RESUMO
Astragaloside IV (AS-IV) has been reported to have a prominent antioxidant effect and was proposed as a promising agent for the prevention of neurodegenerative disorders accompanied by cognitive impairment. The present study investigated the ameliorating effect of AS-IV on learning and memory deficits induced by chronic cerebral hypoperfusion in rats. Rats were treated with two doses of AS-IV (10 and 20 mg/kg, i.p.) daily for 28 days starting from the 5th week after permanent bilateral common carotid artery occlusion. AS-IV treatment (at dose of 20 mg/kg) significantly improved the spatial learning and memory deficits assessed using the Morris water maze test in rats with chronic cerebral hypoperfusion. AS-IV significantly attenuated neuronal apoptosis as well as the levels of superoxide dismutase and lipid peroxidation markers, including malondialdehyde and 4-hydroxy-2-nonenal, in the hippocampus. AS-IV also significantly reduced 8-hydroxy-2'-deoxyguanosine expression, a maker of oxidative DNA damage, while significantly inhibited the astrocyte and microglia activation in the hippocampus. The results indicate that AS-IV has therapeutic potential for the prevention of dementia caused by cerebral hypoperfusion and suggest that the ameliorating effect of AS-IV on learning and memory deficits might be the result of suppressing neuronal apoptosis and oxidative damage in the hippocampus.
Assuntos
Antioxidantes/uso terapêutico , Doenças das Artérias Carótidas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Saponinas/uso terapêutico , Triterpenos/uso terapêutico , Animais , Antioxidantes/farmacologia , Apoptose , Proteínas de Ligação ao Cálcio/metabolismo , Doenças das Artérias Carótidas/complicações , Circulação Cerebrovascular , Doença Crônica , Avaliação Pré-Clínica de Medicamentos , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/irrigação sanguínea , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Aprendizagem em Labirinto , Proteínas dos Microfilamentos/metabolismo , Neuroglia/fisiologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Ratos Sprague-Dawley , Saponinas/farmacologia , Triterpenos/farmacologiaRESUMO
It was reported that Dipsaci radix (DR) has a reinforcement effect on the bone-muscle dysfunction in the oriental medical classics and the experimental animal studies. The muscle atrophy was induced by unilateral transection of the sciatic nerve of the rats. Water-extract of DR was used as treatment once a day for 12 days. The muscle weights of the hind limb, atrophic changes, glycogen contents, compositions and cross-section areas of muscle fiber types in soleus and medial gastrocnemius were investigated. Muscle fiber type was classified to type-I and type-II with MHCf immunohistochemistry. Furthermore, Bax and Bcl-2 expressions were observed with immunohistochemiatry. DR treatment significantly increased muscle weights of soleus, medial gastrocnemius, lateral gastrocnemius, and posterior tibialis of the damaged hind limb. DR treatment reduced apoptotic muscle nuclei and hyaline-degenerated muscle fibers in soleus and medial gastrocnemius of the damaged hind limb. DR treatment also significantly increased glycogen contents in medial gastrocnemius of the damaged hind limb. DR treatment significantly attenuated the slow-to-fast shift in soleus of the damaged hind limb but not in medial gastrocnemius. DR treatment significantly increased cross-section areas of type-I and type-II fibers in soleus and medial gastrocnemius of the damaged hind limb. In soleus and medial gastrocnemius, DR treatment significantly reduced Bax positive muscle nuclei in the damaged hind limb. These results suggest that DR treatment has an anti-atrophic effect and an anti-apoptotic effect against myonuclear apoptosis induced by the peripheral nerve damage.