Honey and Chamomile Activate Keratinocyte Antioxidative Responses via the KEAP1/NRF2 System

Tatsuya Ogawa, 1 Yosuke Ishitsuka, 1 Yoshiyuki Nakamura, 1 Naoko Okiyama, 1 Rei Watanabe, 1, 2 Yasuhiro Fujisawa, 1 Manabu Fujimoto 1, 2 1Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; 2Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Osaka, JapanCorrespondence: Yosuke IshitsukaDepartment of Dermatology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, JapanTel +81-29-853-3128Fax +81-29-853-3217Email yosuke.ishitsuka@md.tsukuba.ac.jpIntroduction: The stratum corneum protects against the entry of pathogens, allergens, and irritants while preventing dehydration. The Kelch-like erythroid cell-derived protein with cap-n-collar homology-associated protein 1 (KEAP1)/NF-E2-related factor 2 (NRF2) system maintains skin barrier homeostasis. Aggregated evidence suggests that NRF2-mediated antioxidative response is hardwired into the stratified squamous epithelia. Honey and chamomile have long been regarded as natural antioxidants. Nonetheless, it is still unclear whether they activate the KEAP1/NRF2 system in the epidermis and could promote epidermal barrier recovery.Methods: To address the abovementioned issue, we explored the antioxidative property of honey/chamomile extract by using non-cell-based KEAP1-inhibition assay and cultured human epidermal keratinocytes.Results: Herein we report that the extract inhibited KEAP1-NRF2 interaction and induced keratinocyte production of antioxidant small proline-rich protein.Conclusion: Our results may offer an opportunity to develop cosmetic products that boost NRF2-mediated antioxidative/antiaging, epidermis-intrinsic bio-responses.Keywords: NRF2, honey, chamomile, keratinocyte