Improved protective effects of American ginseng berry against acetaminophen-induced liver toxicity through TNF-α-mediated caspase-3/-8/-9 signaling pathways

Abstract

Background: Similar to the leaves of P. Quinquefolius, American ginseng berry (AGB) is another important part of P. Quinquefolius with alternative therapeutic potential. The liver protection capabilities of the former have been demonstrated previously, however, the later has not yet been evaluated.

Purpose: Based on our previous observation, the present work was designed to evaluate the hepatic protective effects for novel mechanisms of AGB in acetaminophen (APAP)-induced liver injury in vivo.

Study design/methods: All mice were divided into four groups as follows: normal group, APAP group and APAP + AGB (150 mg/kg and 300 mg/kg) groups. AGB were orally administered for one week before exposure to APAP (250 mg/kg). Severe liver injury was observed and hepatotoxicity was evaluated after 24 h through evaluating the biochemical markers, protein expressions levels and liver histopathology.

Results: Our study results clearly demonstrated that AGB pretreatment ameliorated APAP-induced hepatic injury as evidenced by decreasing plasma alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) compared to the APAP group. Western blotting analysis showed that pretreatment with AGB decreased the expressions levels of TNF-α and nuclear transcription factor-κB (NF-κB p65) in liver tissues. Meanwhile, the protein expression levels of caspases, cytochrome c, and Bax were elevated by AGB treatment for seven days, while the protein expression level of Bcl-2 was inhibited comparison with that in APAP group. Furthermore, supplement of AGB resulted in increase of superoxide dismutase (SOD) and glutathione (GSH), while decrease of malondialdehyde (MDA) content and the expression levels of 4-hydroxynonenal (4-HNE) and cytochrome P450 E1 (CYP2E1). The results of histopathological staining demonstrated that AGB pretreatment inhibited APAP-induced hepatocyte infiltration, congestion, and necrosis.

Conclusion: The present study demonstrated that AGB pretreatment protected liver cells against APAP-induced hepatotoxicity through inhibition of oxidative stress, inflammation responses via TNF-α-mediated caspase-3/-8/-9 signaling pathways.

Keywords: APAP-induced liver injury; American ginseng berry; Anti-apoptosis; Anti-inflammation; Oxidative stress.