Helenalin from Centipeda minima ameliorates acute hepatic injury by protecting mitochondria function, activating Nrf2 pathway and inhibiting NF-κB activation.
Biomed Pharmacother
; 119: 109435, 2019 Nov.
Article
in En
| MEDLINE
| ID: mdl-31520915
ABSTRACT
Acute liver injury is a life-threatening syndrome that often caused by hepatocyte damage and is characterized by inï¬ammatory and oxidative responses. Helenalin isolated from Centipeda minima (HCM) has been found to have anti-inflammatory and anti-oxidative effects. Here, this study aimed to investigate the effects and underlying mechanisms of HCM on Lipopolysaccharide/D-Galactosamine (LPS/D-GalN)-induced acute liver injury. Mice were intragastrically administered with various dose of HCM for 10 days; 2â¯h after the final treatment, the mice were injected with 50⯵g/kg LPS and 800â¯mg/kg D-GalN. The histopathological changes, hepatocyte apoptosis, serum cytokines, oxidative stress and inflammatory cytokines were assessed. The results showed that HCM signiï¬cantly ameliorated the hepatic injury, as evidenced by the attenuation of histopathological changes and the decrease in serum aminotransferase and total bilirubin activities. HCM markedly decreased hepatocyte apoptosis by modulating the mitochondria-dependent pathway, including the increase in the Bcl-2/Bax ratio, the inhibition of caspase-3, -8 and -9, and the inhibition of cytochrome C release. Moreover, HCM strongly alleviated oxidative stress, lipid peroxidation and reactive oxygen species (ROS) generation by activating the Nrf2 signaling pathway. In addition, HCM signiï¬cantly attenuated inflammatory cytokines including TNF-α, IL6 and IL-1ß as well as NO production by inhibiting TLR4 signaling transduction and NF-κB activation. In conclusion, HCM protects hepatocytes from damage induced by LPS/D-GalN, which may contribute to its ability to alleviate hepatocyte apoptosis by protecting the mitochondrial function, inhibit oxidative stress by activating the Nrf2 pathway, and attenuate inflammation by inhibiting NF-κB activation. This study demonstrates that HCM may be developed as a potential agent for the treatment of acute liver failure.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
NF-kappa B
/
Protective Agents
/
Sesquiterpenes, Guaiane
/
NF-E2-Related Factor 2
/
Liver
/
Mitochondria
Limits:
Animals
Language:
En
Journal:
Biomed Pharmacother
Year:
2019
Document type:
Article
Affiliation country:
China