Quantitative Proteomic Analysis Reveals Antiviral and Anti-inflammatory Effects of Puerarin in Piglets Infected With Porcine Epidemic Diarrhea Virus

Wu, Mengjun; Zhang, Qian; Yi, Dan; Wu, Tao; Chen, Hongbo; Guo, Shuangshuang; Liu, Siyuan; Ji, Changzheng; Wang, Lei; Zhao, Di; Hou, Yongqing; Wu, Guoyao

doi:10.3389/fimmu.2020.00169

Cited by 33 publications

(37 citation statements)

References 60 publications

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“…One study has shown the upregulation of genes for IL-1β, IL-6, IL-8, and TNF-α in IPEC-J2 cells infected with PEDV 29 . Consistently, we previously reported that the mRNA levels of related inflammatory factors in Vero cells and the levels of inflammatory factors in the ileal tissue are elevated in PEDV-challenged piglets 8 . However, blood circulation is vital in the development of systemic inflammation.…”

Section: Discussionsupporting

confidence: 86%

“…Therefore, I-FABP could be used as a tissue-specific injury marker 43 , 44 . In our previous study, histologic lesions were present in the jejunum and ileum of PEDV-infected piglets, including severe villous atrophy 8 . In the present study, PEDV decreased plasma D-xylose and I-FABP concentrations, while increasing DAO activity in the plasma, indicating that PEDV induced intestinal dysfunction.…”

Section: Discussionmentioning

confidence: 80%

“…As a traditional Chinese herb, PR shows excellent antioxidant, anti-inflammatory and antimicrobial properties. Results of our previous study indicated that PR attenuated the reduction of cell proliferation in vitro, and inhibited PEDV replication and the expression of several cytokines 8 . Considering the good antioxidant property of PR and the special role of intestinal bacteria, we hypothesized that PR could alleviate PEDV-induced intestinal oxidative stress and inflammation, and modulate the intestinal flora in piglets.…”

Section: Introductionmentioning

confidence: 93%

“…In addition, PR may be used as an antimicrobial agent 6 since PR could protect porcine intestinal epithelial cells (IPEC-J2) against enterotoxigenic Escherichia coli (ETEC) infection through inhibiting bacterial adhesion and inflammatory responses 7 . The latest research found that PR could suppress the rise of mRNA levels of porcine epidemic diarrhea virus (PEDV) N and M genes in intestines of PEDV-infected piglets 8 .…”

Section: Introductionmentioning

confidence: 99%

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Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus

Zhang

et al. 2021

Sci Rep

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Puerarin has been reported to be an excellent antioxidant, anti-inflammatory and antimicrobial agent, but the potential effect of puerarin on porcine epidemic diarrhea virus (PEDV) is unclear. This study aimed to determine whether puerarin could alleviate intestinal injury in piglets infected with PEDV. A PEDV (Yunnan province strain) infection model was applied to 7-day-old piglets at 104.5 TCID50 (50% tissue culture infectious dose). Piglets were orally administered with puerarin at the dosage of 0.5 mg/kg body weight from day 5 to day 9. On day 9 of the trial, piglets were inoculated orally with PEDV. Three days later, jugular vein blood and intestinal samples were collected. Results showed puerarin reduced morbidity of piglets infected with PEDV. In addition, puerarin reduced the activities of aspartate aminotransferase and alkaline phosphatase, the ratio of serum aspartate aminotransferase to serum alanine aminotransferase, the number of white blood cells and neutrophils, and the plasma concentrations of interleukin-6, interleukin-8 and tumor necrosis factor-α, as well as protein abundances of heat shock protein-70 in PEDV-infected piglets. Moreover, puerarin increased D-xylose concentration but decreased intestinal fatty acid-binding protein concentration and diamine oxidase activity in the plasma of piglets infected with PEDV. Puerarin increased the activities of total superoxide dismutase, glutathione peroxidase and catalase, while decreasing the activities of myeloperoxidase and concentration of hydrogen peroxide in both the intestine and plasma of PEDV-infected piglets. Puerarin decreased mRNA levels of glutathione S-transferase omega 2 but increased the levels of nuclear factor erythroid 2-related factor 2. Furthermore, puerarin increased the abundance of total eubacteria (16S rRNA), Enterococcus genus, Lactobacillus genus and Enterobacteriaceae family in the intestine, but reduced the abundance of Clostridium coccoides in the caecum. These data indicate puerarin improved intestinal function in piglets infected by PEDV and may be a promising supplement for the prevention of PEDV infection.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus

Zhang

et al. 2021

Sci Rep

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“…Diarrhea is the main cause of death of newborn and suckling piglets, which brings enormous economic loss to the pig industry [1]. The occurrence of piglet diarrhea is related to genetic and improper management, especially the infection of pathogenic microorganisms, such as Escherichia coli [2], Salmonella [3], Clostridium perfringens [4][5][6], porcine epidemic diarrhea virus [7], etc. Therefore, it is necessary to search for molecular markers of diarrhea resistance and carry out porcine disease-resistant breeding.…”

