acyclic triterpenoids from alpinia katsumadai inhibit IL-6-induced STAT3 Activation

The seeds of Alpinia katsumadai yielded two new acyclic triterpenoids, 2,3,6,22,23 -pentahydroxy -2,6,11,15,19,23-hexamethyl-tetracosa-7,10,14,18-tetraene (3) and 2,3,6,22,23 -pentahydroxy-2,10,15,19,23-hexamethyl-7-methylenetetracosa-10,14,18-triene (4), as well as two known compounds, 2,3,22,23-tertrahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (1) and 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (2). The absolute configurations of 2 and 3, which were determined by means of a modified Mosher’s method, are suggested as (3R; 5S; 22R) and (3R; 22R), respectively. Compounds 1–4 inhibited IL-6-induced JAK2/STAT3 activity in a dose-dependent fashion, with IC₅₀ values of 0.67, 0.71, 2.18, and 2.99 µM. Moreover, IL-6-stimulated phosphorylation of STAT3 was significantly suppressed in U266 cells by the administration of A. katsumadai EtOH extract and Compounds 1 and 2. These results suggest that major phytochemicals, Compounds 1 and 2, obtained from A. katsumadai may be useful candidates for designing new IL-6 inhibitors as anti-inflammatory agents.