Isolation of polyacetylenes with proprotein convertase/kexin type 9 downregulating activity and two new sesquiterpenes from the aerial parts of Aster koraiensis

Abstract

In this study, we aimed to isolate chemical compounds from the aerial parts of Aster koraiensis Nakai and to determine their proprotein convertase/kexin type 9 (PCSK9) mRNA expression inhibitory activities. Two new eudesmane-type sesquiterpenes, 1 beta,4 beta,13-trihydroxy-trans-eudesm-6-ene-1-O-beta-glucopyranoside (1) and 6 ''-O-(syringoyl)-1 beta,6 beta,9 beta,11-tetrahydroxy-trans-eudesm-3-en-6-O-beta-D-glucopyranoside (2), along with 20 known compounds were isolated. All the isolated structures were confirmed by measuring 1D and 2D NMR spectroscopic data and comparing with their reported values. Among the isolates, gymnasterkoreayne B (21) and gymnasterkoreayne E (22) exhibited potent inhibitory effects on PCSK9 expression with IC50 values of 47.9 and 42.9 mu M, respectively, and also increased LDLR expression. Our study provides insights into the use of these polyacetylenes or A. koraiensis extracts for cholesterol-lowering treatment. (C) 2020 Elsevier Ltd. All rights reserved.