Neuroprotective Effect of a poly-phytocompound formula against β-Amyloid Induced Neurotoxicity in Rat Hippocampus: Involvement of PLC and MEK/ERK Signaling Pathways

F Marotta1, A Polimeni1, Y Naito2, V Soresi4, H Yang3, P Signorelli1, K Zhong3, DH Chui3
1ReGenera. Research Group for Aging-Intervention, Milano, Italy; 2Seyukai Medical Institute & Clinic, Nagoya, Japan; 3Neuroscience Research Institute, Peking University, Beijing, China;. 4Octopus Scientific Association of Bio-Prevention, Milano, Italy.

A number of natural compounds such as anthocyanins, phosphatidylserine, polyphenols, L-alpha glycerylphosphorylcholine and others have shown on experimental basis exert neuroprotective effects. This study examined whether a poly-phytocompound formula (PPF) containing most of them (alpha-glyceryl phosphoryl choline, conjugated phosphatidylserine-DHA, vinpocetine, Leucoselect, Phytosome, containing 50 mg vitis vinifera procyanidin extract complexed with soy phospholipids, vaccinium angustifolium extract standardized to 4.9% total anthocyanins, Withania somnifera extract standardized to 8% withanolide glycoside conjugates, uridine-5′-monophosphate, humulus lupulus, zingiber officinale, rosmarinus officinalis, LEF, Ft Lauderdale, USA) could antagonize the neurotoxicity induced by amyloid P-peptide (A(3) in rat hippocampal organotypic slice cultures, and the possible mechanism was also explored. Treatment with PPF (concentration ranges from 1.7 mM to 10 mM) significantly decreased the cell death in hippocampal slices in the presence of A(3 at 24h, 48h and 72h, and this neuroprotective effect of PPF against AP was not in a dose-dependent manner, FBP 3.5 mM has better neuroprotective effect than that of other PPF concentration groups. Treatment with PPF slightly but significantly increases the ATP levels in hippocampal slices in the presence of A(3. However, the increment of ATP levels was similar among various PPF concentration groups.

Neuroprotective effect of PPF 3.5 mM against A(3 induced neurotoxicity in hippocampal slices was attenuated by addition of phospholipase C (PLC) inhibitor, U73122, mitogen activated extracellular signal protein kinase (MEK) inhibitor, U0126, or extracellular signal activated protein kinase (ERK) inhibitor, PD98059 at 24h, 48h and 72h. However, co-treatment with these three kinds of inhibitors did not change the PPF’s effect on ATP levels. Our results suggested PPF has significant neuroprotective effect against A(3 induced neurotoxicity in hippocampal slice cultures and PPF plays role not only as an alternative energy source, but also a modulator of PLC and MEK/ERK pathways to regulate the cellular response and survival.

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