title: Inhibition of protein tyrosine phosphatase 1beta by hispidin derivatives isolated from the fruiting body of Phellinus linteus.
abstract: Protein tyrosine phosphatase 1beta (PTP1beta) acts as a negative regulator of insulin signaling. Selective inhibition of PTP1beta has served as a potential drug target for the treatment of type 2 diabetes mellitus. We evaluated the inhibitory effect of Phellinus linteus against PTP1beta as part of our ongoing search for natural therapeutic and preventive agents for diabetes mellitus. Fractions of the P. linteus extract were found to exhibit significant inhibitory activities against PTP1beta. In an attempt to identify bioactive components, we isolated, from the most active ethyl acetate fraction, five hispidin derivatives (phelligridimer A, davallialactone, hypholomine B, interfungins A, and inoscavin A) and four phenolic compounds (protocatechuic acid, protocatechualdehyde, caffeic acid, and ellagic acid). The chemical structures of these compounds were elucidated from spectroscopic evidence and by comparison with published data. All the compounds strongly inhibited PTP1beta activity in an in vitro assay; their IC50 values ranged from 9.0 +/- 0.01 to 58.2 +/- 0.3 microM. Our results indicated that the hispidin skeleton may be an important moiety for inhibitory activity of the above compounds against PTP1beta. Thus, hispidin derivatives could be a potent new class of natural PTP1beta inhibitors.
authors.affiliation: Center for Efficacy Assessment and Development of Functional Foods and Drugs, Regional Innovation Center, Hallym University, Chuncheon, 200-702 Gangwon-do, South Korea.
authors.forename: Yeon Sil
authors.initials: YS
authors.lastname: Lee
authors.forename: Il-Jun
authors.initials: IJ
authors.lastname: Kang
authors.forename: Moo Ho
authors.initials: MH
authors.lastname: Won
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Jin Kyu
authors.initials: JK
authors.lastname: Kim
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
mesh_terms: D005638:Fruit / Q000737:chemistry; D000084682:Phellinus; D010936:Plant Extracts; D011134:Polysaccharides / Q000737:chemistry*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D011753:Pyrones / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C526145:Phellinus linteus extract; D010936:Plant Extracts; D011134:Polysaccharides; D011753:Pyrones; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C007946:hispidin