Biomol Ther.  2017 Jul;25(4):427-433. 10.4062/biomolther.2016.112.

Galangin Activates the ERK/AKT-Driven Nrf2 Signaling Pathway to Increase the Level of Reduced Glutathione in Human Keratinocytes

• Hewage SR
• Piao MJ
• Kang KA
• Ryu YS
• Fernando P
• Oh MC
• Park JE
• Shilnikova K
• Moon YJ
• Shin DO
• Hyun JW

• KMID: 2386910
• DOI: http://doi.org/10.4062/biomolther.2016.112

Abstract

Previously, we demonstrated that galangin (3,5,7-trihydroxyflavone) protects human keratinocytes against ultraviolet B (UVB)-induced oxidative damage. In this study, we investigated the effect of galangin on induction of antioxidant enzymes involved in synthesis of reduced glutathione (GSH), and investigated the associated upstream signaling cascades. By activating nuclear factor-erythroid 2-related factor (Nrf2), galangin treatment significantly increased expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS). This activation of Nrf2 depended on extracellular signal-regulated kinases (ERKs) and protein kinase B (AKT) signaling. Inhibition of GSH in galangin-treated cells attenuated the protective effect of galangin against the deleterious effects of UVB. Our results reveal that galangin protects human keratinocytes by activating ERK/AKT-Nrf2, leading to elevated expression of GSH-synthesizing enzymes.

Keyword

Galangin; Reduced glutathione; Nuclear factor-erythroid 2-related factor; Glutamate-cysteine ligase catalytic subunit; Glutathione synthetase

MeSH Terms

Catalytic Domain
Extracellular Signal-Regulated MAP Kinases
Glutamate-Cysteine Ligase
Glutathione Synthase
Glutathione*
Humans*
Keratinocytes*
Proto-Oncogene Proteins c-akt
Extracellular Signal-Regulated MAP Kinases
Glutamate-Cysteine Ligase
Glutathione
Glutathione Synthase
Proto-Oncogene Proteins c-akt