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1.
Neurochem Res ; 49(12): 3383-3395, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39302597

RESUMEN

Population aging is a global reality driven by increased life expectancy. This demographic phenomenon is intrinsically linked to the epidemic of cognitive disorders such as dementia and Alzheimer's disease, posing challenges for elderly and their families. In this context, the search for new therapeutic strategies to prevent or minimize cognitive impairments becomes urgent, as these deficits are primarily associated with oxidative damage and increased neuroinflammation. Ferulic acid (FA), a natural and potent antioxidant compound, is proposed to be nanoencapsulated to target the central nervous system effectively with lower doses and an extended duration of action. Here, we evaluated the effects of the nanoencapsulated FA on d-galactose (d-Gal)- induced memory impairments. Male Wistar adult rats were treated with ferulic acid-loaded nanocapsules (FA-Nc) or non-encapsulated ferulic acid (D-FA) for 8 weeks concurrently with d-Gal (150 mg/kg s.c.) injection. As expected, our findings showed that d-Gal injection impaired memory processes and increased anxiety behavior, whereas FA-Nc treatment ameliorated these behavioral impairments associated with the aging process induced by d-Gal. At the molecular level, nanoencapsulated ferulic acid (FA-Nc) ameliorated the decrease in ACh and glutamate induced by d-galactose (d-Gal), and also increased GABA levels in the dorsal hippocampus, indicating its therapeutic superiority. Additional studies are needed to elucidate the mechanisms underlying our current promising outcomes. Nanoscience applied to pharmacology can reduce drug dosage, thereby minimizing adverse effects while enhancing therapeutic response, particularly in neurodegenerative diseases associated with aging. Therefore, the strategy of brain-targeted drug delivery through nanoencapsulation can be effective in mitigating aging-related factors that may lead to cognitive deficits.


Asunto(s)
Envejecimiento , Ansiedad , Ácidos Cumáricos , Galactosa , Ácido Glutámico , Trastornos de la Memoria , Ratas Wistar , Ácido gamma-Aminobutírico , Animales , Ácidos Cumáricos/farmacología , Ácidos Cumáricos/uso terapéutico , Masculino , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Ansiedad/tratamiento farmacológico , Ansiedad/metabolismo , Ácido Glutámico/metabolismo , Ratas , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Nanoestructuras , Nanocápsulas
2.
Mini Rev Med Chem ; 21(13): 1625-1637, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33402085

RESUMEN

Bioactive compounds found in food and medicinal plants contribute to maintaining health and treating illnesses. For example, hydroxycinnamic acids, such as ferulic acid, are widely present in nature and have several pharmacological properties, including antioxidant, anti-inflammatory, and beneficial effects in parameters of diabetes and hyperlipidemia. The results of studies in animal models and in vitro experiments of ferulic acid suggest its high therapeutic and preventive potential against several pathological disorders, such as cardiovascular diseases. Therefore, in this review, the bioactivities of ferulic acid on the cardiovascular system are described, including the discussion of the mechanisms of action in the various components of the system. In this review, we discuss the pharmacological properties of this versatile natural product in aspects of cardiovascular health, including cardioprotective and antihypertensive actions, and on the metabolism of lipids, diabetes, and thrombosis.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Ácidos Cumáricos/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/química , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Estrés Oxidativo/efectos de los fármacos , Trombosis/tratamiento farmacológico , Vasodilatación/efectos de los fármacos
3.
Naunyn Schmiedebergs Arch Pharmacol ; 394(1): 49-57, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32780226

RESUMEN

The p-coumaric acid is a phenolic compound present in large quantities in the extract of Baccharis dracunculifolia DC, a Brazilian medicinal plant used to treat gastric ulcer. Given the necessity for finding new chemical components capable of accelerating gastric healing, in this study, the effects of the p-coumaric acid were evaluated in the acetic acid-induced ulcer model in rats, where histological, inflammatory, and oxidative parameters were analyzed. The healing property was also evaluated in the scratch assay on fibroblast cells (L929) and the cytotoxicity of p-coumaric acid was assessed in both L929 and human gastric adenocarcinoma (AGS) cells by MTT assay. The treatment with p-coumaric acid (10 mg/kg, p.o.) for 7 days, twice a day, decreased by 44.6% the acetic acid-induced gastric ulcer compared with the vehicle-treated group. The vehicle control-treated group showed a larger extension of the ulcer base and an extensive damage into the mucosa and submucosa layers, which were mitigated by the treatment with p-coumaric acid. This beneficial effect was also associated with increased levels of mucin and reduced glutathione, decreased amount of lipid hydroperoxides, and increased superoxide dismutase and catalase activities without interfering with the activity of myeloperoxidase in the gastric tissue. The compound promoted the restructuring of the cell monolayer in the scratch test and did not show toxicity in the L929 cell line, while reduced the viability of the AGS, a lineage of human gastric adenocarcinoma. Thus, p-coumaric acid may be considered a natural source for the treatment of gastric ulcers, by reinforcing protective factors of gastric mucosa and by accelerating gastric healing.


