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1.
Mol Neurobiol ; 56(8): 5671-5688, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30666561

RESUMEN

The roots of Achyranthes bidentata Blume (AB) is commonly used in the treatment of osteoporosis and dementia in traditional Chinese medicine. Pharmacological reports evidenced that AB possessed anti-osteoarthritis effects. However, there is little literature about the anti-dementia activities of AB. The present study was designed to prepare steroid-enriched fraction of AB (ABS) and investigate whether ABS can protect from cognitive dysfunction and neuroinflammation against Aß 1-40-induced Alzheimer's disease (AD) model in rats. ABS only contained 135.11 ± 4.28 mg of ecdysterone per gram. ABS (50 mg/kg) reversed the dysfunction of exploratory activity and memory function on plus-maze and Morris water maze caused by Aß 1-40 in rats. ABS (50 mg/kg) also decreased amyloid deposition, neurofibrillary tangle, neural damage, activated astrocyte, and microglial caused by Aß 1-40. Furthermore, ABS reversed the phenomenon of neural oxidative damage and neuroinflammation, including the higher levels of MDA and cytokines, and the lower activities of antioxidant enzymes and GSH levels caused by Aß 1-40 in rat cortex and hippocampus. Finally, ABS restored the activation of ERK pathway and decreased NF-κB phosphorylation and translocation altered by Aß 1-40. ABS alone (50 mg/kg) promoted cognitive function, activated brain antioxidant defense system, and decreased brain TNF-α levels in sham group. Therefore, ABS has the cognition-promoting and antidementia potential. Steroids especial ecdysterone are major active components of AB. The action mechanism is due to decreasing oxidative stress and neuroinflammation through modulating ERK pathway, NF-κB phosphorylation, and translocation in Aß 1-40-induced AD rat model.


Asunto(s)
Achyranthes/química , Péptidos beta-Amiloides/toxicidad , Encéfalo/patología , Disfunción Cognitiva/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Fragmentos de Péptidos/toxicidad , Esteroides/uso terapéutico , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/patología , Conducta Animal , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/fisiopatología , Citocinas/metabolismo , Ecdisterona/análisis , Glutatión/metabolismo , Hipocampo/enzimología , Inflamación/complicaciones , Inflamación/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/patología , FN-kappa B/metabolismo , Ácido Oleanólico/análisis , Ratas Sprague-Dawley , Triterpenos/análisis , Ácido Ursólico
2.
Nutrients ; 10(10)2018 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-30301204

RESUMEN

The medicinal ferns of Polydiaceae and Davalliaceae species are called "Gusuibu" by Chinese physicians and used as antiaging dietary medicines. Our previous report revealed that Drynaria fortunei (Polydiaceae) protected against 6-hydroxydopamine (6-OHDA)-induced oxidative damage via the PI3K/AKT pathway in B35 neuroblastoma cells. The present study compares the antioxidant phytoconstituent contents and radical scavenging capacities of five Davalliaceae species. The further aim was to clarify the protective mechanism of Davallia mariesii (DM) against 6-OHDA-induced oxidative damage and apoptosis in B35 cells. The results show that Araiostegia perdurans (AP) and DM extracts have better radical scavenging capacities against 1,1-diphenyl-2-picryhydrazyl (DPPH) and reactive oxygen species (ROS) than other Davalliaceae species. However, only DM extract inhibited 6-OHDA autoxidation under cell-free systems and increased cell viability, compared to B35 cells solely exposed to 6-OHDA. DM extract decreased apoptosis and restored mitochondrial expression in 6-OHDA-treated B35 cells. Additional data indicated that DM extract decreased intracellular ROS and nitric oxide levels generated by 6-OHDA exposure. DM extract also restored glutathione (GSH) levels and the activities of glutathione peroxidase and reductase, and then decreased the elevated malondialdehyde (MDA) levels. Finally, DM extract regulated the protein expression of the caspase cascade and PI3K/AKT/GSK-3ß pathways. These results suggest that the protective mechanism of DM extract against 6-OHDA-induced oxidative damage and apoptosis might be related to its radical scavenging capacity, maintaining the mitochondrial function to inhibit the Bcl-2/caspase cascade pathway and activating intracellular antioxidant defenses (GSH recycling, HO-1 and NQO-1) by modulating the activation of the PI3K/AKT/GSK-3ß pathway.


Asunto(s)
Antioxidantes/farmacología , Caspasas/metabolismo , Helechos/química , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Oxidopamina/metabolismo , Extractos Vegetales/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular , Glutatión/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Malondialdehído/metabolismo , Mitocondrias/metabolismo , Neuroblastoma , Enfermedad de Parkinson/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Polypodiaceae , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal
3.
Food Funct ; 5(8): 1956-65, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24971874

RESUMEN

In this study, we demonstrate the antioxidant and protective properties of the aqueous extract of two commercial Polydiaceae plants - Drynaria fortunei (DF) and Pseudodrynaria coronans (PC) against 6-hydroxydopamine (6-OHDA)-induced oxidative damage in B35 neuroblastoma cells. The contents of their phytochemical profiles were determined by spectrophotometric methods and high performance liquid chromatography using a photodiode array detector. DF extract showed better effects than PC extract in scavenging ROS and inhibiting 6-OHDA autoxidation. Following exposure to 6-OHDA, B35 cells showed a marked decrease in cell survival and the activation of intracellular antioxidant enzymes and the PI3K/AKT pathway, and then an increased level of lipid peroxidation. Pretreatment with DF extract blocked these 6-OHDA-induced cellular events. Naringin and epicatechin are major components of DF extract. These results show that DF extract exerts protective effects against 6-OHDA toxicity via radical scavenging activity and an increase in the activation of the PI3K/AKT pathway to elevate the levels of intracellular antioxidant enzymes including HO-1, NQO-1 and glutathione-related enzymes.


Asunto(s)
Estrés Oxidativo/efectos de los fármacos , Oxidopamina/efectos adversos , Extractos Vegetales/farmacología , Polypodiaceae/química , Sustancias Protectoras/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo
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