Acetyl barlerin from Barleria trispinosa induces chemopreventive NQO1 and attenuates LPS-induced inflammation: in vitro and molecular dynamic studies.
J Biomol Struct Dyn
; : 1-12, 2023 Dec 20.
Article
em En
| MEDLINE
| ID: mdl-38116740
ABSTRACT
Extraction and fractionation of Barleria trispinosa growing in Saudi Arabia yielded four iridoid compounds identified by spectroscopic techniques as acetylbarlerin (1), barlerin (2), shanzhiside methyl ester (3) and 6-âº-L-rhamnopyranosyl-8-O-acetylshanzihiside methyl ester (4). Preliminary experiments confirmed that compound 1 acts as an inducer of chemopreventive NAD(P)HQuinone oxidoreductase 1 (NQO1) enzymatic activity in a murine hepatoma (Hepa1c1c7) chemoprevention model. It also demonstrated the ability to inhibit the lipopolysaccharides (LPS)-induced nitric oxide (NO) production in the RAW264.7 macrophage model. Western blotting revealed the ability of compound 1 to up-regulate the protein expression of the NQO1 marker. Furthermore, compound 1 elicited NO suppression in RAW264.7 macrophages by inhibiting iNOS protein expression. Molecular docking and molecular simulation studies of 1 supported its experimental results as an inhibitor of the nuclear factor erythroid 2-Kelch-like ECH-associated protein 1 (Nrf2-KEAP1) complex, resulting in Nrf2-mediated induction of chemopreventive NQO1.Communicated by Ramaswamy H. Sarma.
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1
Bases de dados:
MEDLINE
Idioma:
En
Revista:
J Biomol Struct Dyn
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Arábia Saudita