Galangin Activates the ERK/AKT-Driven Nrf2 Signaling Pathway to Increase the Level of Reduced Glutathione in Human Keratinocytes.
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.
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Susara Ruwan Kumara
SRK
Madduma Hewage
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Mei Jing
MJ
Piao
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Kyoung Ah
KA
Kang
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Yea Seong
YS
Ryu
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Pattage Madushan Dilhara Jayatissa
PMDJ
Fernando
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Min Chang
MC
Oh
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Jeong Eon
JE
Park
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Kristina
K
Shilnikova
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Yu Jin
YJ
Moon
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Dae O
DO
Shin
School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea.
Jin Won
JW
Hyun
Galangin; Glutamate-cysteine ligase catalytic subunit; Glutathione synthetase; Nuclear factor-erythroid 2-related factor; Reduced glutathione