Introduction: 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.
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