Neuroprotective effects of Brazilian green propolis and its main constituents against oxygen-glucose deprivation stress, with a gene-expression analysis.
Our purpose was to investigate the neuroprotective effects (and the underlying mechanism) exerted by water extract of Brazilian green propolis (WEP) and its main constituents against the neuronal damage induced by oxygen-glucose deprivation (OGD)/reoxygenation in retinal ganglion cells (RGC-5, a rat ganglion cell-line transformed using E1A virus). Cell damage was induced by OGD 4 h plus reoxygenation 18 h exposure. In RGC-5, and also in PC12 (rat pheochromocytoma, neuronal cells), WEP and some of its main constituents attenuated the cell damage. At the end of the period of OGD/reoxygenation, RNA was extracted and DNA microarray analysis was performed to examine the gene-expression profile in RGC-5. Expression of casein kinase 2 (CK2) was down-regulated and that of Bcl-2-related ovarian killer protein (Bok) was up-regulated following OGD stress, results that were confirmed by quantitative reverse transcriptase-PCR (qRT-PCR). These effects were normalized by WEP. Our findings indicate that WEP has neuroprotective effects against OGD/reoxygenation-induced cell damage and that certain constituents of WEP (caffeoylquinic acid derivatives, artepillin C, and p-coumaric acid) may be partly responsible for its neuroprotective effects. Furthermore, the protective mechanism may involve normalization of the expressions of antioxidant- and apoptosis-related genes (such as CK2 and Bok, respectively).
Nakajima
Yoshimi
Y
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Shimazawa
Masamitsu
M
Mishima
Satoshi
S
Hara
Hideaki
H
D000818:Animals; D056705:Apitherapy; D031175:Baccharis; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D001938:Brazil; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000378:metabolism; D011429:Propolis / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D012165:Retinal Ganglion Cells; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011429:Propolis; D006861:Hydrogen Peroxide; D047390:Casein Kinase II; D005947:Glucose; D010100:Oxygen