

RESUMO

Snake venoms consist of a complex mixture of many bioactive molecules. Among them are disintegrins, which are peptides without enzymatic activity, but with high binding affinity for integrins, transmembrane receptors that function to connect cells with components of the extracellular matrix. Integrin-mediated cell attachment is critical for cell migration and dissemination, as well as for signal transduction pathways involved in cell growth. During tumor development, integrins play key roles by supporting cancer cell proliferation, angiogenesis, and metastasis. The recognition that snake venom disintegrins can block integrin functions has spawned a number of studies to explore their cancer therapeutic potential. While dozens of different disintegrins have been isolated, none of them as yet has undergone clinical evaluation in cancer patients. Among the best-characterized and preclinically most advanced disintegrins is vicrostatin (VCN), a recombinant disintegrin that was rationally designed by fusing 62 N-terminal amino acids derived from the disintegrin contortrostatin with 6 C-terminal amino acids from echistatin, the disintegrins from another snake species. Bacterially produced VCN was shown to target multiple tumor-associated integrins, achieving potent anti-tumor and anti-angiogenic effects in in vitro and in vivo models in the absence of noticeable toxicity. This review will introduce the field of snake venom disintegrins as potential anticancer agents and illustrate the translational development and cancer-therapeutic potential of VCN as an example.


Assuntos
Antineoplásicos/farmacologia , Desintegrinas/farmacologia , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Desintegrinas/química , Desintegrinas/uso terapêutico , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Venenos de Serpentes/química , Venenos de Serpentes/metabolismo
11.
Int J Biol Macromol ; 163: 317-326, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32629053

RESUMO

The current study deals with the purification and characterization of non-enzymatic glycoprotein (NEGp) from flax seed buffer extract. Sephadex G-100 and DEAE-A25 column chromatography techniques were employed to isolate NEGp. NEGp showed single sharp band at 29 kDa region on 10% SDS-PAGE, and under reduced and non-reduced conditions revealed its monomeric nature. Besides, NEGp taken up the PAS stain at 29 kDa region reveals the presence of carbohydrate moiety. Purity of NEGp was adjudged by RP-HPLC, as it revealed a single sharp peak at the retention time of 3.4 min. The exact molecular mass of NEGp was found to be 26 kDa which was confirmed by MALDI-TOF. Circular di-chromism spectra of NEGp showed 12.0% α-helix, 24.3% α-helix turn and 63.7% random coils without beta pleated sheets. NEGp was found to exhibit anticoagulant activity by extending clotting time of both platelet rich plasma and platelet poor plasma from control 240 s to 1800 s and 280 s to 2100 s respectively at the concentration of 8 µg. NEGp inhibited the agonists such as ADP, epinephrine and arachidonic acid induced platelet aggregation in washed platelets. The percentage of inhibition was found to be 70%, 80% and 60% respectively. While, it did not interfere in thrombin, PAF and collagen induced platelet aggregation. NEGp did not hydrolyse RBC membrane, devoid of haemorrhagic and edema inducing properties in experimental mice.


Assuntos
Anticoagulantes/isolamento & purificação , Anticoagulantes/farmacologia , Linho/química , Glicoproteínas/isolamento & purificação , Glicoproteínas/farmacologia , Inibidores da Agregação Plaquetária/isolamento & purificação , Inibidores da Agregação Plaquetária/farmacologia , Sementes/química , Anticoagulantes/química , Coagulação Sanguínea/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Glicoproteínas/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Inibidores da Agregação Plaquetária/química , Proteólise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
12.
Nutrients ; 12(6)2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32545505

