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

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

  • Int Immunopharmacol. 2021 Nov;100:108159. doi: 10.1016/j.intimp.2021.108159.
Lu Wang 1 Xiaohui Wang 1 Lina Kong 1 Shuyuan Wang 1 Kai Huang 2 Jingjing Wu 1 Changyuan Wang 1 Huijun Sun 1 Kexin Liu 1 Qiang Meng 3
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China.
  • 2 Drug Clinical Trial Institution, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, China.
  • 3 Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address: qiangmeng@dmu.edu.cn.
Abstract

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.

Keywords

Acute liver failure; Apoptosis; Isoquiritigenin; LPS/D-GalN; NLRP3 inflammasome; PGC-1α/Nrf2.

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