The anti-apoptotic and anti-oxidant effect of eriodictyol on UV-induced apoptosis in keratinocytes.
Recently, considerable scientific and therapeutic interest has focused on the structure and functions of the flavonoids. In a previous study, we suggested that hydroxyl (OH) substitutions on specific carbons in the skeleton of the flavonoids might significantly affect their apoptosis-modulating properties. Here, to investigate the effect of various OH substitutions on their diphenylpropane (C6C3C6) skeleton carbons, we selected 10 different flavonoids and assessed their role on UV-induced apoptosis of human keratinocytes, the principal cell type of epidermis. The results showed that 5,7,3',4'-tetrahydroxylflavanone (eriodictyol) and 3,4'-dihydroxy flavone (3,4'-DHF) had a positive effect on cell proliferation of human HaCaT keratinocytes. Treatment with eriodictyol in particular resulted in significant suppression of cell death induced by ultraviolet (UV) light, a major skin-damaging agent. We found that eriodictyol treatment apparently reduced the percentage of apoptotic cells and the cleavage of poly(ADP-ribose) polymerase, concomitant with the repression of caspase-3 activation and reactive oxygen species (ROS) generation. The anti-apoptotic and anti-oxidant effects of eriodictyol were also confirmed in UV-induced cell death of normal human epidermal keratinocyte (NHEK) cells. Taken together, these findings suggest that eriodictyol can be used to protect keratinocytes from UV-induced damage, implying the presence of a complex structure-activity relationship (SAR) in the differential apoptosis-modulating activities of various flavonoids.
Lee
Eung-Ryoung
ER
Department of Animal Biotechnology and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
Kim
Jung-Hyun
JH
Kang
Yong-Jin
YJ
Cho
Ssang-Goo
SG
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation / Q000187:drug effects; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D015394:Molecular Structure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D013473:Sunscreening Agents / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors; D014466:Ultraviolet Rays
D000975:Antioxidants; D044950:Flavanones; D005419:Flavonoids; D017382:Reactive Oxygen Species; D013473:Sunscreening Agents; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; C028288:3',4'-dihydroxyflavone; C007619:eriodictyol