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 μg/ml. Eight diterpenoids were isolated from the active fraction and were evaluated for their inhibitory effect on PTP1B. A kaurane-type diterpene, 16αH,17-isovaleryloxy-ent-kauran-19-oic acid (7), inhibited PTP1B with an IC50 value of 7.1 ± 0.9 μM 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.

Bioassay-guided fractionation of the CH2Cl2-soluble fraction led to the isolation of three PTP1B inhibitory diterpenoids, acanthoic acid (2), ent-kaur-16-en-19-oic acid (5), and 16αH,17-isovaleryloxy-ent-kauran-19-oic acid (7), along with their five derivatives.Figure optionsDownload as PowerPoint slide