Astragaloside IV Attenuates Acetaminophen-Induced Liver Injuries in Mice by Activating the Nrf2 Signaling Pathway.

Lei Li,Kecheng Sun,Shoukai Wang,Yanmei Ding,Chang Liu,Wenxue Zhang,Bayaer Tumen,Wenxiang Huang,Lili Ji,Le Zhang

doi:10.3390/molecules23082032

Abstract

Acetaminophen (APAP) is a well-known antipyretic and analgesic drug. However, the accidental or intentional APAP overdose will induce liver injury and even acute liver failure. Astragaloside IV (AS-IV), a bioactive compound isolated from Astragali Radix, has been reported to have protective effects on the digestive and immune systems because of its anti-oxidant and anti-inflammatory properties. This study aims to observe whether AS-IV pretreatment provides protection against APAP-induced liver failure. The results of serum alanine/aspartate aminotransferases (ALT/AST) analysis, hepatic glutathione (GSH), and malondialdehyde (MDA) amounts, and liver superoxide dismutase (SOD) activity showed that AS-IV protected against APAP-induced hepatotoxicity. Liver histological observation further evidenced this protection provided by AS-IV. AS-IV was found to reverse the APAP-induced increased amounts of pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). Western-blot analysis showed that AS-IV increased the transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2), and enhanced the expression of heme oxygenase 1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H): quinone oxidoreductase 1 (NQO1) in the presence of APAP. AS-IV also decreased the expression of kelch-like ECH-associated protein-1 (Keap1). In conclusion, we demonstrated that AS-IV exerted a strong protection against APAP-induced hepatotoxicity by activating Nrf2 antioxidant signaling pathways.

Highlights

Liver injuries triggered by chemical medicines, known as drug-induced liver injury (DILI), is a kind of familiar and severe adverse drug reactions contributing to acute liver failure (ALF)
On the basis of statistics gained from the World Health Organization (WHO), DILI has turned out to be fifth fatal cause of death on a worldwide scale [2]
We explored the protective effects of Astragaloside IV (AS-IV) in APAP-induced liver injury

Summary

Introduction

Liver injuries triggered by chemical medicines, known as drug-induced liver injury (DILI), is a kind of familiar and severe adverse drug reactions contributing to acute liver failure (ALF). Molecules 2018, 23, 2032 other countries and regions [1]. Organization (WHO), DILI has turned out to be the fifth fatal cause of death on a worldwide scale other [2]. Countries and regions [1]. On the basis of statistics gained from the World Health Organization (WHO), DILI has turned out to be fifth fatal cause of death on a worldwide scale [2]. Acetaminophen (APAP), anthe extensively applied antipyretic and analgesic drug clinically (APAP), an extensively applied antipyretic and analgesic drug clinically worldwide, can lead to severe acute liver injury when an unexpected or intentional overdose was worldwide, can lead to severe acute liver injury when an unexpected or intentional overdose was taken [3]. Within the range of therapeutic dose, a majority of APAP catalyzed by the cytochrome taken

Objectives

Methods

Results

Conclusion