Isoliquiritigenin alleviates LPS/ D-GalN-induced acute liver failure by activating the PGC-1α/ Nrf2 pathway to reduce oxidative stress and inflammatory response

Sep 23, 2021International immunopharmacology

Isoliquiritigenin may reduce sudden liver failure by activating protective pathways that lower oxidative stress and inflammation

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Isoliquiritigenin (ISL) significantly improved liver pathological changes in acute liver failure models.

ISL reduced oxidative stress by altering the expression of several key proteins in damaged liver cells.
The treatment decreased the levels of inflammation-related genes associated with liver damage.
ISL alleviated apoptosis in liver cells by increasing the Bcl-2/Bax ratio and suppressing cleaved caspase-3.
Evidence suggests that the protective effects of ISL may involve the PGC-1α/Nrf2 signaling pathway.
These findings indicate potential therapeutic avenues for acute liver failure treatment.

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Acute liver failure (ALF) is a dramatic liver disease characterized by large areas of inflammation. However, there are no available effective targeted drugs for ALF treatment. In the study, serum biochemical index and H&E were used to explore the amelioration of the liver histopathological changes. The oxidative stress kits, quantitative real-time PCR, western blot, immunohistochemistry, immunofluorescence staining, reactive oxygen species (ROS), and siRNA were used to elucidate the mechanisms underlying isoliquiritigenin (ISL) protection. The results showed that ISL significantly improved the liver pathological changes. Furthermore, ISL reduced oxidative stress by altering the expression of PGC-1α, Nrf2, HO-1, NQO1, Keap1, GCLC, and GCLM in damaged hepatocytes. Moreover, the levels of inflammation-related genes including NLRP3 inflammasome, IL-1β, IL-6, TNF-α, iNOS, and Mip-2 were repressed by ISL. In addition, ISL alleviated LPS/D-GalN-induced hepatocytes apoptosis by increasing the Bcl-2/Bax ratio and suppressing the expression of cleaved caspase-3. Further in vivo and in vitro evidence proved the involvement of the PGC-1α/Nrf2 signaling pathway in ISL protection. In conclusion, ISL improves the ability of anti-oxidative stress, alleviates inflammatory reaction, apoptosis, and inhibits NLRP3 inflammasome to protect lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF through activating the PGC-1α/Nrf2 pathway, which provides the possibility for the treatment of ALF.

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Isoliquiritigenin alleviates LPS/ D-GalN-induced acute liver failure by activating the PGC-1α/ Nrf2 pathway to reduce oxidative stress and inflammatory response

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