Simultaneous effect of ursolic acid and oleanolic acid on epidermal permeability barrier function and epidermal keratinocyte differentiation via peroxisome proliferator-activated receptor-alpha.
Ursolic acid (UA) and oleanolic acid (ONA) are pentacyclic triterpenoids, which naturally occur in many medicinal herbs and plants. Recent research revealed that several pharmacological effects could be attributed to UA and ONA, such as anti-tumor, anti-inflammatory and anti-microbial activities. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery and normal skin, both flanks of hairless mice were topically treated with either 0.01-0.1 mg/mL UA or 0.1-1.0 mg/mL ONA after tape stripping and transepidermal water loss (TEWL) were assessed, and then hydration and TEWL were measured for 3 weeks with application of UA and ONA (2 mg/mL). We also investigated the morphological changes using light (LM) and electron microscopic (EM) examination. Finally, we observed that UA and ONA stimulated epidermal keratinocyte differentiation via peroxisome proliferator-activated receptor (PPAR)-alpha using Western immunoblotting. The recovery rate of epidermal permeability barrier after tape stripping increased in the UA- and ONA-treated groups (0.1 mg/mL UA and 0.5 mg/mL ONA) at 6 h to more than 20% when compared to the vehicle-treated group (P < 0.05). In both groups, hydration was increased compared to the vehicle group from 1 week without TEWL alteration (P < 0.05). An LM finding showed that epidermal thickening was frequently observed (UA > ONA > vehicle). EM examination revealed an increase in secretion and in the number of lamellar bodies in treated groups and that complete formation of lipid bilayers was also prominent (ONA > UA > vehicle). Protein expression of PPAR-alpha, involucrin, loricrin and filaggrin increased twofold and threefold in HaCaT cells treated for 24 h with either ONA (10 micromol/L) or UA (10 micromol/L), respectively, reflecting that the UA and ONA can improve the recovery of skin barrier function and induce epidermal keratinocyte differentiation via PPAR-alpha. Taken together, these results suggest that UA and ONA will be pertinent candidates for the improvement of epidermal permeability barrier function.
Lim
Suk Won
SW
R&D Center for Skin Science and Cosmetics, ENPRANI, Inchon, Korea.
Hong
Seung Phil
SP
Jeong
Sung Won
SW
Kim
Bora
B
Bak
Hana
H
Ryoo
Hee Chang
HC
Lee
Seung Hun
SH
Ahn
Sung Ku
SK
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects*; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D008854:Microscopy, Electron; D009828:Oleanolic Acid / Q000494:pharmacology*; D047493:PPAR alpha / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011498:Protein Precursors / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000473:pathology; D014315:Triterpenes / Q000494:pharmacology*; D014870:Water Loss, Insensible / Q000187:drug effects; D000097245:Ursolic Acid
D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D009828:Oleanolic Acid; D047493:PPAR alpha; D011498:Protein Precursors; D014315:Triterpenes; D000097245:Ursolic Acid; C064554:loricrin; C032253:involucrin