RESUMO

Platelet hyper-activation and platelet microparticles (PMPs) play a key role in the pathogenesis of cardiovascular diseases. Dietary polyphenols are believed to mimic antiplatelet agents by blunting platelet activation receptors via its antioxidant phenomenon. However, there is limited information on the anti-platelet activity of grain-derived polyphenols. The aim of the study is to evaluate the effects of sorghum extract (Shawaya short black 1 variety), an extract previously characterised for its high antioxidant activity and reduction of oxidative stress-related endothelial dysfunction, on platelet aggregation, platelet activation and PMP release. Whole blood samples collected from 18 healthy volunteers were treated with varying non-cytotoxic concentrations of polyphenol-rich black sorghum extract (BSE). Platelet aggregation study utilised 5 µg/mL collagen to target the GPVI pathway of thrombus formation whereas adenine phosphate (ADP) was used to stimulate the P2Y1/P2Y12 pathway of platelet activation assessed by flow cytometry. Procaspase-activating compound 1 (PAC-1) and P-selectin/CD62P were used to evaluate platelet activation- related conformational changes and degranulation respectively. PMPs were isolated from unstimulated platelets and quantified by size distribution and binding to CD42b. BSE treatment significantly reduced both collagen-induced platelet aggregation and circulatory PMP release at 40 µg/mL (p < 0.001) when compared to control. However, there was no significant impact of BSE on ADP-induced activation-dependent conformational change and degranulation of platelets. Results of this study suggest that phenolic rich BSE may confer cardio-protection by modulating specific signalling pathways involved in platelet activation and PMP release.


Assuntos
Micropartículas Derivadas de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Polifenóis/farmacologia , Sorghum/química , Antioxidantes/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Citometria de Fluxo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Testes de Função Plaquetária
13.
Blood Coagul Fibrinolysis ; 31(5): 293-302, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32332278

RESUMO

: To understand the RBC protecting efficiency and antiplatelet activity of methanolic extract of Caesalpinia crista coat (MECCC). RBC-protecting activity of MECCC was evaluated using assays, such as DPPH, level of lipid peroxidation, protein carbonyl content, superoxide dismutase and catalase as a marker of oxidative stress whereas, platelet aggregation inhibition was performed using human platelet-rich plasma (PRP). MECCC showed about 76% of DPPH-scavenging activity, with an IC50 value of 71.89 µg/ml. The MECCC reduced the level of lipid peroxidation and protein carboxylation in RBC caused by NaNO2 in a dose-dependent manner. In addition, MECCC normalized the levels of superoxide dismutase (SOD) and catalase (CAT) in oxidative stress-induced RBC in a dose-dependent manner. This suggested the protective effect of MECCC on RBC against oxidative stress. Furthermore, MECCC also exhibited mild antiplatelet activity by inhibiting both ADP and epinephrine agonists that induced platelet aggregation. The noticed inhibition percentage was found to be 28 and 23%, respectively at the concentration of 150 µg. Interestingly, MECCC did not hydrolyse the RBC suggesting its nontoxic properties. MECCC possesses protective effect of RBC against NaNO2 (10 mmol/l) induce oxidative stress and inhibits platelet aggregation.


Assuntos
Antioxidantes/farmacologia , Caesalpinia/química , Eritrócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Antioxidantes/química , Eritrócitos/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Extratos Vegetais/química , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Nitrito de Sódio/efeitos adversos
14.
Cardiovasc Hematol Agents Med Chem ; 17(2): 115-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622211

RESUMO

AIM: This study aims to find out the components responsible for the antithrombotic activity of Nelumbo nucifera. MATERIAL AND METHODS: Petroleum ether, chloroform and hydroalcoholic extracts of whole plant of Nelumbo nucifera (Lotus) were prepared and assessed for its thrombolytic, anti-platelet aggregation activity and bleeding time. The extracts were further analyzed through HPTLC and GC-MS. Statistical analysis was conducted through ANOVA trailed by Tukey's multiple comparison test test. RESULTS: Hydroalcoholic extract showed the highest activity at the concentration of 400µg/ml in thrombolytic assay (42.03 ± 5.76), anti-platelet aggregation assay (57.93 ± 1.68) and bleeding time (70.17 ± 2.16) in comparison to clopodigrel (33.76 ± 3.43), aspirin (66.55 ± 1.86) and aspirin (93.85 ± 2.75) at the concentration of 100 µg/ml respectively. 25 peaks were identified through GC-MS, out of which, ferulic acid (14.2µ/g) and quercetin (5.4 µ/g) are active chemical compounds. HPTLC showed different chromatograms in hydroalcoholic extracts like (1) chlorogenic, (2) quercetin, (3) benzoic acid, (4) caffeic acid, (5) ferulic acid, (6) kaempferol, and (7) gallic acid. CONCLUSION: Based on these findings, flavonoids present in hydroalcoholic extract may be developed into a drug for clinical application for the treatment of thrombosis in patients.


