Aqueous Extraction of Citrus unshiu Peel Induces Proangiogenic Effects Through the FAK and ERK1/2 Signaling Pathway in Human Umbilical Vein Endothelial Cells.
Citrus unshiu peel has been used empirically as a traditional medicine to improve bronchial asthma and blood circulation in northeast Asian nations, including Korea, Japan, and China. In this study, we report the proangiogenic effects of the aqueous extract of Citrus unshiu peel (AECUP). In human umbilical vein endothelial cells, AECUP significantly induced cellular migration and capillary tube formation. We also demonstrated that AECUP markedly increased the phosphorylation of FAK and ERK1/2 through the integrin signaling pathway. Additionally, we identified that narirutin and hesperidin were major constituents of AECUP and both showed proangiogenic effects, but at different levels. Collectively, these results suggest that the AECUP may have potential as a therapeutic agent for improving angiogenic functions with reduced harmful side effects.
1 Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University , Jeju-do, Korea.
Jungwhoi
J
Lee
1 Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University , Jeju-do, Korea.
Dong-Shik
DS
Yang
1 Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University , Jeju-do, Korea.
Song-I
SI
Han
1 Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University , Jeju-do, Korea.
Jeong Hun
JH
Yun
1 Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University , Jeju-do, Korea.
Il-Woong
IW
Kim
2 Division of Strategic Research Planning and Assessment, Korea Research Institute of Bioscience & Biotechnology , Daejeon, Republic of Korea .
Seung Jun
SJ
Kim
1 Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University , Jeju-do, Korea.|3 Subtropical/Tropical Organism Gene Bank, Jeju National University , Jeju, Korea.
Jae Hoon
JH
Kim
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D002957:Citrus / Q000737:chemistry*; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D005638:Fruit / Q000737:chemistry; D006569:Hesperidin / Q000737:chemistry / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D043925:Angiogenesis Inducing Agents; D004187:Disaccharides; D044950:Flavanones; D010936:Plant Extracts; C500601:narirutin; D006569:Hesperidin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
Citrus unshiu peel; ERK1/2; FAK; angiogenesis; hesperidin