Astragaloside IV Attenuates Acetaminophen-Induced Liver Injuries in Mice by Activating the Nrf2 Signaling Pathway
Lei Li,
Wenxiang Huang,
Shoukai Wang,
Kecheng Sun,
Wenxue Zhang,
Yanmei Ding,
Le Zhang,
Bayaer Tumen,
Lili Ji,
Chang Liu
Affiliations
Lei Li
The Shanghai Key Laboratory of Compound Chinese Medicines and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Wenxiang Huang
Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China
Shoukai Wang
Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China
Kecheng Sun
Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China
Wenxue Zhang
Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China
Yanmei Ding
Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China
Le Zhang
Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China
Bayaer Tumen
Veterinary Laboratory, Shanxi Animal Disease Control Center, Taiyuan 030027, China
Lili Ji
The Shanghai Key Laboratory of Compound Chinese Medicines and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Chang Liu
Key Laboratory of Quality & Safety Control for Pork, Ministry of Agriculture and Rural, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China
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.
