A neuroprotective herbal mixture inhibits caspase-3-independent apoptosis in retinal ganglion cells.
It was previously demonstrated that Menta-FX, a mixture of Panax quinquefolius L. (PQE), Ginkgo biloba (GBE), and Hypericum perforatum extracts (HPE), enhances retinal ganglion cell survival after axotomy. However, the mechanisms of neuroprotection remain unknown. The aim of this study is to elucidate the neuroprotective mechanisms of Menta-FX. Since PQE, GBE and HPE have all been observed to display anti-oxidative property, the involvement of anti-oxidation in Menta-FX's neuroprotective effect was investigated. Menta-FX lowered nitric oxide (NO) content in axotomized retinas without affecting nitric oxide synthase activity, suggesting that Menta-FX possibly exhibited a NO scavenging property. In addition, the effect of Menta-FX on the frequency of axotomy-induced nuclear fragmentation and caspase-3 activation was investigated. Menta-FX treatment significantly reduced nuclear fragmentation in axotomized retinas. Surprisingly, Menta-FX had no effect on caspase-3 activation, but selectively lowered caspase-3-independent nuclear fragmentation in axotomized retinal ganglion cells. In addition, inhibition of PI3K activity by intravitreal injection of wortmannin, a phosphoinositide-3 kinase (PI3K) inhibitor, completely abolished the neuroprotective effect of Menta-FX, indicating that Menta-FX's neuroprotective effect was PI3K-dependent. Data here suggest that Menta-FX displayed a PI3K-dependent, selective inhibition on a caspase-3-independent apoptotic pathway in axotomized RGCs, thus, highlighting the potential use of herbal remedies as neuroprotective agents for other neurodegenerative diseases.
Cheung
Zelda H
ZH
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 1/F, Laboratory block, 21 Sassoon Road, Pokfulam, Hong Kong, China.
Leung
Mason C P
MC
Yip
Henry K
HK
Wu
Wutian
W
Siu
Flora K W
FK
So
Kwok-Fai
KF
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019771:Axotomy; D053148:Caspase 3 / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D013482:Superoxide Dismutase / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D018696:Neuroprotective Agents; D010936:Plant Extracts; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D000077191:Wortmannin
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