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

• Published in: Biomedicine & pharmacotherapy 2023-12, Vol.169, p.115898-115898, Article 115898
• Main Authors: Tian, Wei-shun, Zhao, Jing, Kim, Myung-Kon, Tae, Hyun-Jin, Kim, In-Shik, Ahn, Dongchoon, Hwang, Hong Pil, Mao, Ming-xian, Park, Byung-Yong
• Format: Article
• Language: English
• Subjects: Acetaminophen (APAP); Acute liver injury (ALI); AMPK; ERK-JNK; Oxidative stress; Veronica persica (VP)
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.115898

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. [Display omitted] •VP ameliorates APAP-induced hepatotoxicity.•VP increases GSH production, and attenuates CYP2E1 mRNA expression.•VP inhibits pro-inflammatory cytokines and neutrophil infiltration.•VP mitigates ALI via attenuating ERK-JNK/NF-κB/STAT3 and activating AMPK phosphorylation.