Asunto(s)
Antiulcerosos/uso terapéutico , Ácidos Cumáricos/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Ácido Acético , Animales , Antiulcerosos/farmacología , Baccharis/química , Catalasa/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ácidos Cumáricos/aislamiento & purificación , Ácidos Cumáricos/farmacología , Modelos Animales de Enfermedad , Femenino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Glutatión/metabolismo , Humanos , Ratones , Peroxidasa/metabolismo , Fitoterapia , Ratas , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Superóxido Dismutasa/metabolismo
4.
Neurotox Res ; 34(3): 640-648, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29949107

RESUMEN

Molecules exhibiting antioxidant, neuroprotective, and regulatory properties inherent to natural products consumed by humans are gaining attention in biomedical research. Ferulic acid (FA) is a phenolic compound possessing antioxidant and cytoprotective properties. It is found in several vegetables, including sugarcane, where it serves as the main antioxidant component. Here, we compared the antioxidant and cytoprotective effects of FA with those of the total sugarcane aqueous extract (SCAE). Specifically, we assessed biochemical markers of cell dysfunction in rat cortical brain slices and markers of physiological stress in Caenorhabditis elegans upon exposure to toxins evoking different mechanisms of neurotoxicity, including direct oxidative stress and/or excitotoxicity. In rat cortical slices, FA (250 and 500 µM), but not SCAE (~ 270 µM of total polyphenols), prevented the loss of reductive capacity induced by the excitotoxin quinolinic acid (QUIN, 100 µM), the pro-oxidant agent ferrous sulfate (FeSO4, 25 µM), and the dopaminergic pro-oxidant 6-hydroxydopamine (6-OHDA, 100 µM). In wild-type (N2) C. elegans, FA (38 mM) exerted protective effects on decreased survival induced by FeSO4 (15 mM) and 6-OHDA (25 mM), and the motor alterations induced by QUIN (100 mM), FeSO4, and 6-OHDA. In contrast, SCAE (~ 13.5 mM of total polyphenols) evoked protective effects on the decreased survival induced by the three toxic agents, the motor alterations induced by FeSO4, and the reproductive deficit induced by FeSO4. In addition, FA was unable to reverse the decreased survival induced by all these toxins in the skn-1-/- strain (VC1772), which lacks the homolog of mammalian Nrf2, a master antioxidant gene. Altogether, our results suggest that (1) both FA and SCAE afford protection against toxic conditions, (2) not all the effects inherent to SCAE are due to FA, and (3) FA requires the skn-1 pathway to exert its protective effects in C. elegans.


Asunto(s)
Ácidos Cumáricos/uso terapéutico , Síndromes de Neurotoxicidad/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Saccharum/química , Análisis de Varianza , Animales , Animales Modificados Genéticamente , Tasa de Natalidad , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Modelos Animales de Enfermedad , Compuestos Ferrosos/toxicidad , Técnicas In Vitro , Hierro/metabolismo , Locomoción/efectos de los fármacos , Masculino , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/fisiopatología , Oxidopamina/toxicidad , Extractos Vegetales/química , Ácido Quinolínico/toxicidad , Ratas , Ratas Wistar
5.
Chem Biol Interact ; 242: 273-9, 2015 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-26456888

