Inhibition of protein tyrosine phosphatase 1B by diterpenoids isolated from Acanthopanax koreanum.
Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a therapy to treat type 2 diabetes and obesity. In our preliminary screening study on the PTP1B inhibitory activity, a CH2Cl2-soluble extract of the roots of Acanthopanax koreanum (Araliaceae) was found to inhibit PTP1B activity at 30 microg/ml. Eight diterpenoids were isolated from the active fraction and were evaluated for their inhibitory effect on PTP1B. A kaurane-type diterpene, 16alphaH,17-isovaleryloxy-ent-kauran-19-oic acid (7), inhibited PTP1B with an IC50 value of 7.1+/-0.9 microM in a non-competitive manner. Acanthoic acid (2) and ent-kaur-16-en-19-oic acid (5) also inhibited PTP1B in dose-dependent manners. Either introduction of a hydroxyl group or reduction of a carboxyl group at C-19 in pimarane-type to alcohol abolished the inhibitory effects toward PTP1B.
Korea Research Institute of Bioscience and Biotechnology, 52 Eoun-dong, Yuseong-gu, Daejeon 305-333, Republic of Korea.
MinKyun
M
Na
Won Keun
WK
Oh
Young Ho
YH
Kim
Xing Fu
XF
Cai
SoHee
S
Kim
Bo Yeon
BY
Kim
Jong Seog
JS
Ahn
D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D028001:Eleutherococcus / Q000737:chemistry*; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004224:Diterpenes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases