20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol, a metabolite of ginsenoside Rb1, enhances the production of hyaluronic acid through the activation of ERK and Akt mediated by Src tyrosin kinase in human keratinocytes.
The aim of the present study was to determine the mechanisms through which 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (20GPPD) promotes the production of hyaluronic acid (HA) in human keratinocytes. 20GPPD is the primary bioactive metabolite of Rb1, a major ginsenoside found in ginseng (Panax ginseng). We sought to elucidate the underlying mechanisms behind the 20GPPD-induced production of HA. We found that 20GPPD induced an increase in HA production by elevating hyaluronan synthase 2 (HAS2) expression in human keratinocytes. The phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was also enhanced by 20GPPD in a dose-dependent manner. The pharmacological inhibition of ERK (using U0126) or Akt (using LY294002) suppressed the 20GPPD-induced expression of HAS2, whereas treatment with an epidermal growth factor receptor (EGFR) inhibitor (AG1478) or an intracellular Ca2+ chelator (BAPTA/AM) did not exert any observable effects. The increased Src phosphorylation was also confirmed following treatment with 20GPPD in the human keratinocytes. Following pre-treatment with the Src inhibitor, PP2, both HA production and HAS2 expression were attenuated. Furthermore, the 20GPPD-enhanced ERK and Akt signaling decreased following treatment with PP2. Taken together, our results suggest that Src kinase plays a critical role in the 20GPPD-induced production of HA by acting as an upstream modulator of ERK and Akt activity in human keratinocytes.
Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.
Tae-Gyu
TG
Lim
Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.
Ae Ji
AJ
Jeon
Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
Ji Hye
JH
Yoon
WCU Biomodulation Major, Department of Agricultural Biotechnology and Institute on Aging, Seoul National University, Seoul 151-921, Republic of Korea.
Dasom
D
Song
WCU Biomodulation Major, Department of Agricultural Biotechnology and Institute on Aging, Seoul National University, Seoul 151-921, Republic of Korea.
Jong-Eun
JE
Kim
Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.
Jung Yeon
JY
Kwon
Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.
Jong Rhan
JR
Kim
School of Food Science and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
Nam Joo
NJ
Kang
Skin Research Institute, Amorepacific Corporation R&D Center, Yongin 341-1, Republic of Korea.
Jun-Seong
JS
Park
Skin Research Institute, Amorepacific Corporation R&D Center, Yongin 341-1, Republic of Korea.
Myeong Hun
MH
Yeom
Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
Deok-Kun
DK
Oh
Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
Yoongho
Y
Lim
Department of Food Science, Cornell University, Ithaca, NY 14850, USA.
Charles C
CC
Lee
Department of Food Science, Cornell University, Ithaca, NY 14850, USA.
Chang Yong
CY
Lee
Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea.
Ki Won
KW
Lee
D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D036145:Ginsenosides / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012502:Sapogenins / Q000494:pharmacology*; D019061:src-Family Kinases / Q000378:metabolism*
D036145:Ginsenosides; D012502:Sapogenins; C442759:ginsenoside Rb1; D006820:Hyaluronic Acid; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C062916:protopanaxadiol