Neuroprotective effects of anti-aging oriental medicine Lycium barbarum against beta-amyloid peptide neurotoxicity.
As aged population dramatically increases in these decades, efforts should be made on the intervention for curing age-associated neurodegenerative diseases such as Alzheimer's disease (AD). Natural plant extracts of Lycium barbarum are well-known to exhibit anti-aging effects. We therefore hypothesized that they exhibit neuroprotective effects against toxins in aging-related neurodegenerative diseases. In this study, we aimed to investigate whether extracts from L. barbarum have neuroprotective effects against toxicity of fibrillar Abeta(1-42) and Abeta(25-35) fragments. Primary rat cortical neurons exposed to Abeta peptides resulted in apoptosis and necrosis. Pre-treatment with extract isolated from L. barbarum significantly reduced the release of lactate dehydrogenase (LDH). In addition, it attenuated Abeta peptide-activated caspases-3-like activity. The extract elicited a typical dose-dependent neuroprotective effect. Effective dosage of this extract was wider than that of a well-known western neuroprotective medicine lithium chloride (LiCl). We have further examined the underlying mechanisms of the neuroprotective effects. In agreement with other laboratories, Abeta peptides induce a rapid activation of c-Jun N-terminal kinase (JNK) by phosphorylation. Pre-treatment of aqueous extract markedly reduced the phosphorylation of JNK-1 (Thr183/Tyr185) and its substrates c-Jun-I (Ser 73) and c-Jun-II (Ser 63). Taken together, we have proved our hypothesis by showing neuroprotective effects of the extract from L. barbarum. Study on anti-aging herbal medicine like L. barbarum may open a new therapeutic window for the prevention of AD.
Yu
Man-Shan
MS
Laboratory of Neurodegenerative Diseases, Department of Anatomy, The University of Hong Kong, Hong Kong.
Leung
Sarana Ka-Yan
SK
Lai
Sau-Wan
SW
Che
Chi-Ming
CM
Zee
Sze-Yong
SY
So
Kwok-Fai
KF
Yuen
Wai-Hung
WH
Chang
Raymond Chuen-Chung
RC
D000544:Alzheimer Disease / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D018021:Lithium Chloride / Q000494:pharmacology; D032305:Lycium / Q000737:chemistry; D008518:Medicine, East Asian Traditional; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D018692:Antimanic Agents; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D010936:Plant Extracts; C500223:lycium barbarum polysaccharide; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D018021:Lithium Chloride