Exploring compounds to be used as cosmetic agents that activate peroxisome proliferator-activated receptor alpha

Objective: The human epidermis is formed by the proliferation and differentiation of keratinocytes adjacent to the basement membrane. The outermost layer. the stratum corneum, is equipped with a barrier function that prevents water evaporation, and intercellular lipids play an important role in this harrier function. When the barrier is functioning normally, evaporation is prevented; however, when barrier function is impaired, moisture evaporates, resulting in dry and rough skin. Therefore, maintenance of normal barrier function is critical for maintaining normal skin function. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is mainly not only involved in lipid metabolism in the liver but is also expressed in the epidermis and is involved in inducing keratinocyte differentiation, promoting lipid production, maintaining barrier function and suppressing skin inflammation. Hence, compounds that activate PPAR alpha are expected to control skin function. Therefore, we identified PPAR alpha activators from among extracts of natural resources that have been approved for use in humans and analysed the effects of these extracts on skin function. Methods: First, extracts of 474 natural resources were screened using a PPAR alpha activator screening cell line independently constructed in our laboratory. Next, reporter assays were performed using the Ga14-chimera system to evaluate whether these extracts act as ligands for PPAR alpha. We then analysed their effect on primary normal human epidermal keratinocyte cells by using real-time RT-PCR. Finally, we evaluated PPAR alpha activation effect by the combination of these extracts. Results: We identified 36 extracts having the effect of activating PPAR alpha. In particular, #419, a Typha angustifolia spike extract, showed concentration-dependent transcriptional activation through PPAR alpha-LBD and was considered to be likely to contain a compound that is a ligand of PPAR alpha. #419 increased the expression of PPAR alpha target genes and genes related to skin function in primary cultured human epidermal keratinocytes. Finally, the use of #419 in combination with nine extracts increased PPAR activity more than twice as much as #419 alone treatment. Conclusions: These results showed that the reporter cell line could be useful for discovering extracts of natural resources and that the identified Typha angustifoha spike extract could he used in cosmetics that activate PPAR alpha, which expected to improve skin function.