Astragalus polysaccharides inhibits PCV2 replication by inhibiting oxidative stress and blocking NF-κB pathway

Author(s):  
Hongxia Xue ◽  
Fang Gan ◽  
Zheqian Zhang ◽  
Junfa Hu ◽  
Xingxiang Chen ◽  
...  
2020 ◽  
Vol 27 (17) ◽  
pp. 20861-20875 ◽  
Author(s):  
Ashraf Awad ◽  
Samah R. Khalil ◽  
Basma M. Hendam ◽  
Reda M. Abd El-Aziz ◽  
Mohamed M. M. Metwally ◽  
...  

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2688
Author(s):  
Jingxuan Zhou ◽  
Nanhai Zhang ◽  
Liang Zhao ◽  
Wei Wu ◽  
Liebing Zhang ◽  
...  

Astragalus, a medical and edible plant in China, shows several bioactive properties. However, the role of astragalus in attenuating alcoholic liver disease (ALD) is less clear. The objective of this project is to investigate the improving effect of astragalus saponins (AS) and astragalus polysaccharides (AP), which are the two primary constituents in astragalus on hepatic injury induced by alcohol, and the potential mechanisms of action. Different doses of AS (50 and 100 mg/kg bw) and AP (300 and 600 mg/kg bw) were orally given to alcohol-treated mice for four weeks. The results demonstrated that both AP and AS could reverse the increase of the levels of TC, TG, FFA, and LDL-C in serum, and the decrease of serum HDL-C content, as well as the elevation of hepatic TC and TG levels induced by alcohol. The activities of AST, ALT, ALP, and γ-GT in ALD mice were raised after AP and AS supplementation. The antioxidant markers (SOD, CAT, GSH, and GSH-Px) were obviously augmented and the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and hepatic histological variations were alleviated by AP and AS, which was in line with the levels of oxidative stress-associated genes (Keap1, Nfe2l2, Nqo1, and Hmox1) and inflammation-associated genes (Tlr4, Myd88 and Nfkb1). In addition, AS exerted a more efficient effect than AP and the results presented dose proportionality. Moreover, AS and AP could modulate the intestinal microbiota disturbance induced by alcohol. Overall, AS and AP administration could ameliorate lipid accumulation in the serum and liver, as well as hepatic function, oxidative stress, inflammatory response, and gut flora disorders in mice as a result of alcohol.


Oncotarget ◽  
2016 ◽  
Vol 7 (15) ◽  
pp. 20469-20485 ◽  
Author(s):  
Fang Gan ◽  
Zhihua Hu ◽  
Yu Huang ◽  
Hongxia Xue ◽  
Da Huang ◽  
...  

2021 ◽  
Author(s):  
Renjie Sun ◽  
Zhuofan Deng ◽  
Xiao Han ◽  
Yikai Zhang ◽  
Yingshan Zhou ◽  
...  

Porcine circovirus type 2 (PCV2) causes several disease syndromes in grower pigs. PCV2 infection triggers endoplasmic reticulum (ER) stress, autophagy and oxidative stress, all of which support PCV2 replication. We have recently reported that nuclear HMGB1 is an anti-PCV2 factor by binding to viral genomic DNA. However, how PCV2 manipulates host cell responses to favor its replication has not been explored. Here, we demonstrate that PCV2 infection increased expression of ERO1α, generation of ROS and nucleocytoplasmic migration of HMGB1 via PERK activation in PK-15 cells. Inhibition of PERK or ERO1α repressed ROS production in PCV2-infected cells and increased HMGB1 retention within nuclei. These findings indicate that PCV2-induced activation of the PERK-ERO1α axis would lead to enhanced generation of ROS sufficient to decrease HMGB1 retention in the nuclei, thus derepressing viral DNA from HMGB1 sequestration. The viral Rep and Cap proteins were able to induce PERK-ERO1α-mediated ROS accumulation. Cysteine residues 107 and 305 of Rep or 108 of Cap played important roles in PCV2-induced PERK activation and distribution of HMGB1. Of the mutant viruses, only the mutant PCV2 with substitution of all three cysteine residues failed to activate PERK with reduced ROS generation and decreased nucleocytoplasmic migration of HMGB1. Collectively, this study offers novel insight into the mechanism of enhanced viral replication in which PCV2 manipulates ER to perturb its redox homeostasis via the PERK-ERO1α axis and the ER-sourced ROS from oxidative folding is sufficient to reduce HMGB1 retention in the nuclei, hence the release of HMGB1-bound viral DNA for replication. IMPORTANCE Considering the fact that clinical PCVAD mostly results from activation of latent PCV2 infection by confounding factors such as co-infection or environmental stresses, we propose that such confounding factors might impose oxidative stress to the animals where PCV2 in infected cells might utilize the elevated ROS to promote HMGB1 migration out of nuclei in favor of its replication. An animal infection model with a particular stressor could be approached with or without antioxidant treatment to examine the relationship among the stressor, ROS level, HMGB1 distribution in target tissues, virus replication and severity of PCVAD. This will help decide the use of antioxidants in the feeding regime on pig farms that suffer from PCVAD. Further investigation could examine if similar strategies are employed by DNA viruses, such as PCV3 and BFDV and if there is cross-talk among ER stress, autophagy/mitophagy and mitochondria-sourced ROS in favor of PCV2 replication.


2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Nianhui Zhai ◽  
Kai Liu ◽  
Hu Li ◽  
Zixuan Liu ◽  
Hong Wang ◽  
...  

2020 ◽  
Vol 11 (10) ◽  
pp. 8547-8559
Author(s):  
Hongjing Zhao ◽  
Yu Wang ◽  
Mengyao Mu ◽  
Menghao Guo ◽  
Hongxian Yu ◽  
...  

Antibiotics are used worldwide to treat diseases in humans and other animals; most of them and their secondary metabolites are discharged into the aquatic environment, posing a serious threat to human health.


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