A neuroprotective herbal mixture inhibits caspase-3-independent apoptosis in retinal ganglion cells

Authors

Zelda H. Cheung, The University of Hong Kong
Mason Chin Pang Leung, The Hong Kong Polytechnic University
Henry K. Yip, The University of Hong Kong
Wutian Wu, The University of Hong Kong
Ka Wai, Flora Siu, Technological and Higher Education Institute of Hong Kong, Vocational Training CouncilFollow
Kwok-Fai So, The University of Hong Kong

Document Type

Journal Article

Publication Date

2008

Keywords

Ganglion cells, Ginkgo biloba, Hypericum perforatum, Optic nerve, Panax quinquefolius L.

DOI

10.1007/s10571-007-9175-8

Abstract

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.

Source Publication

Cellular and Molecular Neurobiology

Volume Number

28

Issue Number

1

ISSN

0272-4340

First Page

137

Last Page

155

Recommended Citation

Cheung, Z.,Leung, M.,Yip, H.,Wu, W.,Siu, K.,& So, K. (2008). A neuroprotective herbal mixture inhibits caspase-3-independent apoptosis in retinal ganglion cells. Cellular and Molecular Neurobiology, 28 (1), 137-155. http://dx.doi.org/10.1007/s10571-007-9175-8