Diarylheptanoid 7-(3,4 dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene from Curcuma comosa Roxb. protects retinal pigment epithelial cells against oxidative stress-induced cell death.
Chronic exposure to oxidative stress causes damage to retinal pigment epithelial cells which may lead to the development of age-related macular degeneration, the major cause of vision loss in humans. Anti-oxidants provide a natural defense against retinal cell damage. The present study was designed to evaluate the potential anti-oxidant activity and protective effect of two diarylheptanoids isolated from a medicinal herb Curcuma comosa; 7-(3,4 dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound A), and 1,7-diphenyl-4(E),6(E)-heptadien-3-ol (compound B) against oxidative stress (H(2)O(2))-induced human retinal pigment epithelial (APRE-19) cell death. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay indicated that the anti-oxidant activity (IC(50)) of compound A was similar to that of vitamin C. Pre-treatment of ARPE-19 cells with 20 μM compound A for 4h afforded greater protection against the insult from 500 μM H(2)O(2), compared to a similar protection period for compound B. Compound A lowered H(2)O(2)-induced lipid peroxidation, malondialdehyde formation and intracellular reactive oxygen species. Furthermore, compound A ameliorated the H(2)O(2)-induced decrease in anti-oxidant enzyme activities and subsequent apoptotic cell death in ARPE-19 cells in a dose and time-dependent manner. These results suggest that compound A protects ARPE-19 cells against oxidative stress, in part, by enhancing several anti-oxidant defense mechanisms. Therefore, compound A may have therapeutic potential for diseases associated with oxidative stress, particularly degenerative retinal diseases.
Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand.
Thunchnok
T
Jitsanong
Kornnika
K
Khanobdee
Pawinee
P
Piyachaturawat
Kanokpan
K
Wongprasert
D000975:Antioxidants / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D030024:Curcuma / Q000737:chemistry*; D036381:Diarylheptanoids / Q000494:pharmacology* / Q000633:toxicity; D019587:Dietary Supplements; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000633:toxicity; D005979:Glutathione Peroxidase / Q000378:metabolism; D006536:Heptanes / Q000494:pharmacology*; D019850:Heptanol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012162:Retinal Degeneration / Q000517:prevention & control; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
C558048:1,7-diphenyl-4,6-heptadien-3-ol; C558047:7-(3,4 dihydroxyphenyl)-5-hydroxy-1-phenyl-1-heptene; D000975:Antioxidants; D036381:Diarylheptanoids; D016166:Free Radical Scavengers; D006536:Heptanes; D016877:Oxidants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D019850:Heptanol; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase