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  2. Sappanone A ameliorates acetaminophen-induced acute liver injury in mice

Sappanone A ameliorates acetaminophen-induced acute liver injury in mice

  • Toxicology. 2022 Oct;480:153336. doi: 10.1016/j.tox.2022.153336.
Zixiong Zhou 1 Yong Wu 2 Wenxi Hua 2 Xueqing Yan 3 Lanqian Li 2 An Zhu 4 Jing Qi 5
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, Fujian, China; Department of Pathology and Institute of Oncology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, Fujian, China; Diagnostic Pathology Center, Fujian Medical University, Fuzhou 350122, Fujian, China.
  • 2 Department of Pathology and Institute of Oncology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, Fujian, China; Diagnostic Pathology Center, Fujian Medical University, Fuzhou 350122, Fujian, China.
  • 3 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, Fujian, China.
  • 4 Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, Fujian, China. Electronic address: [email protected].
  • 5 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, Fujian, China. Electronic address: [email protected].
Abstract

Sappanone A (SA), a homoisoflavonoid compound extracted from the heartwood of Caesalpinia sappan Linn., exerts anti-inflammatory and antioxidant activities. However, the effects of SA on acetaminophen (APAP) overdose-induced acute liver injury (ALI) have not been determined yet. This study aims to explore the protective effects of SA and the potential mechanisms of action. Mice were pretreated with SA (25, 50, and 100 mg/kg) by intraperitoneal (i.p.) injection for seven days prior to APAP (300 mg/kg, i.p.) administration. At 12 h after APAP injection, serum and liver samples were collected. Primary murine hepatocytes were used to investigate the underlying mechanisms. SA pretreatment dose-dependently attenuated APAP-induced ALI, as validated by reduced serum alanine/aspartate aminotransferase levels, histopathologic lesions, and oxidative stress. Consistently, pretreatment with SA reduced the formation of APAP protein adducts in damaged livers of mice. Mechanistically, SA could facilitate the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and thus promote cellular glutathione (GSH) synthesis. The hepatoprotective outcomes provided by SA were significantly abolished by treatment with ML385, a Nrf2 inhibitor. Besides, anti-inflammatory property of SA reduced inflammatory reaction in injured livers of mice. Of note, posttreatment with SA reveals significant therapeutic influences against APAP-induced ALI in mice. Collectively, our findings demonstrated that pretreated-SA ameliorated APAP-mediated ALI in mice, at least in part, by reducing the generation of APAP protein adducts via Nrf2-enhanced GSH synthesis, and by diminishing hepatic inflammation. Therefore, SA could be a potential hepatoprotective agent for treating ALI.

Keywords

APAP overdose-induced ALI; GSH; Inflammation; Nrf2; Sappanone A.

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