RESUMEN

The objective of this study was to evaluate the potential anticonvulsant effect of isopentyl ferulate, a new ester derived from ferulic acid in mice (Mus musculus) subjected to two models of induced seizures. According to the results obtained, the IF at doses of 25, 50 and 75 mg/kg (i.p.) showed protective effect against induced seizures by pilocarpine (400 mg/kg, i.p.) and pentylenetetrazole (70 mg/kg, i.p.). In the two animal models of seizures, the pretreatment of the IF (25, 50 and 75 mg/kg) with flumazenil blocked the anticonvulsant effect, suggesting that the mechanism of action of this ester derived of ferulic acid may be related to activity in the benzodiazepine-binding site of the GABAA receptor (γ-aminobutyric acid, type A). In addition to the anticonvulsant effect, behavioral changes as neurotoxicity indication were assessed by using the rota rod and open field tests. The results obtained showed that the IF (25, 50 and 75 mg/kg) does not induce significant changes in locomotor activity and motor coordination when compared with the control group, unlike the results presented by diazepam. Thus, these results demonstrate a new pharmacological knowledge of IF with potential application against epileptic seizures. However, further studies are needed to elucidate other neurobiological mechanisms underlying epilepsy.


Asunto(s)
Anticonvulsivantes/farmacología , Conducta Animal/efectos de los fármacos , Ácidos Cumáricos/farmacología , Animales , Anticonvulsivantes/química , Anticonvulsivantes/uso terapéutico , Ácidos Cumáricos/química , Ácidos Cumáricos/uso terapéutico , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Pentilenotetrazol/efectos adversos , Pilocarpina/efectos adversos , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/fisiopatología
6.
J Pharm Pharmacol ; 66(9): 1294-302, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24707860

RESUMEN

OBJECTIVES: Aloysia gratissima aqueous extract (AE) was investigated as a putative protective agent against quinolinic acid (QA)-induced seizures in mice and hippocampal cell damage. Additionally, AE and ferulic acid (FA), the major compound of AE, were tested against neurotoxicity evoked by glutamate or its N-methyl-D-aspartate receptor (NMDAR) agonist, QA on hippocampal slices, in vitro. METHODS: Mice were treated with AE before QA infusion (36.8 nmol/site) and seizures were analysed. Cellular viability and modulation of excitatory amino acid transport were verified in hippocampal slices. In-vitro AE or FA was tested against neurotoxicity induced by glutamate or QA. KEY FINDINGS: AE did not prevent QA-induced seizures; however, it prevented cellular death and disruption of excitatory amino acid transport. In-vitro AE (0.1 or 1.0 mg/ml) or FA (1 or 10 µm), improved cell viability against citotoxicity exerted by glutamate or QA, respectively. Both AE and FA have protective effects depending on activation of the phosphatidylinositol-3 kinase (PI3K) signalling pathway. CONCLUSIONS: AE attenuated QA-induced cell damage possibly involving the glutamate transport modulation through NMDAR interaction. FA shows a similar profile of neuroprotection promoted by AE. Therefore, AE treatment might be a useful strategy in preventing brain damage caused by exacerbation of glutamatergic toxicity in nervous system disorders.


Asunto(s)
Ácido Glutámico/efectos adversos , Hipocampo/efectos de los fármacos , Síndromes de Neurotoxicidad/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Ácido Quinolínico/efectos adversos , Verbenaceae/química , Animales , Transporte Biológico , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ácidos Cumáricos/farmacología , Ácidos Cumáricos/uso terapéutico , Agonistas de Aminoácidos Excitadores/efectos adversos , Aminoácidos Excitadores/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Ratones Endogámicos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Fosfatidilinositol 3-Quinasa/metabolismo , Extractos Vegetales/farmacología , Receptores de N-Metil-D-Aspartato/agonistas , Convulsiones/inducido químicamente , Convulsiones/metabolismo
7.
Molecules ; 18(9): 11526-36, 2013 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-24048285

RESUMEN

BACKGROUND: Regular consumption of fruits and vegetables (e.g., tomatoes) has been shown to be beneficial in terms of reducing the incidence of cardiovascular diseases. The industrial processing of tomatoes into tomato-based products includes several thermal treatments. Very little is known on the effect of tomato industrial processing on antiaggregatory activity and phenolic profile. METHODS: It was assessed the effect of tomato and by-products extracts on platelet aggregation induced by ADP, collagen, TRAP-6 and arachidonic acid. These in vitro antithrombotic properties were further supported in an in vivo model of thrombosis. A set of antiplatelet compounds has been selected for HPLC analysis in the different extracts. RESULTS: Some natural compounds such as chlorogenic, caffeic, ferulic and p-coumaric acids were identified by HPLC in tomatoes and its products may inhibit platelet activation. Red tomatoes, tomato products (sauce, ketchup and juice) and by-products extracts inhibited platelet aggregation induced adenosine 5'-diphosphate, collagen, thrombin receptor activator peptide-6 and arachidonic acid, but to a different extent. Also, pomace extract presents antithrombotic activity. CONCLUSIONS: Processed tomatoes may have a higher content of health-benefiting compounds than fresh ones. Pomace even presents the best antiplatelet activity. Finally, tomato products may be used as a functional ingredient adding antiplatelet activities to processed foods.


