Identification of chromomoric acid C-I as an Nrf2 activator in Chromolaena odorata.
Activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) contributes to several beneficial bioactivities of natural products, including induction of an increased cellular stress resistance and prevention or resolution of inflammation. In this study, the potential of a crude leaf extract of Chromolaena odorata, traditionally used against inflammation and skin lesions, was examined for Nrf2 activation. Guided by an Nrf2-dependent luciferase reporter gene assay, the phytoprostane chromomoric acid C-I (1) was identified as a potent Nrf2 activator from C. odorata with a CD (concentration doubling the response of vehicle-treated cells) of 5.2 μM. When tested at 1-10 μM, 1 was able to induce the endogenous Nrf2 target gene heme oxygenase 1 (HO-1) in fibroblasts. Between 2 and 5 μM, compound 1 induced HO-1 in vascular smooth muscle cells (VSMC) and inhibited their proliferation in a HO-1-dependent manner, without eliciting signs of cytotoxicity.
Department of Pharmacogosy, University of Vienna , Althanstrasse 14, 1090 Vienna, Austria.
Elke H
EH
Heiss
Thi Van Anh
TV
Tran
Kristin
K
Zimmermann
Stefan
S
Schwaiger
Corina
C
Vouk
Barbara
B
Mayerhofer
Clemens
C
Malainer
Atanas G
AG
Atanasov
Hermann
H
Stuppner
Verena M
VM
Dirsch
D018929:Cell Culture Techniques; D002470:Cell Survival; D036604:Chromolaena / Q000737:chemistry* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007249:Inflammation; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry; D014744:Vietnam
D005231:Fatty Acids, Unsaturated; D005663:Furans; D051267:NF-E2-Related Factor 2; C000589236:chromomoric acid C-I; D008156:Luciferases; D051547:Heme Oxygenase-1