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In vitro and in vivo structure and activity relationship analysis of polymethoxylated flavonoids: Identifying sinensetin as a novel antiangiogenesis agent
- Source :
- Molecular Nutrition & Food Research. 56:945-956
- Publication Year :
- 2012
- Publisher :
- Wiley, 2012.
-
Abstract
- Scope Polymethoxylated flavonoids are present in citrus fruit in a range of chemical structures and abundance. These compounds have potential for anticarcinogenesis, antitumor, and cardiovascular protective activity, but the effect on angiogenesis has not been well studied. Methods and results Human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish (Danio rerio) in vivo models were used to screen and identify the antiangiogenesis activity of seven polymethoxylated flavonoids; namely, hesperetin, naringin, neohesperidin, nobiletin, scutellarein, scutellarein tetramethylether, and sinensetin. Five, excluding naringin and neohesperidin, showed different degrees of potency of antiangiogenesis activity. Sinensetin, which had the most potent antiangiogenesis activity and the lowest toxicity, inhibited angiogenesis by inducing cell cycle arrest in the G0/G1 phase in HUVEC culture and downregulating the mRNA expressions of angiogenesis genes flt1, kdrl, and hras in zebrafish. Conclusion The in vivo structure–activity relationship (SAR) analysis indicated that a flavonoid with a methoxylated group at the C3′ position offers a stronger antiangiogenesis activity, whereas the absence of a methoxylated group at the C8 position offers lower lethal toxicity in addition to enhancing the antiangiogenesis activity. This study provides new insight into how modification of the chemical structure of polymethoxylated flavonoids affects this newly identified antiangiogenesis activity.
- Subjects :
- Down-Regulation
Angiogenesis Inhibitors
Oncogene Protein p21(ras)
Pharmacology
Biology
Methylation
Resting Phase, Cell Cycle
Nobiletin
Animals, Genetically Modified
Structure-Activity Relationship
chemistry.chemical_compound
In vivo
Human Umbilical Vein Endothelial Cells
Animals
Humans
Structure–activity relationship
RNA, Messenger
Sinensetin
Naringin
Cells, Cultured
Zebrafish
Cell Proliferation
Flavonoids
Neohesperidin
Scutellarein
fungi
Hesperetin
Zebrafish Proteins
Receptors, Vascular Endothelial Growth Factor
chemistry
Biochemistry
Blood Vessels
Biological Assay
Food Science
Biotechnology
Subjects
Details
- ISSN :
- 16134125
- Volume :
- 56
- Database :
- OpenAIRE
- Journal :
- Molecular Nutrition & Food Research
- Accession number :
- edsair.doi.dedup.....5e83d691dc8f58752fffbf41d322696e