Assuntos
Fibrinolíticos/uso terapêutico , Flavonoides/uso terapêutico , Nelumbo/química , Extratos Vegetais/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Trombose/tratamento farmacológico , Animais , Tempo de Lise do Coágulo de Fibrina , Fibrinolíticos/química , Flavonoides/química , Masculino , Extratos Vegetais/química , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Ratos Wistar , Terapia Trombolítica
15.
Molecules ; 24(19)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597284

RESUMO

Sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson) is a small tree or bush. It belongs to the Elaeagnaceae family, and has been used for many years in traditional medicine in both Europe and Asia. However, there is no data on the effect of sea buckthorn leaves and twigs on the properties of blood platelets. The aim of the study was to analyze the biological activity of phenolic extracts from leaves and twigs of sea buckthorn in blood platelets in vitro. Two sets of extracts were used: (1) phenolic compounds from twigs and (2) phenolic compounds from leaves. Their biological effects on human blood platelets were studied by blood platelet adhesion, platelet aggregation, arachidonic acid metabolism and the generation of superoxide anion. Cytotoxicity was also evaluated against platelets. The action of extracts from sea buckthorn twigs and leaves was compared to activities of the phenolic extract (a commercial product from the berries of Aronia melanocarpa (Aronox®) with antioxidative and antiplatelet properties. This study is the first to demonstrate that extracts from sea buckthorn leaves and twigs are a source of bioactive compounds which may be used for the prophylaxis and treatment of cardiovascular pathologies associated with blood platelet hyperactivity. Both leaf and twig extracts were found to display anti-platelet activity in vitro. Moreover, the twig extract (rich in proanthocyanidins) displayed better anti-platelet potential than the leaf extract or aronia extract.


Assuntos
Elaeagnaceae/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Inibidores da Agregação Plaquetária/farmacologia , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/isolamento & purificação
16.
BMC Complement Altern Med ; 19(1): 236, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481052

RESUMO

BACKGROUND: Syzygium cumini (L.) Skeels. is one of the very popular traditionally used medicinal plants with numerous pharmacological activities including antioxidant, hypoglycemic and anti-inflammatory. However, actions of S. cumini on blood coagulation and other parameters of blood were poorly pharmacologically studied. Therefore, aim of this present investigation is to examine the effects of methanolic extract of S. cumini on blood coagulation and anticoagulation factors in healthy white albino rabbits at different doses. METHODS: Blood samples were drawn twice during this study and biochemical assays were performed to determine the effect on different parameters such as coagulation, anticoagulation, hematological, Protein C (PC) and thrombin antithrombin (TAT) complex and platelet aggregation. RESULTS: The results showed significant increase in RBCs, hemoglobin, hematocrit and platelets counts up to 1.4 × 103/cm, 2.2 g/dl, 6%, 248.2 × 103/cm respectively. While, thrombin and bleeding time were also prolonged in dose dependent manner which is highly significant (p ≤ 0.005) as compared to control. Similarly, highly significantly increased (p ≤ 0.005) in levels of protein C, thrombin antithrombin complex at dose of 500 mg/kg were observed. Whereas, levels of platelets aggregation and fibrinogen were decreased at high doses. CONCLUSION: The obtained findings of hematological and coagulation tests concludes possibly S. cumini possess anticoagulant and antiplatelet effects.


