Iodized Garlic Extract Regulates Stress Responses in Epidermal Keratinocytes via the Transcription Factor Nrf2
Yuki Miyauchi, Natsumi Iwasaki, Liangjing Xie, Satoshi Yano, Taichi HaraABSTRACT
Objective
Garlic exerts protective effects against skin stress, including oxidative damage and trauma. Iodized garlic extract (IGEx) is a cosmetic ingredient developed through iodination of garlic odor components to achieve odor reduction. Although IGEx is expected to exhibit skin stress protection properties similar to garlic, the molecular mechanisms underlying the effects of IGEx on skin cells remain unclear. Therefore, this study comprehensively analyzed the effects of IGEx on human epidermal keratinocytes (HaCaT cells), with a particular focus on the stress response mechanisms.
Methods
Transcriptome analysis was conducted on HaCaT cells treated with IGEx. Nrf2 protein expression was assessed by western blotting, whereas target gene expression was evaluated by qRT‐PCR. Dehydrogenase activity was measured using Cell Counting Kit‐8. Functional analyses included hydrogen peroxide‐induced oxidative stress testing and in vitro wound healing assays, and pathway specificity was validated using Nrf2 knockout cells.
Results
IGEx increased Nrf2 protein expression 1.62‐fold and induced the expression of downstream target genes, including HMOX1 , AKR1C1 , and AKR1C3 . Additionally, intracellular NAD(P)H‐dependent dehydrogenase activity was enhanced in an Nrf2‐dependent manner. Furthermore, IGEx demonstrated protective effects against hydrogen peroxide toxicity and promoted wound healing.
Conclusion
IGEx activated Nrf2 and regulated stress responses in HaCaT cells. The control of intracellular NAD(P)H‐dependent dehydrogenase activity has been suggested to contribute to these effects. Additionally, the involvement of AHR was indicated, suggesting the coordinated regulation of Nrf2 in stress responses. This study provides a molecular foundation for the potential applications of IGEx as a cosmetic ingredient.