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Métodos Terapéuticos y Terapias MTCI
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1.
Mar Drugs ; 17(9)2019 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-31540318

RESUMEN

This study investigated the anti-obesity effect of a polysaccharide-rich red algae Gelidium amansii hot-water extract (GHE) in high-fat (HF) diet-induced obese hamsters. GHE contained 68.54% water-soluble indigestible carbohydrate polymers. Hamsters were fed with a HF diet for 5 weeks to induce obesity, and then randomly divided into: HF group, HF with 3% guar gum diet group, HF with 3% GHE diet group, and HF with orlistat (200 mg/kg diet) group for 9 weeks. The increased weights of body, liver, and adipose in the HF group were significantly reversed by GHE supplementation. Lower plasma leptin, tumor necrosis factor-α, and interleukin-6 levels were observed in the GHE+HF group compared to the HF group. GHE also increased the lipolysis rate and decreased the lipoprotein lipase activity in adipose tissues. GHE induced an increase in the phosphorylation of AMP-activated protein kinase (AMPK) and the protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and uncoupling protein (UCP)-2 in the livers. The decreased triglyceride and total cholesterol in the plasma and liver were also observed in obese hamsters fed a diet with GHE. These results suggest that GHE exerts a down-regulation effect on hepatic lipid metabolism through AMPK phosphorylation and up-regulation of PPARα and UCP-2 in HF-induced obese hamsters.


Asunto(s)
Fármacos Antiobesidad/administración & dosificación , Suplementos Dietéticos , Obesidad/dietoterapia , Extractos Vegetales/administración & dosificación , Rhodophyta/química , Adenilato Quinasa/metabolismo , Animales , Fármacos Antiobesidad/química , Fármacos Antiobesidad/aislamiento & purificación , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Mesocricetus , Obesidad/etiología , Orlistat/administración & dosificación , Fosforilación/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Transducción de Señal/efectos de los fármacos , Proteína Desacopladora 2/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Agua/química
2.
Eur J Pharm Sci ; 135: 1-11, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31067495

RESUMEN

Obesity is a rapidly growing epidemic, with over one-third of the global population classified as overweight or obese. Consequently, an urgent need exists to develop innovative approaches and technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions of commercial clay platelets (Veegum® HS and LAPONITE® XLG), were delivered as complimentary, bioactive excipients with the potent lipase inhibitor, orlistat, for the inhibition of fat (lipid) hydrolysis. Simulated intestinal lipolysis studies were performed by observing changes in free fatty acid concentration and revealed that a combinatorial effect existed when NSC particles were co-administered with orlistat, as evidenced by a 1.2- to 1.6-fold greater inhibitory response over 60 min, compared to dosing orlistat alone. Subsequently, it was determined that a multifaceted approach to lipolysis inhibition was presented, whereby NSC particles adsorbed high degrees of lipid (up to 80% of all lipid species present in lipolysis media) and thus physically shielded the lipid-in-water interface from lipase access, while orlistat covalently attached and blocked the lipase enzyme active site. Thus, the ability for NSC particles to enhance the biopharmaceutical performance and potency of orlistat is hypothesised to translate into promising in vivo pharmacodynamics, where this novel approach is predicted to lead to considerably greater weight reductions for obese patients, compared to dosing orlistat alone.


Asunto(s)
Fármacos Antiobesidad/química , Arcilla/química , Lipasa/antagonistas & inhibidores , Lípidos/química , Nanopartículas/química , Obesidad/tratamiento farmacológico , Orlistat/química , Compuestos de Aluminio/química , Fármacos Antiobesidad/administración & dosificación , Suplementos Dietéticos , Digestión , Ácidos Grasos/metabolismo , Humanos , Hidrólisis , Absorción Intestinal , Lipasa/química , Lipólisis , Compuestos de Magnesio/química , Orlistat/administración & dosificación , Tamaño de la Partícula , Silicatos/química , Propiedades de Superficie
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