title: The anti-angiogenic effect of sinomenine.
abstract: Sinomenine is an alkaloid extracted from the Chinese medicinal plant, Sinomenium acutum, which has been utilized to treat rheumatoid arthritis (RA) in China for over 2000 years. Sinomenine has been shown to mediate a wide range of pharmacological actions which includes anti-inflammatory and anti-rheumatic effects. RA has been classified as a chronic immune-mediated disease that exhibits overlapping manifestation of inflammatory, abnormal cellular and hormonal immune responses with synovial hyperplasia. Since, angiogenesis is recognized to play a critical role in the development of RA and anti-angiogenic therapy has been proposed as a new therapeutic strategy for treatment of RA, we would like to see if sinomenine possesses anti-angiogenic property. In this study, sinomenine inhibited bFGF-induced proliferation of human umbilical vein endothelial cells (HUVEC) and arrested its cell cycle in G1 phase. Sinomenine disrupted tube formation of HUVEC on Matrigel and suppressed the chemotaxis of HUVEC. In addition, sinomenine reduced neovascularization in Matrigel plug assay as well as microvascular outgrowth in rat aorta ring sprouting assay. These results suggest that sinomenine inhibited bFGF-induced angiogenesis in vitro and in vivo. As the leukocytes-endothelial adhesive interactions also play an important role in inflammation, we found that sinomenine reduced the transmigration of granulocytic differentiated HL60 cells across IL-1beta activated HUVEC monolayer. Therefore, the inhibition of leukocytes migration across blood vessel walls and the anti-angiogenic effect of sinomenine may contribute towards its therapeutic mechanisms in alleviating the pathogenesis of RA.
authors.affiliation: Department of Biology, Science Faculty, Hong Kong Baptist University, Hong Kong.
authors.forename: T W
authors.initials: TW
authors.lastname: Kok
authors.forename: Patrick Y K
authors.initials: PY
authors.lastname: Yue
authors.forename: N K
authors.initials: NK
authors.lastname: Mak
authors.forename: T P D
authors.initials: TP
authors.lastname: Fan
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: Ricky N S
authors.initials: RN
authors.lastname: Wong
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D005346:Fibroblast Growth Factors; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009019:Morphinans / Q000494:pharmacology* / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D020533:Angiogenesis Inhibitors; D009019:Morphinans; D010936:Plant Extracts; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors; C009271:sinomenine