Bioactive compound schaftoside from Clinacanthus nutans attenuates acute liver injury by inhibiting ferroptosis through activation the Nrf2/GPX4 pathway.
J Ethnopharmacol
; 328: 118135, 2024 Jun 28.
Article
em En
| MEDLINE
| ID: mdl-38556139
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Clinacanthus nutans (Burm. f.) Lindau, a traditional herb renowned for its anti-tumor, antioxidant, and anti-inflammatory properties, has garnered considerable attention. Although its hepatoprotective effects have been described, there is still limited knowledge of its treatment of acute liver injury (ALI), and its mechanisms remain unclear. AIM OF THE STUDY To assess the efficacy of Clinacanthus nutans in ALI and to identify the most effective fractions and their underlying mechanism of action. METHODS:
Bioinformatics was employed to explore the underlying anti-hepatic injury mechanisms and active compounds of Clinacanthus nutans. The binding ability of schaftoside, a potential active ingredient in Clinacanthus nutans, to the core target nuclear factor E2-related factor 2 (Nrf2) was further determined by molecular docking. The role of schaftoside in improving histological abnormalities in the liver was observed by H&E and Masson's staining in an ALI model induced by CCl4. Serum and liver biochemical parameters were measured using AST, ALT and hydroxyproline kits. An Fe2+ kit, transmission electron microscopy, western blotting, RT-qPCR, and DCFH-DA were used to measure whether schaftoside reduces ferroptosis-induced ALI. Subsequently, specific siRNA knockdown of Nrf2 in AML12 cells was performed to further elucidate the mechanism by which schaftoside attenuates ferroptosis-induced ALI.RESULTS:
Bioinformatics analysis and molecular docking showed that schaftoside is the principal compound from Clinacanthus nutans. Schaftoside was shown to diminish oxidative stress levels, attenuate liver fibrosis, and forestall ferroptosis. Deeper investigations revealed that schaftoside amplified Nrf2 expression and triggered the Nrf2/GPX4 pathway, thereby reversing mitochondrial aberrations triggered by lipid peroxidation, GPX4 depletion, and ferroptosis.CONCLUSION:
The lead compound schaftoside counters ferroptosis through the Nrf2/GPX4 axis, providing insights into a novel molecular mechanism for treating ALI, thereby presenting an innovative therapeutic strategy for ferroptosis-induced ALI.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acanthaceae
/
Ferroptose
/
Glicosídeos
Idioma:
En
Revista:
J Ethnopharmacol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China