title: The natural compound n-butylidenephthalide derived from the volatile oil of Radix Angelica sinensis inhibits angiogenesis in vitro and in vivo.
abstract: Radix Angelica sinensis is a Chinese medicinal herb that has been used extensively in the East for the treatment of cardiovascular diseases (CVDs). Angiogenesis plays an important role in the pathogenesis of CVDs. We hypothesized that Radix A. sinensis may contain angiogenesis modulators. In the current study, we investigated the effects of a volatile oil of Radix A. sinensis (VOAS) and n-butylidenephthalide (BP), one of the bioactive components in VOAS, on angiogenesis in vitro and in vivo. The results suggested that VOAS exerted anti-angiogenic effects by inhibiting human umbilical vein endothelial cell proliferation, migration and capillary-like tube formation on Matrigel. BP was also shown to be anti-angiogenic and its mechanisms were through inhibition of cell cycle progression and induction of apoptosis. Western blotting analysis indicated that the anti-angiogenic actions of BP were associated with the activation of p38 and ERK 1/2 but not SAPK/JNK and Akt signaling pathways. Further investigations showed that BP inhibited endothelial sprouting in an ex vivo mouse aortic ring model and was a potent inhibitor of the development of zebrafish subintestinal vessels in vivo. Our data using the volatile oil contrast with previous findings, which showed an aqueous extract of Radix A. sinensis was pro-angiogenic. This highlights the importance of identifying pro- and anti-angiogenic substances in Radix A. sinensis, not only for the development of novel angiogenesis modulators for the treatment of CVDs, but also to ensure the proper use of Radix A. sinensis as a nutraceutical.
authors.affiliation: Department of Obstetrics and Gynecology, University of Cambridge, The Rosie Hospital, Cambridge, CB2 0SW, UK.
authors.forename: Ju-Ching
authors.initials: JC
authors.lastname: Yeh
authors.forename: Tereza
authors.initials: T
authors.lastname: Cindrova-Davies
authors.forename: Mirella
authors.initials: M
authors.lastname: Belleri
authors.forename: Lucia
authors.initials: L
authors.lastname: Morbidelli
authors.forename: Nigel
authors.initials: N
authors.lastname: Miller
authors.forename: Chin-Wen Chantal
authors.initials: CW
authors.lastname: Cho
authors.forename: Kelvin
authors.initials: K
authors.lastname: Chan
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Wang
authors.forename: Guo-An
authors.initials: GA
authors.lastname: Luo
authors.forename: Marina
authors.initials: M
authors.lastname: Ziche
authors.forename: Marco
authors.initials: M
authors.lastname: Presta
authors.forename: David Stephen
authors.initials: DS
authors.lastname: Charnock-Jones
authors.forename: Tai-Ping
authors.initials: TP
authors.lastname: Fan
mesh_terms: D029971:Angelica sinensis / Q000737:chemistry*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000254:growth & development; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007422:Intestines / Q000098:blood supply / Q000187:drug effects; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009822:Oils, Volatile / Q000737:chemistry*; D010796:Phthalic Anhydrides / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish
chemical_list: D001688:Biological Products; D009822:Oils, Volatile; D010796:Phthalic Anhydrides; C026105:butylidenephthalide