Assuntos
Anticoagulantes/farmacologia , Extratos Vegetais/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Syzygium/química , Animais , Anticoagulantes/química , Coagulação Sanguínea/efeitos dos fármacos , Masculino , Extratos Vegetais/química , Folhas de Planta/química , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Coelhos
17.
Chin J Nat Med ; 17(8): 591-599, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472896

RESUMO

Whitmania pigra has been used as a traditional Chinese medicine (TCM) for promoting blood circulation, alleviating blood coagulation, activating meridians and relieving stasis for several hundred years. However, the therapeutic components of this species, especially proteins and peptides were poorly exploited. Until now only a few of them were obtained by using chromatographic isolation and purification. In recent decade, transcriptome techniques were rapidly developed, and have been used to fully reveal the functional components of many animal venoms. In the present study, the cDNA of the salivary gland of Whitmania pigra was sequenced by illumina and the transcriptome was assembled by using Trinity. The proteome were analysed by LC-MS/MS. Based on the data of the transcriptome and the proteome, a potential antiplatelet protein named pigrin was found. Pigrin was cloned and expressed using P. pastoris GS115. The antiplatelet andantithrombotic bioactivities of pigrin were tested by using aggregometer and the rat arterio-venous shunt thrombosis model, respectively. Thebleeding time of pigrin was measured by a mice tail cutting method. The docking of pigrin and protease-activated receptor 1 (PAR1) or collagen were conducted using the ZDOCK Server. Pigrin was able to selectively inhibit platelet aggregation stimulated by PAR1 agonist and collagen. Pigrin attenuated thrombotic formation in vivo in rat, while did not prolong bleeding time at its effective dosage. There are significant differences in the key residues participating in binding of Pigrin-Collagen complex from Pigrin-PAR1 complex. In conclusion,a novel PAR1 inhibitor pigrin was found from the leech Whitmania pigra. This study helped to elucidate the mechanism of the leech for the treatment of cardiovascular disorder.


Assuntos
Sanguessugas/química , Receptor PAR-1/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Modelos Animais de Doenças , Fibrinolíticos/química , Fibrinolíticos/isolamento & purificação , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Perfilação da Expressão Gênica , Sanguessugas/genética , Sanguessugas/metabolismo , Camundongos Endogâmicos ICR , Modelos Moleculares , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/isolamento & purificação , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Proteômica , Ratos Sprague-Dawley , Glândulas Salivares/química , Glândulas Salivares/metabolismo , Trombose/prevenção & controle
18.
Arch Pharm Res ; 42(10): 862-878, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493264

RESUMO

Ginseng is the most frequently used herbal medicine for immune system stimulation and as an adjuvant with prescribed drugs owing to its numerous pharmacologic activities. It is important to investigate the beneficial effects and interaction of ginseng with therapeutic drugs. This review comprehensively discusses drug metabolizing enzyme- and transporter-mediated ginseng-drug interaction by analyzing in vitro and clinical results with a focus on ginsenoside, a pharmacologically active marker of ginseng. Impact of ginseng therapy or ginseng combination therapy on diabetic patients and of ginseng interaction with antiplatelets and anticoagulants were evaluated based on ginseng origin and ginsenoside content. Daily administration of Korean red ginseng (0.5-3 g extract; dried ginseng > 60%) did not cause significant herb-drug interaction with drug metabolizing enzymes and transporters. Among various therapeutic drugs administered in combination with ginseng, adjuvant chemotherapy, comprising ginseng (1-3 g extract) and anticancer drugs, was effective for reducing cancer-related fatigue and improving the quality of life and emotional scores. Limited information regarding ginsenoside content in each ginseng product and plasma ginsenoside concentration among patients necessitates standardization of ginseng product and establishment of pharmacokinetic-pharmacodynamic correlation to further understand beneficial effects of ginseng-therapeutic drug interactions in future clinical studies.


