Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation

Biomed Pharmacother. 2023 Dec 31:169:115898. doi: 10.1016/j.biopha.2023.115898. Epub 2023 Nov 19.

Abstract

Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on its medicinal value, especially its potential mechanisms for alleviating ALI. This study aimed to clarify the ameliorative effects and intracellular mechanisms of VP on APAP-induced ALI via attenuating oxidative stress and inflammation. Mice were given VP for 7 days before exposure to APAP (300 mg/kg). The HPLC and radical scavenging assay found that VP contains 12 phenolic acids and 6 flavonoids, as well as show robust antioxidant capacity. In the APAP-induced ALI model, pre-treatment with VP significantly reduces APAP-induced hepatotoxicity by observing improved hepatocyte pathological injury and further confirmed by serum biochemical indicator. Also, the reduction of TUNEL-positive regions and the regulation of Bcl-2-associated X protein indicated that VP attenuates hepatocytotoxicity. Moreover, VP pre-intervention inhibits the formation of liver pro-inflammatory cytokines, the expression of inflammatory response genes, and increases in myeloperoxidase (MPO) in APAP-exposed mice. The elevated reduced glutathione (GSH) levels and decreased oxidative stress markers indicate that VP reduces APAP-promoted oxidative stress. Further study revealed that VP inhibited the phosphorylation of NF-κB/STAT3 cascade, blocked ERK and JNK phosphorylation, and activated AMP-activated protein kinase (AMPK). To sum up, this study demonstrated that VP exists hepatoprotective abilities on APAP-induced ALI, primarily by suppressing the phosphorylation of NF-κB/STAT3 cascade and ERK-JNK and inducing AMPK activation to alleviate oxidative stress and inflammation.

Keywords: AMPK; Acetaminophen (APAP); Acute liver injury (ALI); ERK-JNK; Oxidative stress; Veronica persica (VP).

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Acetaminophen / pharmacology
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Chemical and Drug Induced Liver Injury* / prevention & control
  • Inflammation / metabolism
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Veronica*

Substances

  • Acetaminophen
  • Antioxidants
  • NF-kappa B
  • AMP-Activated Protein Kinases