Protective effects of ginsenoside F2 on 12-O-tetradecanoylphorbol-13-acetate-induced skin inflammation in mice.
Topical use of ginsenosides, the major bioactive substances in Panax ginseng, has been used for the treatment of irritated skin complaints. However, the protective mechanisms of ginsenosides remain unclear. In the present study, we investigated the anti-inflammatory role of ginsenoside F2 (GF2) on the skin inflammation. To induce irritant dermatitis, 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied on the surface of the mouse ears with or without treatments of GF2 and dexamethasone for 24 h. Protective effects of GF2 on edema and inflammation were assessed by measuring ear thickness, weights of skin punch, and inflammatory responses. In gross findings, treatments with GF2 significantly decreased skin thickness and weight compared to those of TPA-treated groups, which was comparable with the protective effects of dexamethasone. In addition, expression of inflammatory mediators was remarkably reduced in GF2-treated ears compared to that of vehicle-treated ears of mice. Interestingly, immunohistochemistry and flow cytometry analyses revealed that TPA treatment significantly increased infiltration of interleukin-17 (IL-17) producing dermal γδ T cells, while frequencies of γδ T cells was decreased by GF2 treatment, subsequently ameliorating inflammation in skin. Concomitantly, TPA-mediated skin inflammation was significantly ameliorated in IL-17A knock out mice. Furthermore, GF2 treatment inhibited infiltration and generation of reactive oxygen species (ROS) of neutrophils in damaged ears compared with vehicle-treated mice. These results clearly suggest that GF2 treatment ameliorates TPA-induced dermal inflammation by inhibiting production of IL-17 and ROS in γδ T cells and neutrophils, respectively. Therefore, as a natural compound, application of GF2 may be a novel therapeutic approach for treating skin inflammation.
The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Seol-Hee
SH
Park
Laboratory of Liver Research, KAIST, Daejeon, Republic of Korea.
Wonhyo
W
Seo
Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Hyuk Soo
HS
Eun
Laboratory of Liver Research, GSMSE, KAIST, Daejeon, Republic of Korea.
So Yeon
SY
Kim
Laboratory of Liver Research, GSMSE, KAIST, Daejeon, Republic of Korea.
Eunjung
E
Jo
Laboratory of Liver Research, GSMSE, KAIST, Daejeon, Republic of Korea.
Myung-Ho
MH
Kim
Laboratory of Liver Research, GSMSE, KAIST, Daejeon, Republic of Korea.
Won-Mook
WM
Choi
Laboratory of Liver Research, GSMSE, KAIST, Daejeon, Republic of Korea.
Jun-Hee
JH
Lee
Laboratory of Liver Research, GSMSE, KAIST, Daejeon, Republic of Korea.
Young-Ri
YR
Shim
Intelligent Synthetic Biology Center, KAIST, Daejeon, 34141, Republic of Korea.
Chang-Hao
CH
Cui
Department of Biological Sciences, KAIST, Daejeon, 34141, Republic of Korea; Intelligent Synthetic Biology Center, KAIST, Daejeon, 34141, Republic of Korea.
Sun Chang
SC
Kim
The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Cheol Yong
CY
Hwang
Laboratory of Liver Research, GSMSE, KAIST, Daejeon, Republic of Korea. Electronic address: wijeong@kaist.ac.kr.
Won-Il
WI
Jeong
D000279:Administration, Cutaneous; D000818:Animals; D003872:Dermatitis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004431:Ear, External / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D036145:Ginsenosides; D020381:Interleukin-17; D020011:Protective Agents; D017382:Reactive Oxygen Species; D016692:Receptors, Antigen, T-Cell, gamma-delta; C407883:ginsenoside F2; D013755:Tetradecanoylphorbol Acetate
Interleukin-17; Neutrophil; ROS; γδ T cell