Asunto(s)
Frutas/química , Extractos Vegetales/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Solanum lycopersicum/química , Animales , Ácidos Cafeicos/aislamiento & purificación , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/uso terapéutico , Ácido Clorogénico/aislamiento & purificación , Ácido Clorogénico/farmacología , Ácido Clorogénico/uso terapéutico , Ácidos Cumáricos/aislamiento & purificación , Ácidos Cumáricos/farmacología , Ácidos Cumáricos/uso terapéutico , Evaluación Preclínica de Medicamentos , Manipulación de Alimentos , Humanos , Ratones , Ratones Endogámicos C57BL , Fenoles/aislamiento & purificación , Fenoles/farmacología , Fenoles/uso terapéutico , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombosis/tratamiento farmacológico
8.
Rev. chil. cardiol ; 17(2): 92-101, abr.-jun. 1998. tab, graf
Artículo en Español | LILACS | ID: lil-231650

RESUMEN

El tratamiento con prostaciclina en la hipertensión pulmonar primaria (HPP) se ha asociado a una disminución de la mortalidad, resultando en una alternativa terapéutica o como soporte previo al trasplante. Objetivo: determinar predictores clínicos o hemodinámicos de sobrevida en pacientes con HPP tratados con prostaciclina. Métodos: 57 pacientes consecutivos con diagnóstico de HPP evaluados en la Universidad de Alabama, período marzo 92-julio 97. Todos ellos tratados con infusión intravenosa continua de prostaciclína durante 19 meses (2-60), la dosis máxima fue 87 ñ 60 ng/kg/min. Para variables categóricas se utilizó test de Fisher y chi2, t test para variables continuas, y método de regresión logística para análisis multivariado. Se presentan los promedios ñ desviación standard p<0,05 fue considerado significativo. Resultados: edad 39 ñ 15 años, 48 pacientes sexo femenino, 41 pacientes en capacidad funcional IV (72 por ciento). Al final del seguimiento la capacidad funcional mejoró de 3,6 ñ 0, 4 a 3,16 ñ 0,7, p=0,0001, la fracción de eyeccíón ventricular derecha de 29 ñ 14 a 34:ñ 15 por ciento, p=0,0001, la presión sístólica de arteria pulmonar disminuyó de 86 ñ 20 mmHg a 76 ñ 23 mmHg, la resistencia vascular pulmonar de 1038 ñ 581 a 658 ñ 462 dinas/seg/cm-5, p=0,0001 con aumentos del índice cardíaco de 2,17 ñ 0,6 a 3,4 ñ 1,3 It/min/m2, p=0,006. La sobrevida fue de un 53 por ciento (n=30), 5 pacientes tuvieron doble trasplante pulmonar. En el análisis multivariado una capacidad funcional más deteriorada en la evaluación basal fue predictor independiente de mortalidad (OR=60, IC=3-1118), y la mejoría de la capacidad funcional predijo una mayor sobrevida (OR=0,21, IC=0,06-0,8). Estos hallazgos se correlacionaron con disminución de la presión sistólica de arteria pulmonar. Conclusión: nuestros resultados confirman la mejoría funcional y hemodinámica de los pacientes con HPP tratados con prostaciclína, sin embargo la mortalidad continúa siendo elevada. Una mejorcapacidad funcional al inicio de la terapia y una mejoría de ésta fueron asociadas a una mayor sobrevida. Pacientes con síntomas avanzados o refractarios debieran ser evaluados para trasplante


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Epoprostenol/farmacología , Hipertensión Pulmonar/tratamiento farmacológico , Ácidos Cumáricos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Evolución Clínica , Supervivencia sin Enfermedad , Epoprostenol/efectos adversos , Hipertensión Pulmonar/cirugía , Hipertensión Pulmonar/diagnóstico , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Trasplante de Pulmón
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