New polysaccharide from Nerium indicum protects neurons via stress kinase signaling pathway.
Most of the polysaccharides purified from Chinese medicinal herbs showed anti-tumor and immune-stimulating effects. However, little is known about their effects on neuroprotection. Our previous study has demonstrated that polysaccharides (J2, J3 and J4) isolated from the flowers of Nerium indicum (Oleander) exert partial protection in cortical neurons stressed by beta-amyloid (Abeta) peptides or deprivation of nutrition from serum. In this study, we have isolated and characterized a new polysaccharide from the flowers of N. indicum (named as J6) and aimed to investigate its neuroprotective effects against Abeta-induced apoptosis. Pretreatment of the polysaccharide J6 significantly decreased the activity of caspase-3 as well as the cytotoxicity triggered by Abeta peptides in a dose-dependent manner. In contrast to the activation of survival signaling such as Akt found in J2, J3 and J4 fractions, neuroprotective effects of J6 markedly inhibited Abeta peptide-stimulated phosphorylation of c-Jun N-terminal kinase (JNK-1) as determined by Western blot analysis. Taken together, the polysaccharide J6 isolated from the flowers of N. indicum can serve as potential neuroprotective agent against neuronal death in Alzheimer's disease and the neuroprotective mechanism may primarily rely on inactivation of JNK signaling pathway.
Yu
Man-Shan
MS
Laboratory of Neurodegenerative Diseases, Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong.
Wong
Anita Yuk-Yee
AY
So
Kwok-Fai
KF
Fang
Ji-Nian
JN
Yuen
Wai-Hung
WH
Chang
Raymond Chuen-Chung
RC
D016229:Amyloid beta-Peptides / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D007211:Indoles; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D030007:Nerium / Q000737:chemistry*; D009474:Neurons / Q000187:drug effects*; D018514:Plant Structures / Q000737:chemistry*; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D007211:Indoles; C524559:J6 polysaccharide; D011134:Polysaccharides; C439320:amyloid beta-protein (25-36); C007293:DAPI; D007770:L-Lactate Dehydrogenase; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3