Planta Med 2014; 80(07): 557-560
DOI: 10.1055/s-0034-1368400
Biological and Pharmacological Activity
Letters
Georg Thieme Verlag KG Stuttgart · New York

Protein Tyrosine Phosphatase 1B Inhibitory Activity of Lavandulyl Flavonoids from Roots of Sophora flavescens

Tatsunori Sasaki
1  Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan
,
Wei Li
1  Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan
,
Koji Higai
1  Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan
,
Tran Hong Quang
2  College of Pharmacy, Chungnam National University, Daejeon, Korea
,
Young Ho Kim
2  College of Pharmacy, Chungnam National University, Daejeon, Korea
,
Kazuo Koike
1  Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Japan
› Author Affiliations
Further Information

Publication History

received 18 January 2014
revised 13 March 2014

accepted 18 March 2014

Publication Date:
29 April 2014 (online)

Abstract

Protein tyrosine phosphatase 1B is a non-transmembrane protein tyrosine phosphatase and major negative regulator in insulin signaling cascades, and much attention has been paid to protein tyrosine phosphatase 1B inhibitors as potential therapies for diabetes. The screening of a natural compound library led to the discovery of five lavandulyl flavonoids, which were isolated from the roots of Sophora flavescens, as novel PTP1B inhibitors: kuraridin (1), norkurarinone (2), kurarinone (3), 2′-methoxykurarinone (4), and kushenol T (5). The three most potent compounds, 1, 2, and 4 (IC50 < 30 µM), were demonstrated to be noncompetitive inhibitors of protein tyrosine phosphatase 1B based on a kinetic analysis, and they exhibited different inhibitory selectivities against four homologous protein tyrosine phosphatases (T cell protein tyrosine phosphatase, vaccinia H1-related phosphatase, and Src homology domain 2-containing protein tyrosine phosphatases 1 and 2). Compounds 1, 2, and 4 also exhibited cellular activity in the insulin signaling pathway by increasing the insulin-stimulated Akt phosphorylation level in human hepatocellular liver carcinoma HepG2 cells, suggesting their potential for new anti-insulin-resistant drug developments.