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Frontiers in cellular and infection microbiology2024; 14; 1386462; doi: 10.3389/fcimb.2024.1386462

Rutin prevents EqHV-8 induced infection and oxidative stress via Nrf2/HO-1 signaling pathway.

Abstract: The Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway has been extensively studied for its role in regulating antioxidant and antiviral responses. The Equid herpesvirus type 8 (EqHV-8) poses a significant threat to the equine industry, primarily manifesting as respiratory disease, abortions, and neurological disorders in horses and donkeys. Oxidative stress is considered a key factor associated with pathogenesis of EqHV-8 infection. Unfortunately, there is currently a dearth of therapeutic interventions available for the effective control of EqHV-8. Rutin has been well documented for its antioxidant and antiviral potential. In current study we focused on the evaluation of Rutin as a potential therapeutic agent against EqHV-8 infection. Unassigned: For this purpose, we encompassed both in-vitro and in-vivo investigations to assess the effectiveness of Rutin in combatting EqHV-8 infection. Unassigned: The results obtained from experiments demonstrated that Rutin exerted a pronounced inhibitory effect on EqHV-8 at multiple stages of the viral life cycle. Through meticulous experimentation, we elucidated that Rutin's antiviral action against EqHV-8 is intricately linked to the Nrf2/HO-1 signaling pathway-mediated antioxidant response. Activation of this pathway by Rutin was found to significantly impede EqHV-8 replication, thereby diminishing the viral load. This mechanistic insight not only enhances our understanding of the antiviral potential of Rutin but also highlights the significance of antioxidant stress responses in combating EqHV-8 infection. To complement our findings, we conducted studies employing a mouse model. These experiments revealed that Rutin administration resulted in a substantial reduction in EqHV-8 infection within the lungs of the mice, underscoring the compound's therapeutic promise . Unassigned: In summation, our finding showed that Rutin holds promise as a novel and effective therapeutic agent for the prevention and control of EqHV-8 infections.
Publication Date: 2024-04-25 PubMed ID: 38725448PubMed Central: PMC11079272DOI: 10.3389/fcimb.2024.1386462Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Summary

  • This research investigates the antiviral and antioxidant effects of Rutin against Equid herpesvirus type 8 (EqHV-8), demonstrating that Rutin inhibits the virus by activating the Nrf2/HO-1 signaling pathway, which reduces viral replication and oxidative stress.
  • Both cell culture and mouse model studies confirmed Rutin’s potential as a therapeutic agent to prevent and control EqHV-8 infection.

Background

  • EqHV-8 (Equid herpesvirus type 8): A virus causing respiratory diseases, abortions, and neurological issues in horses and donkeys, seriously impacting the equine industry.
  • Oxidative stress: A critical factor in the pathogenesis of EqHV-8 infection, where an imbalance between free radicals and antioxidants leads to cellular damage.
  • Nrf2/HO-1 signaling pathway: A molecular pathway important for regulating antioxidant defenses and antiviral responses; Nrf2 is a transcription factor that upregulates HO-1, an enzyme with protective effects against oxidative stress.
  • Rutin: A bioflavonoid known for its antioxidant and antiviral properties, proposed as a possible treatment to reduce oxidative stress and viral activity.

Research Objectives

  • To evaluate the antiviral efficacy of Rutin against EqHV-8 infection.
  • To investigate the mechanism by which Rutin influences EqHV-8 replication, particularly focusing on the Nrf2/HO-1 signaling pathway.
  • To validate the therapeutic potential of Rutin using both in vitro (cell culture) and in vivo (mouse model) systems.

Methodology

  • In vitro studies: Cell cultures infected with EqHV-8 were treated with Rutin to assess viral replication at different stages of the viral life cycle.
  • Signaling pathway analysis: Experiments were carried out to determine the involvement of the Nrf2/HO-1 pathway in the antiviral action of Rutin, examining the activation levels of Nrf2 and HO-1.
  • In vivo studies: Mice were used as an infection model where they were administered Rutin and then infected with EqHV-8, observing the impact of Rutin on lung infection severity and viral load.

Key Findings

  • Rutin exhibited significant inhibition of EqHV-8 replication in cell cultures at multiple stages, indicating broad antiviral effects.
  • Activation of the Nrf2/HO-1 pathway was closely linked to Rutin’s antiviral effects, suggesting that enhancing antioxidant defenses can suppress viral replication.
  • Rutin effectively reduced oxidative stress markers associated with EqHV-8 infection, highlighting its dual role as both an antioxidant and antiviral agent.
  • In the mouse model, Rutin treatment notably decreased viral loads in the lungs, demonstrating its in vivo therapeutic potential.

Significance and Implications

  • The study provides a molecular mechanism where Rutin activates the Nrf2/HO-1 pathway to combat viral replication and oxidative damage caused by EqHV-8.
  • It introduces Rutin as a promising candidate for developing new antiviral drugs to treat EqHV-8 infections, which currently lack effective treatments.
  • Since oxidative stress is a common factor in many viral diseases, these findings might have broader implications for antiviral therapies beyond EqHV-8.
  • The results encourage further clinical investigations and development of Rutin-based therapeutic formulations for equine viral diseases.

Conclusion

  • Rutin serves as an effective natural compound that prevents and controls EqHV-8 infection by activating the Nrf2/HO-1 antioxidant pathway, thereby reducing viral replication and oxidative stress.
  • The combination of in vitro and in vivo evidence supports the potential clinical application of Rutin as a novel antiviral agent in equine health management.

Cite This Article

APA
Chen L, Li S, Li W, Yu Y, Sun Q, Chen W, Zhou H, Wang C, Li L, Xu M, Khan MZ, Li Y, Wang T. (2024). Rutin prevents EqHV-8 induced infection and oxidative stress via Nrf2/HO-1 signaling pathway. Front Cell Infect Microbiol, 14, 1386462. https://doi.org/10.3389/fcimb.2024.1386462

Publication

ISSN: 2235-2988
NlmUniqueID: 101585359
Country: Switzerland
Language: English
Volume: 14
Pages: 1386462
PII: 1386462

Researcher Affiliations

Chen, Li
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Li, Shuwen
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Li, Wenjing
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Yu, Yue
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Sun, Qi
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Chen, Wenjing
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Zhou, Huaqi
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Wang, Changfa
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Li, Liangliang
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Xu, Meng
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Khan, Muhammad Zahoor
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Li, Yubao
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.
Wang, Tongtong
  • Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng, China.

MeSH Terms

  • Rutin / pharmacology
  • Rutin / therapeutic use
  • Animals
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects
  • Heme Oxygenase-1 / metabolism
  • Mice
  • Herpesviridae Infections / drug therapy
  • Antiviral Agents / pharmacology
  • Virus Replication / drug effects
  • Disease Models, Animal
  • Antioxidants / pharmacology
  • Cell Line
  • Viral Load / drug effects
  • Horses
  • Female
  • Membrane Proteins

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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