Baicalein significantly protects human retinal pigment epithelium cells against H₂O₂-induced oxidative stress by scavenging reactive oxygen species and downregulating the expression of matrix metalloproteinase-9 and vascular endothelial growth factor.
OBJECTIVE
Age-related macular degeneration is a leading cause of blindness in the elderly. At a later stage, neovascular or exudative age-related macular degeneration can lead to severe central vision loss that is related to aging-associated cumulative oxidative stress of the human retinal pigment epithelium (hRPE) cells. Early prevention with antioxidants is mandatory. The aim of this study was to determine whether and how baicalein can act as an antioxidant.


METHODS
The methods used included lactate dehydrogenase, 2′,7′-dichloro-fluorescein diacetate, or enzyme-linked immunosorbent assay to measure cell viability, oxygen free radical levels, or the levels of vascular endothelial growth factor (VEGF)/matrix metalloproteinase-9 (MMP-9), respectively.


RESULTS
H₂O₂ dose-dependently reduced the cell viability of hRPE cells. This negative effect was dose-dependently (with a lower effect at 20µM) and significantly counteracted by pretreatment with baicalein (50µM). Treatment with H₂O₂ significantly stimulated the formation of oxygen free radicals. This increase was dose-dependently and significantly blunted by baicalein. Further, treatment with a sublethal dose of H₂O₂ was associated with an upregulation in the levels of VEGF and MMP-9. The increases in these proteins were also dose-dependently (with a lower effect at 20µM) and significantly (50µM) blunted by pretreatment with baicalein.


CONCLUSIONS
This study supports an antioxidative role for baicalein whereby it protects hRPE cells against H₂O₂-induced oxidative stress by downregulating the levels of VEGF and MMP-9, which are increased by H₂O₂.
Liu
Jorn-Hon
JH
Department of Ophthalmology, Cheng Hsin General Hospital , Taipei, Taiwan, Republic of China.
Wann
Hsiung
H
Chen
Mi-Mi
MM
Pan
Wynn H T
WH
Chen
Yei-Ching
YC
Liu
Chi-Ming
CM
Yeh
Ming-Yang
MY
Tsai
Shen-Kou
SK
Young
Mason Shing
MS
Chuang
Hui-Yen
HY
Chao
Fang-Ping
FP
Chao
Hsiao-Ming
HM
D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D044950:Flavanones / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000008:administration & dosage*; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D055213:Retinal Pigment Epithelium / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology
D000975:Antioxidants; D044950:Flavanones; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C006680:baicalein; D006861:Hydrogen Peroxide; D020780:Matrix Metalloproteinase 9