Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing Activities.

Five new chalcones, 4,2',4'-trihydroxy-3'-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5-octadienyl]chalcone (1), (±)-4,2',4'-trihydroxy-3'-[(2E)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]chalcone (2), 4,2',4'-trihydroxy-3'-[(2E)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]chalcone (3), 2',3'-furano-4-hydroxy-4'-methoxychalcone (4), and (±)-4-hydroxy-2',3'-(2,3-dihydro-2-methoxyfurano)-4'-methoxychalcone (5), were isolated from the aerial parts of Angelica keiskei Koidzumi together with eight known chalcones, 6-13, which were identified as (±)-4,2',4'-trihydroxy-3'-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6), xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin (10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13), respectively. Chalcones 1-13 were evaluated for their promoter activity on heat shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 μM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas 1 did not induce any expression of these proteins. As a result, 6 seems to be a prospective HSP inducer.