Assuntos
Anticoagulantes/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Ginsenosídeos/farmacologia , Hipoglicemiantes/farmacologia , Neoplasias/tratamento farmacológico , Panax/química , Inibidores da Agregação Plaquetária/farmacologia , Anticoagulantes/química , Antineoplásicos Fitogênicos/química , Diabetes Mellitus/tratamento farmacológico , Ginsenosídeos/química , Interações Ervas-Drogas , Humanos , Hipoglicemiantes/química , Inibidores da Agregação Plaquetária/química
19.
Molecules ; 24(8)2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-31013947

RESUMO

Many Premna species have been used in traditional medicine to treat hypertension and cardiac insufficiency, and as a tonic for cardiac-related problems. Some have been reported to possess cardiovascular protective activity through several possible mechanisms, but not Premna foetida. In the present study, the methanol extract of P. foetida leaves (PFM) and its isolated compounds were evaluated for their ability to inhibit copper-mediated human low-density lipoprotein (LDL) oxidation and arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation. Six flavonoids, three triterpenoids, vanillic acid and stigmasterol were successfully isolated from PFM. Of the isolated compounds, quercetin was the most active against LDL oxidation (IC50 4.25 µM). The flavonols were more active than the flavones against LDL oxidation, suggesting that hydroxyl group at C-3 and the catechol moiety at B-ring may play important roles in protecting LDL from oxidation. Most tested flavonoids showed stronger inhibition towards AA-induced than the ADP-induced platelet aggregation with apigenin exhibiting the strongest effect (IC50 52.3 and 127.4 µM, respectively) while quercetin and kaempferol showed moderate activity. The results suggested that flavonoids, especially quercetin, apigenin and kaempferol were among the major constituents of P. foetida responsible for anti-LDL oxidation and anti-platelet aggregation.


Assuntos
Plaquetas/metabolismo , Flavonoides , Lamiaceae/química , Lipoproteínas LDL/metabolismo , Extratos Vegetais , Folhas de Planta/química , Inibidores da Agregação Plaquetária , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/farmacologia , Ácido Araquidônico/farmacologia , Plaquetas/citologia , Flavonoides/química , Flavonoides/farmacologia , Humanos , Lipoproteínas LDL/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia
20.
Int J Biol Macromol ; 131: 787-797, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30876901

RESUMO

The recent study deals with the synthesis and characterization of silver nanoparticles bounded to Selaginella bryopteris (Sanjeevini) Plant extract (SPE) as reducing and capping agents. Selaginella bryopteris plant extract silver nanoparticles (SPE@Ag-NPs) was characterized by PXRD, UV-Vis., FESEM, TEM and EDX. The highly stable SPE@Ag-NPs was found promising as antibacterial and antifungal agents when tested against human pathogens S. aureus, E. coli, and A. niger respectively. Furthermore, SPE@Ag-NPs found to show anticoagulant property by enhancing the clotting time of citrated human PRP as well as PPP from the control 160 s to 220 s and 160 s to 284 s respectively. However, SPE@Ag-NPs exhibited mild antiplatelet activity by inhibiting specifically agonist ADP induced platelet aggregation of about 23% at the concentration of 30 µg. Fascinating, SPE@Ag-NPs did not alter the agonist epinephrine-induced platelet function even at the increased dose. Interestingly, SPE@Ag-NPs did not induce edema and hemorrhage in the experimental mice and also did not hydrolyze RBC cells suggesting its nontoxic property. In conclusion, SPE@Ag-NPs was non-toxic and found to exhibit antibacterial, antifungal, anticoagulant and antiplatelet properties. Thus, SPE@Ag-NPs would be a better candidate in the biomedical field especially to treat thrombotic disorders.


Assuntos
Anti-Infecciosos/farmacologia , Anticoagulantes/farmacologia , Nanopartículas Metálicas/química , Extratos Vegetais/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Selaginellaceae/química , Prata/química , Anti-Infecciosos/química , Anticoagulantes/química , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Fenômenos Químicos , Técnicas de Química Sintética , Química Verde , Humanos , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Inibidores da Agregação Plaquetária/química , Prata/farmacologia , Análise Espectral
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