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Métodos Terapéuticos y Terapias MTCI
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1.
Eur J Pharmacol ; 874: 172986, 2020 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-32032601

RESUMEN

Diarrhea is a condition in which the individual has about three or more daily bowel movements, followed by changes in stool consistency. It is currently considered as one of the worst public health problems due to the number of cases and deaths involved and difficulty of treatment. Thus, the use of natural products is an alternative for new treatments. Among these possibilities is Farnesol (C15H26O), a sesquiterpene found in different herbal species that has known biological activities. The objective of this study was to evaluate the antidiarrheal activity of Farnesol (FOH). Initially, FOH activity was evaluated in models of diarrhea and enteropooling induced by castor oil and PGE2. To evaluate motility, the opioid and cholinergic pathways were studied. In addition, the effect of FOH was investigated in the secretion model in intestinal loops treated with cholera toxin. FOH was evaluated for the ability to absorb fluids in intestinal loops and interact with GM1 receptors using the ELISA method and molecular docking. The dose of 50 mg/kg of FOH showed the best results in all antidiarrheal activity tests with castor oil and PGE2, being considered as the standard dose, reducing motility by anticholinergic mechanisms. There was a reduction in fluid secretion when FOH interacted directly with GM1 receptors; cholera toxin and molecular docking showed strong interaction between farnesol and these targets. In view of the results presented, the antidiarrheal activity occurs through anticholinergic, anti-inflammatory and anti-secretory action, making farnesol a potential candidate for the development of a new drug to treat diarrheal diseases.


Asunto(s)
Antidiarreicos/farmacología , Antidiarreicos/uso terapéutico , Diarrea/tratamiento farmacológico , Diarrea/metabolismo , Farnesol/farmacología , Farnesol/uso terapéutico , Animales , Aceite de Ricino , Cloruros/metabolismo , Toxina del Cólera , Diarrea/inducido químicamente , Dinoprostona , Femenino , Motilidad Gastrointestinal/efectos de los fármacos , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Secreciones Intestinales/metabolismo , Masculino , Ratones , Simulación del Acoplamiento Molecular , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Receptores de Superficie Celular/metabolismo
2.
Biomed Pharmacother ; 97: 1147-1154, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29136953

RESUMEN

The water-soluble protein fraction obtained from Plumeria pudica (LPPp) latex has previously been demonstrated to have anti-inflammatory and antinociceptive effects. In the present study, LPPp was tested for activity against diarrhea induced by castor oil, prostaglandin E2 (PGE2) or cholera toxin. Different doses of LPPp (10, 20 or 40mg/kg) significantly inhibited the percentage of diarrheal stools (31.18%, 42.97% and 59.70%, respectively) induced by castor oil. This event was followed by significant reduction of both intestinal fluid accumulation (31.42%; LPPp 40mg/kg) and intestinal transit (68.4%; LPPp 40mg/kg). The pretreatment of animals with LPPp (40mg/kg) prevented glutathione and malondialdehyde alterations induced by castor oil. The effects of LPPp against diarrhea induced by castor oil were lost when the fraction was submitted to protein denaturing treatment with heat. LPPp (40mg/kg) also inhibited the average volume of intestinal fluid induced by PGE2 (inhibition of 46.0%). Furthermore, LPPp (40mg/kg) prevented intestinal fluid secretion accumulation (37.7%) and chloride ion concentration (50.2%) induced by cholera toxin. In parallel, colorimetric assays demonstrated that proteinases, chitinases and proteinase inhibitors were found in LPPp. Our data suggest that the antidiarrheal effect of LPPp is due to its protein content and is probably associated with its anti-inflammatory properties.


Asunto(s)
Antidiarreicos/farmacología , Apocynaceae/química , Diarrea/tratamiento farmacológico , Extractos Vegetales/farmacología , Proteínas de Plantas/farmacología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antidiarreicos/administración & dosificación , Antidiarreicos/aislamiento & purificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratones , Extractos Vegetales/administración & dosificación , Proteínas de Plantas/administración & dosificación , Proteínas de Plantas/aislamiento & purificación , Solubilidad , Agua/química
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