Neuroprotective Effects of Polysaccharides from Wolfberry, the Fruits of Lycium barbarum, Against Homocysteine-induced Toxicity in Rat Cortical Neurons
Affiliations: [a] Laboratory of Neurodegenerative Diseases, Department of Anatomy, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China | [b] Research Centre of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China | [c] State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China | [d] Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
Correspondence:
[*]
Correspondence to: Dr. Raymond C. C. Chang, Department of Anatomy, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China. Tel.: +86 852 2819 9127; Fax: +86 852 2817 0857; E-mail: [email protected].
Abstract: Previous clinical and epidemiological studies have suggested that elevated plasma homocysteine (Hcy) levels increased the risk of Alzheime's disease (AD). Although the underlying mechanisms of its toxicity are elusive, it has been shown that Hcy damages neurons by inducing apoptosis, DNA fragmentation, and tau hyperphosphorylation. Wolfberry (Lycium barbarum) is a fruit that is known for its eye-protective and anti-aging properties in Asian countries. Previous studies from our laboratory have demonstrated that polysaccharides derived from wolfberry (LBA) have the ability to protect neurons from amyloid-β (Aβ) peptide neurotoxicity. We hypothesize that the neuroprotective effects of wolfberry is not limited to Aβ and can also provide protection against other AD risk factors. In this study, we aim to elucidate the neuroprotective effects of wolfberry against Hcy-induced neuronal damage. Our data showed that LBA treatment significantly attenuated Hcy-induced neuronal cell death and apoptosis in primary cortical neurons as demonstrated by LDH and caspase-3 like activity assay. LBA also significantly reduced Hcy-induced tau phosphorylation at tau-1 (Ser198/199/202), pS396 (Ser396), and pS214 (Ser214) epitopes as well as cleavage of tau. At the same time, we also found that the phosphorylation level of p-GSK3β (Ser9/Tyr 216) remained unchanged among different treatment groups at all detected time points. LBA treatment suppressed elevation of both p-ERK and p-JNK. In summary, our data demonstrated that LBA exerted neuroprotective effects on cortical neurons exposed to Hcy. Therefore, LBA has the potential to be a diseasemodifying agent for the prevention of AD.
Keywords: Apoptosis, homocysteine, neuroprotection, tau phosphorylation, Wolfberry