Section: Introductionmentioning

confidence: 99%

ssc-miR-185 targets cell division cycle 42 and promotes the proliferation of intestinal porcine epithelial cell

Wang

Xie

et al. 2021

Anim Biosci

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Objective: microRNAs (miRNAs) can play a role in a variety of physiological and pathological regulation, and its role is achieved by regulating the expression of target genes. Our previous high-throughput sequencing found that ssc-miR-185 plays an important regulatory role in piglet diarrhea, but its specific target genes and functions in intestinal porcine epithelial cell (IPEC-J2) are still unclear. We intended to verify the target relationship between porcine miR-185 and cell division cycle 42 (CDC42) gene in IPEC-J2, and explored the effect of miR-185 on the proliferation of IPEC-J2 cells. Methods: The TargetScan, miRDB and miRanda softwares were used to predict the target genes of porcine miR-185, and CDC42 was selected as a candidate target gene. The CDC42-3'UTR-wild type (WT) and CDC42-3'UTR-mutant type (MUT) segments were successfully cloned into pmirGLO luciferase vector, and the luciferase activity was detected after co-transfection with miR-185 mimics and CDC42-3'UTR. The expression level of CDC42 was analyzed using qPCR and Western blot. The proliferation of IPEC-J2 was detected using CCK-8, MTT and EdU assays. Results: Double enzyme digestion and sequencing confirmed that CDC42-3'UTR-WT and CDC42-3'UTR-MUT were successfully cloned into pmirGLO luciferase reporter vector, and the luciferase activity was significantly reduced after co-transfection with miR-185 mimics and CDC42-3'UTR (WT). Further we found that the mRNA and protein expression level of CDC42 were down-regulated after transfection with miR-185 mimics, while the opposite trend was observed after transfection with miR-185 inhibitor (p < 0.01). In addition, the CCK-8, MTT and EdU results demonstrated that miR-185 promotes IPEC-J2 cells proliferation by targeting CDC42. Conclusion: These findings indicate that porcine miR-185 can directly target CDC42 and promote the proliferation of IPEC-J2 cells. However, the detailed regulatory mechanism of miR-185/CDC42 axis in piglets resistance to diarrhea is yet to be further investigation.

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Multifaceted Effects and Mechanisms of N‐Acetylcysteine on Intestinal Injury in a Porcine Epidemic Diarrhea Virus‐Infected Porcine Model

Zhang

Guo

et al. 2022

Molecular Nutrition Food Res

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Scope This study investigates the potential effects of N‐acetylcysteine (NAC) on intestinal injury in a porcine epidemic diarrhea virus (PEDV)‐infected porcine model. Methods and results Thirty‐two piglets are randomly assigned to one of four groups: the control, PEDV, NAC, and NAC+PEDV. Piglets in the NAC+PEDV group are orally administrated with NAC (100 mg (kg·BW)−1 day−1) for 4 consecutive days after 2 days of PEDV infection. The results show that NAC administration decreases the diarrhea rate and improves intestinal morphology. The concentration of diamine oxidase and intestinal fatty‐acid binding protein, as well as IL‐1β, IL‐8, and TNF‐α in the plasma, is decreased by NAC. Intriguingly, NAC administration significantly increases the viral load in the jejunum and ileum and down‐regulates the expression of interferon‐related genes. Microarray and proteomic analyses show that the differentially expressed genes/proteins between NAC+PEDV and PEDV groups are highly enriched in substance transport. Furthermore, aquaporin 8/10 expression is significantly increased by NAC upon PEDV infection. Conclusion NAC administration alleviates PEDV‐induced intestinal injury by inhibiting inflammatory responses and improving substance transport, but promotes viral replication by inhibiting interferon signaling. These results suggest NAC exhibits multifaceted effects upon PEDV infection, and thus caution is required when using NAC as a dietary supplement to prevent viral infection.

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Quantitative Proteomic Analysis Reveals Antiviral and Anti-inflammatory Effects of Puerarin in Piglets Infected With Porcine Epidemic Diarrhea Virus

Abstract: Collectively, these results indicate that PR could exert antiviral and anti-inflammatory effects in piglets infected with PEDV and have the potential to be an effective antiviral feed additive.

Cited by 33 publications

References 60 publications

Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus

Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus

ssc-miR-185 targets cell division cycle 42 and promotes the proliferation of intestinal porcine epithelial cell

Multifaceted Effects and Mechanisms of N‐Acetylcysteine on Intestinal Injury in a Porcine Epidemic Diarrhea Virus‐Infected Porcine Model

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