Anti-angiogenic effects of Shiraiachrome A, a compound isolated from a Chinese folk medicine used to treat rheumatoid arthritis.

Abstract

The Chinese folk medicine Shiraia bambusicola has long been utilized in the treatment of rheumatoid arthritis, a disease in which angiogenesis plays an important role. We report here the isolation of the compound Shiraiachrome A from S. bambusicola and the demonstration of its anti-angiogenic properties. We found that Shiraiachrome A significantly inhibited the proliferation, migration, and tube formation of human microvascular endothelial cells (HMEC) in a dose-dependent manner, with average IC(50) values of 2.1+/-0.36, 1.97+/-0.44, and 1.65+/-0.59 microM, respectively. In addition, Shiraiachrome A inhibited the formation of new microvessels in a rat aorta culture model as well as in the chick embryo chorioallantoic membrane (CAM) assay. Investigation of the mechanism of action of Shiraiachrome A demonstrated that this compound suppressed the autophosphorylation of four receptor tyrosine kinases (RTKs), with IC(50) values ranging from 2.2 to 4.3 microM. These results suggest that Shiraiachrome A inhibits angiogenesis by blocking growth factor-stimulated autophosphorylation of RTKs. These findings also indicate that Shiraiachrome A may be a potent therapeutic agent for angiogenesis-related diseases such as cancer, rheumatoid arthritis, and diabetic retinopathy.

• Authors: Yunguang Tong, Xiongwen Zhang, Weimin Zhao, Yixiang Zhang, Jingyu Lang, Yuhua Shi, Wenfu Tan, Meihong Li, Yongwei Zhang, Linjiang Tong, He Lu, Liping Lin, Jian Ding
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 494 Issue 2-3 Pg. 101-9 (Jun 28 2004) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15212963 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Drugs, Chinese Herbal
• Indicators and Reagents
• Shiraiachrome A
• Perylene
• Receptor Protein-Tyrosine Kinases

Topics

• Angiogenesis Inhibitors (chemistry, isolation & purification, pharmacology)
• Animals
• Aorta, Thoracic (cytology, drug effects)
• Arthritis, Rheumatoid (drug therapy)
• Capillaries (drug effects, ultrastructure)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Chick Embryo
• Chorion (drug effects)
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (chemistry, pharmacology)
• Endothelial Cells (drug effects)
• Immunoblotting
• Indicators and Reagents
• Mice
• Microtubules (drug effects, ultrastructure)
• NIH 3T3 Cells
• Perylene (analogs & derivatives, chemistry, isolation & purification, pharmacology)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Receptor Protein-Tyrosine Kinases (metabolism)