The stimulatory effects of Stewartia koreana extract on the proliferation and migration of fibroblasts and the wound healing activity of the extract in mice.
Stewartia koreana (S. koreana) has been used in the treatment of inflammatory diseases, such as acute gastroenteritis and aches, in Korean folk medicine and has been reported to have a number of biological activities, such as anti-inflammatory activity and the promotion of angiogenesis. In this study, we aimed to determine the effects of S. koreana extract (SKE) and its components on dermal fibroblast growth and migration, and to investigate the wound healing activity of the extract in mice. In vitro experiments revealed that the numbers of SKE-treated cells increased by approximately 2.5-‑ and 3.7-fold with 50 and 100 µg/ml of SKE, respectively. 5-bromo-2'-deoxy-uridine (BrdU) incorporation was also increased in the SKE-treated cells by 2.3-fold. SKE promoted the migration of human skin fibroblasts and, among the isolated compounds, hyperin increased the proliferation and migration of the fibroblasts to almost the same degree as SKE. Western blot analysis demonstrated that SKE stimulated the MEK/ERK1/2 and PI3K/Akt signaling pathways. In in vivo experiments, the SKE-treated wound lesions of mice decreased by approximately 7% in diameter after 2 days of treatment with SKE compared with the wound lesions on the 1st day of the experiment. On the 9th day of treatment, the diameter of the lesions was further reduced by approximately 83% in the SKE-treated wound areas compared with the wound areas on the 1st day of treatment. Our results demonstrate that methanol extracts of S. koreana leaves promote the proliferation and migration of skin fibroblasts and possess effective wound healing activity through the activation of the MEK/ERK1/2 and PI3K/Akt signaling pathways. Hyperin was identified as an active compound responsible for the stimulation of fibroblast growth and migration.
College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea.
Tae Hoon
TH
Lee
Graduate School of Biotechnology, Kyung Hee University, Yongin 446-701, Republic of Korea.
Guy Wilhem
GW
Lee
Graduate School of Biotechnology, Kyung Hee University, Yongin 446-701, Republic of Korea.
Keun Hyung
KH
Park
Graduate School of Biotechnology, Kyung Hee University, Yongin 446-701, Republic of Korea.
Mohamed Antar Aziz
MA
Mohamed
Graduate School of Biotechnology, Kyung Hee University, Yongin 446-701, Republic of Korea.
Myun Ho
MH
Bang
Graduate School of Biotechnology, Kyung Hee University, Yongin 446-701, Republic of Korea.
Yun Soo
YS
Baek
College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea.
Youngsook
Y
Son
College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea.
Dae Kyun
DK
Chung
College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea.
Nam-In
NI
Baek
College of Life Sciences, Kyung Hee University, Yongin 446-701, Republic of Korea.
Jiyoung
J
Kim
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System; D000432:Methanol; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012997:Solvents; D028242:Theaceae / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*
D005419:Flavonoids; D010936:Plant Extracts; D012997:Solvents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000432:Methanol