Inhibition of protein tyrosine phosphatase 1B by diterpenoids isolated from Acanthopanax koreanum.

摘要

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.