TY - JOUR
T1 - Flindissone, a Limonoid Isolated from Trichilia prieuriana, Is an LXR Agonist
AU - Resetar, Mirta
AU - Tietcheu Galani, Borris R.
AU - Tsamo, Armelle T.
AU - Chen, Ya
AU - Schachner, Daniel
AU - Stolzlechner, Stefanie
AU - Mawouma Pagna, Julio I.
AU - Beniddir, Mehdi A.
AU - Kirchmair, Johannes
AU - Dirsch, Verena M.
N1 - Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society and American Society of Pharmacognosy.
PY - 2023/8/25
Y1 - 2023/8/25
N2 - In this study, the ability of six limonoids from Trichilia prieuriana (Meliaceae) to activate the liver X receptor (LXR) was assessed. One of these limonoids, flindissone, was shown to activate LXR by reporter-gene assays. Flindissone is a ring-intact limonoid, structurally similar to sterol-like LXR ligands. In endogenous cellular settings, flindissone showed an activity profile that is characteristic of LXR agonists. It induced cholesterol efflux in THP-1 macrophages by increasing the cholesterol transporter ABCA1 and ABCG1 gene expression. In HepG2 cells, flindissone induced the expression of IDOL, an LXR-target gene that is associated with the downregulation of the LDL receptor. However, unlike synthetic and similarly to sterol-based LXR agonists, flindissone did not induce the expression of the SREBP1c gene, a major transcription factor regulating de novo lipogenesis. Additionally, flindissone also appeared to be able to inhibit post-translational activation of SREBP1c. The results presented here reveal a natural product as a new LXR agonist and point to an additional property of T. prieuriana and other plant extracts containing flindissone.
AB - In this study, the ability of six limonoids from Trichilia prieuriana (Meliaceae) to activate the liver X receptor (LXR) was assessed. One of these limonoids, flindissone, was shown to activate LXR by reporter-gene assays. Flindissone is a ring-intact limonoid, structurally similar to sterol-like LXR ligands. In endogenous cellular settings, flindissone showed an activity profile that is characteristic of LXR agonists. It induced cholesterol efflux in THP-1 macrophages by increasing the cholesterol transporter ABCA1 and ABCG1 gene expression. In HepG2 cells, flindissone induced the expression of IDOL, an LXR-target gene that is associated with the downregulation of the LDL receptor. However, unlike synthetic and similarly to sterol-based LXR agonists, flindissone did not induce the expression of the SREBP1c gene, a major transcription factor regulating de novo lipogenesis. Additionally, flindissone also appeared to be able to inhibit post-translational activation of SREBP1c. The results presented here reveal a natural product as a new LXR agonist and point to an additional property of T. prieuriana and other plant extracts containing flindissone.
UR - http://www.scopus.com/inward/record.url?scp=85167810069&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.3c00059
DO - 10.1021/acs.jnatprod.3c00059
M3 - Article
C2 - 37526502
AN - SCOPUS:85167810069
VL - 86
SP - 1901
EP - 1909
JO - Journal of Natural Products
JF - Journal of Natural Products
SN - 0163-3864
IS - 8
ER -