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1.
Fitoterapia ; 175: 105894, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38461867

RESUMO

Thrombosis is currently among the major causes of morbidity and mortality in the World. New prevention and therapy alternatives have been increasingly sought in medicinal plants. In this context, we have been investigating parsley, Petroselinum crispum (Mill.) Nym, an aromatic herb with two leaf varieties. We report here the in vitro, in vivo, and ex vivo anti-hemostatic and antithrombotic activities of a parsley curly-leaf variety. Aqueous extracts of aerial parts (PCC-AP), stems (PCC-S), and leaves (PCC-L) showed significant in vitro antiplatelet activity. PCC-AP extract exhibited the highest activity (IC50 2.92 mg/mL) when using ADP and collagen as agonists. All extracts also presented in vitro anticoagulant activity (APTT and PT) and anti-thrombogenic activity. PCC-S was the most active, with more significant interference in the factors of the intrinsic coagulation pathway. The oral administration of PCC-AP extract in rats caused a greater inhibitory activity in the deep vein thrombi (50%; 65 mg/kg) than in arterial thrombi formation (50%; 200 mg/kg), without cumulative effect after consecutive five-day administration. PCC-AP extract was safe in the induced bleeding time test. Its anti-aggregating profile was similar in ex vivo and in vitro conditions but was more effective in the extrinsic pathway when compared to in vitro results. Apiin and coumaric acid derivatives are the main compounds in PCC-AP according to the HPLC-DAD-ESI-MS/MS profile. We demonstrated for the first time that extracts from different parts of curly parsley have significant antiplatelet, anticoagulant, and antithrombotic activity without inducing hemorrhage, proving its potential as a source of antithrombotic compounds.


Assuntos
Fibrinolíticos , Petroselinum , Extratos Vegetais , Folhas de Planta , Animais , Petroselinum/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Ratos , Masculino , Fibrinolíticos/farmacologia , Fibrinolíticos/isolamento & purificação , Fibrinolíticos/química , Ratos Wistar , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Trombose/tratamento farmacológico , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/isolamento & purificação , Componentes Aéreos da Planta/química , Caules de Planta/química , Hemostáticos/farmacologia , Hemostáticos/isolamento & purificação , Anticoagulantes/farmacologia , Anticoagulantes/isolamento & purificação , Anticoagulantes/química , Plantas Medicinais/química
2.
J Ethnopharmacol ; 260: 112841, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32268203

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cecropia Loefl. species (Urticaceae) are widely spread across the rainforest in tropical and subtropical regions of Central and South America. Inhabitants of different regions of Brazil employ leaves, fruits and sprouts of Cecropia hololeuca Miq. mainly as anti-inflammatory, anti-asthmatic, expectorant, fever suppressant, and against cough. AIM OF THE STUDY: To evaluate the antinociceptive and anti-inflammatory activities of an aqueous leaf extract of C. hololeuca in a murine model of zymosan-induced arthritis (ZIA) and characterize compounds contributing to these effects. MATERIALS AND METHODS: The crude aqueous extract of C. hololeuca (CAE) was obtained by infusion, screened for antinociceptive and anti-inflammatory activities, and fractionated (solvent partition; RP-2 and Sephadex G-25 column chromatography), yielding fractions that were chemically and pharmacologically investigated. TLC, HPLC-DAD, HPLC-DAD-ESI-MS/MS and NMR analyses were peformed. The antinociceptive activity was assessed by means of acetic acid-induced writhing, hot-plate and rota-rod tests. ZIA was used to evaluate the anti-arthritic activity of oral treatment with CAE, butanolic (BF) and aqueous fraction (AF), as well as the fractions obtained from BF (F2, F2-A and F2-B). Rutin, a flavonoid found in C. hololeuca, was also tested. Mechanical hypernociception, joint edema, local neutrophil recruitment and articular TNF-α quantification were performed to measure the severity of arthritis and identify the anti-inflammatory potential of C. hololeuca. RESULTS: CAE (0.03-1 g/kg, p.o.) showed a dose-related inhibitory effect on acetic acid-induced writhing test, but did not change the pain latency in the hotplate test, nor the first fall time on the rota-rod test. In addition, CAE (1 g/kg, p.o.) inhibited by 65% the mechanical hypernociception, 46% the joint edema, 54% the neutrophil recruitment and 53% the articular TNF-α concentration levels in ZIA. BF (0.4 g/kg, p.o.), AF (0.6 g/kg), F2 (0.1 g/kg) and F2-A (0.045 g/kg), but not F2-B (0.055 g/kg), inhibited the mechanical hypernociception, joint edema and neutrophil recruitment in ZIA. Rutin (0.001-0.03 g/kg, p.o.) produced dose-related inhibitory effects in the mechanical hypernociception, joint edema and neutrophil recruitment, and at 0.03 g/kg also inhibited articular TNF-α synthesis after intra-articular zymosan injection. Isoorientin, isovitexin, rutin and isoquercitrin were identified in the most active fraction (F2-A), along with luteolin and apigenin derivatives, tentatively identified as isoorientin-2″-O-glucoside and isovitexin-2″-O-glucoside. CONCLUSION: This study corroborates the popular use by oral route of aqueous preparations of C. hololeuca against joint inflammatory disorders, such as rheumatoid arthritis. Our results demonstrated for the first time that oral administration of rutin shows antinociceptive and anti-inflammatory effects in ZIA, indicating that this flavonoid is one of the immunomodulatory compounds involved in the anti-arthritic activity of C. hololeuca.


Assuntos
Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Artralgia/prevenção & controle , Artrite Experimental/prevenção & controle , Cecropia , Flavonoides/administração & dosagem , Articulações/efeitos dos fármacos , Dor Nociceptiva/prevenção & controle , Extratos Vegetais/administração & dosagem , Rutina/administração & dosagem , Administração Oral , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Artralgia/induzido quimicamente , Artralgia/metabolismo , Artralgia/fisiopatologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Experimental/fisiopatologia , Cecropia/química , Citocinas/metabolismo , Precursores Enzimáticos , Flavonoides/isolamento & purificação , Mediadores da Inflamação/metabolismo , Articulações/metabolismo , Articulações/fisiopatologia , Masculino , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Dor Nociceptiva/induzido quimicamente , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Rutina/isolamento & purificação
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