ABSTRACT
Aß40-induced vascular dysfunction has been implicated in the pathogenesis of Alzheimer׳s disease (AD). In the present study, we investigated the possible protective effects of puerarin against Aß40-induced vascular damage and impairment to angiogenesis in transgenic TG (fli1:EGFP) zebrafish and human endothelial cells. Aß40 peptides at 5µM caused an obvious reduction of vessel branches in the subintestinal vein basket, induced NADPH oxidase-derived reactive oxygen species and impaired vascular endothelial growth factor (VEGF)-dependent angiogenesis. Pretreatment with puerarin attenuated Aß40-induced vessel reduction and impairment to angiogenesis in a dose-dependent manner. In addition, Aß40 decreased VEGF-dependent phosphorylation of Akt and eNOS, whereas puerarin treatment attenuated these detrimental effects. Furthermore, the restoration of Aß40-induced-angiogenesis impairment by puerarin was abolished by either the PI3 kinase inhibitor LY294002 (10µM) or eNOS inhibitor L-NAME. The present study suggests that puerarin exerts its protective action probably through reduction of NADPH oxidase-derived reactive oxygen species overproduction and activation of the PI3K/Akt/eNOS pathways.
Subject(s)
Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/toxicity , Endothelial Cells/drug effects , Isoflavones/pharmacology , Neuroprotective Agents/pharmacology , Vascular Diseases/chemically induced , Vascular Diseases/prevention & control , Animals , Humans , Neovascularization, Physiologic/drug effects , Reactive Oxygen Species/metabolism , Respiratory Burst/drug effects , Vascular Diseases/pathology , ZebrafishABSTRACT
Acupuncture is used as a treatment in stroke patients with aphasia, yet the underlying neural mechanisms are unknown. This study aims to examine the relationship between changes in language function and brain activation using functional magnetic resonance imaging in chronic stroke patients with aphasia who underwent an 8-week acupuncture protocol. Seven chronic stroke patients were identified from a stroke database of a regional acute hospital in Hong Kong between January and July 2007. Patients were treated three times a week over a period of 8 weeks. Four acupoints were stimulated on the weak side of the patient's body. No other rehabilitation was given during the study period. Changes in language function were measured by aphasia quotient (AQ) of Cantonese Aphasia Battery (CAB). Functional magnetic resonance imaging blood oxygen level dependent signals were used to demonstrate the correlation between changes in AQ and brain activation after treatment. The patients were divided into well-recovered and poorly- recovered groups based on their CAB scores at entry. The well-recovered group showed significant improvement in CAB scores after receiving acupuncture treatment. A significant correlation between changes in AQ and blood oxygen level dependent activation in the lesioned Wernicke's speech area was found. These preliminary results suggest that acupuncture may be beneficial to language recovery in chronic stroke patients.
