Induction of hepatocyte growth factor production in human dermal fibroblasts and their proliferation by the extract of bitter melon pulp.
Hepatocyte growth factor (HGF) is useful as a potential therapeutic agent for hepatic and renal fibrosis and cardiovascular diseases through inducing proliferation of epithelial and endothelial cells. HGF inducers may also be useful as therapeutic agents for these diseases. However, there have been no reports on induction of HGF production by plant extracts or juices. An extract of bitter melon (Momordica charantia L.) pulp markedly induced HGF production. There was a time lag of 72 h before induction of HGF production after the extract addition. Its stimulatory effect was accompanied by upregulation of HGF gene expression. Increases in mitogen-activated protein kinases (MAPKs) were observed from 72 h after the extract addition. Inhibitors of MAPKs suppressed the extract-induced HGF production. The extract also stimulated cell proliferation. Both activities for induction of HGF production and cell proliferation were eluted together in a single peak with 14,000 Da on gel filtration. The results indicate that bitter melon pulp extract induced HGF production and cell proliferation of human dermal fibroblasts and suggest that activation of MAPKs is involved in the HGF induction. Our findings suggest potential usefulness of the extract for tissue regeneration and provide an insight into the molecular mechanism underlying the wound-healing property of bitter melon.
Ono
Takehiro
T
Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka, Okayama 700-8530, Japan.
Tsuji
Tomoe
T
Sakai
Miho
M
Yukizaki
Chizuko
C
Ino
Hisatoshi
H
Akagi
Isao
I
Hiramatsu
Kaori
K
Matsumoto
Yohsuke
Y
Sugiura
Yoshihiro
Y
Uto
Hirofumi
H
Tsubouchi
Hirohito
H
Gohda
Eiichi
E
D049109:Cell Proliferation; D019662:Cucurbitaceae / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D010936:Plant Extracts / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; D017228:Hepatocyte Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; C022616:thiazolyl blue