TY - JOUR
T1 - A stilbene dimer and flavonoids from the aerial parts of Chromolaena odorata with proprotein convertase subtilisin/kexin type 9 expression inhibitory activity
AU - Pel, Pisey
AU - Chae, Hee Sung
AU - Nhoek, Piseth
AU - Kim, Young Mi
AU - Khiev, Piseth
AU - Kim, Geum Jin
AU - Nam, Joo Won
AU - Choi, Hyukjae
AU - Choi, Young Hee
AU - Chin, Young Won
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/6
Y1 - 2020/6
N2 - Investigation of components of the chloroform-soluble and ethyl acetate-soluble extracts of the aerial parts of Chromolaena odorata L. selected by PCSK9 mRNA expression monitoring assay in HepG2 cells led to the isolation of a new stilbene dimer, (+)-8b-epi-ampelopsin A (1), and 30 known compounds (2–31). The structures of the isolates were established by interpretation of NMR spectroscopic data and the stereochemistry of the new stilbene (1) was proposed based on ECD and NMR calculations. Among the isolates, 1, 5,6,7,4′-tetramethoxyflavanone (6), 5,6,7,3′,4′-pentamethoxyflavanone (7), acacetin (18), and uridine (21) were found to inhibit PCSK9 mRNA expression with IC50 values of 20.6, 21.4, 31.7, 15.0, and 13.7 µM, respectively. Furthermore, the most abundant isolate among the selected compounds, 6, suppressed PCSK9 and low-density lipoprotein receptor protein expression in addition to downregulating the mRNA expression of HNF-1α.
AB - Investigation of components of the chloroform-soluble and ethyl acetate-soluble extracts of the aerial parts of Chromolaena odorata L. selected by PCSK9 mRNA expression monitoring assay in HepG2 cells led to the isolation of a new stilbene dimer, (+)-8b-epi-ampelopsin A (1), and 30 known compounds (2–31). The structures of the isolates were established by interpretation of NMR spectroscopic data and the stereochemistry of the new stilbene (1) was proposed based on ECD and NMR calculations. Among the isolates, 1, 5,6,7,4′-tetramethoxyflavanone (6), 5,6,7,3′,4′-pentamethoxyflavanone (7), acacetin (18), and uridine (21) were found to inhibit PCSK9 mRNA expression with IC50 values of 20.6, 21.4, 31.7, 15.0, and 13.7 µM, respectively. Furthermore, the most abundant isolate among the selected compounds, 6, suppressed PCSK9 and low-density lipoprotein receptor protein expression in addition to downregulating the mRNA expression of HNF-1α.
KW - (+)-8b-epi-ampelopsin A
KW - 5,6,7,4′- tetramethoxyflavanone
KW - Chromolaena odorata
KW - Flavonoid
KW - HNF-1α
KW - LDLR
KW - PCSK9
KW - Stilbene dimer
UR - http://www.scopus.com/inward/record.url?scp=85083676314&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2020.103869
DO - 10.1016/j.bioorg.2020.103869
M3 - Article
C2 - 32335358
AN - SCOPUS:85083676314
SN - 0045-2068
VL - 99
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
M1 - 103869
ER -