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Viruses2024; 16(11); doi: 10.3390/v16111765

Protective Role of Cepharanthine Against Equid Herpesvirus Type 8 Through AMPK and Nrf2/HO-1 Pathway Activation.

Abstract: Equid herpesvirus type 8 (EqHV-8) is known to cause respiratory disease and miscarriage in horses and donkeys, which is a major problem for the equine farming industry. However, there are currently limited vaccines or drugs available to effectively treat EqHV-8 infection. Therefore, it is crucial to develop new antiviral approaches to prevent potential pandemics caused by EqHV-8. This study evaluates the antiviral and antioxidant effects of cepharanthine against EqHV-8 by employing both in vitro assays and in vivo mouse models to assess its therapeutic efficacy. To assess the effectiveness of cepharanthine against EqHV-8, we conducted experiments using NBL-6 and RK-13 cells. Additionally, we developed a mouse model to validate cepharanthine's effectiveness against EqHV-8. In our in vitro experiments, we assessed the cepharanthine's ability to inhibit infection caused by EqHV-8 in NBL-6 and RK-13 cells. Our results demonstrated that cepharanthine has a dose-dependent inhibitory effect, indicating that it possesses anti-EqHV-8 properties at the cellular level. Moreover, we investigated the mechanism through which cepharanthine exerts its protective effects. It was observed that cepharanthine effectively reduces the oxidative stress induced by EqHV-8 by activating the AMPK and Nrf2/HO-1 signaling pathways. Furthermore, when administered to EqHV-8 infected mice, cepharanthine significantly improved lung tissue pathology and reduced oxidative stress. The findings presented herein collectively highlight cepharanthine as a promising candidate for combating EqHV-8 infections.
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Publication Date: 2024-11-12 PubMed ID: 39599879PubMed Central: PMC11598968DOI: 10.3390/v16111765Google Scholar: Lookup
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  • 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.

This study is about the discovery and validation of cepharanthine’s ability to combat Equid herpesvirus type 8 (EqHV-8), a virus causing respiratory disease and miscarriage in horses and donkeys, through activating AMPK and Nrf2/HO-1 pathways, with tests conducted in cellular (in vitro) settings and mouse models.

Understanding The Intention of The Study

  • The goal of this research was to find effective treatment means for Equid herpesvirus type 8 (EqHV-8), an equine-specific virus causing respiratory problems and miscarriage in the animal species.
  • As it was noted that there are limited drugs or vaccines available to treat this virus, there was a pressing requirement for new antiviral measures. The study explored the potential of cepharanthine, a natural compound with known strong antioxidant properties, as an antiviral agent against EqHV-8.

In Vitro and In Vivo Experiments

  • The research used two different processes to evaluate the efficacy of cepharanthine: in vitro assays, which are experimental procedures carried out in a controlled/artificial environment, like a test tube or Petri dish; and in vivo mouse models, which imply running the experiment on living organisms.
  • For the in vitro assays, two cell lines, namely NBL-6 and RK-13, were used to assess cepharanthine’s therapeutic value. Results indicated that this compound could inhibit the EqHV-8 infection in these cells.
  • A mouse model developed for this study confirmed the in vitro findings, illustrating that cepharanthine could significantly improve lung tissue pathology and reduce oxidative stress in EqHV-8 infected mice.

Unveiling The Mechanism

  • Beyond demonstrating the efficacy of cepharanthine, the research also sought to understand the pathways through which it acts.
  • Findings show that cepharanthine triggers the AMPK and Nrf2/HO-1 signaling pathways, thereby reducing the oxidative stress initiated by the EqHV-8 virus. Oxidative stress is a state of physiological stress in cells caused by an imbalance between free radicals (harmful) and antioxidants (protective) in the body.
  • The activation of these pathways by cepharanthine works to naturally restore the balance, thereby neutralizing the harmful effects of EqHV-8.

Conclusion From The Research

  • The study’s conclusive evidence indicates that cepharanthine exhibits protective effects against EqHV-8, marking it as a potential therapeutic candidate to treat this virus infection in horses and donkeys.

Cite This Article

APA
Li S, Li L, Sun Y, Khan MZ, Yu Y, Ruan L, Chen L, Zhao J, Jia J, Li Y, Wang C, Wang T. (2024). Protective Role of Cepharanthine Against Equid Herpesvirus Type 8 Through AMPK and Nrf2/HO-1 Pathway Activation. Viruses, 16(11). https://doi.org/10.3390/v16111765

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 16
Issue: 11

Researcher Affiliations

Li, Shuwen
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.
  • College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Jinzhong 030801, China.
Li, Liangliang
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.
Sun, Yijia
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.
Khan, Muhammad Zahoor
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.
Yu, Yue
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.
Ruan, Lian
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.
Chen, Li
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.
Zhao, Juan
  • College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Jinzhong 030801, China.
Jia, Junchi
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.
Li, Yubao
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.
Wang, Changfa
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.
Wang, Tongtong
  • College of Agricultural Science and Engineering, Liaocheng University, Liaocheng 252000, China.

MeSH Terms

  • Animals
  • NF-E2-Related Factor 2 / metabolism
  • Benzylisoquinolines / pharmacology
  • Benzylisoquinolines / therapeutic use
  • Mice
  • Antiviral Agents / pharmacology
  • Herpesviridae Infections / drug therapy
  • Herpesviridae Infections / virology
  • Cell Line
  • Signal Transduction / drug effects
  • Heme Oxygenase-1 / metabolism
  • AMP-Activated Protein Kinases / metabolism
  • Herpesviridae / drug effects
  • Female
  • Disease Models, Animal
  • Horses
  • Equidae
  • Benzodioxoles

Grant Funding

  • 2022YFD1600103；2023YFD1302004 / National Key R&D Program of China

Conflict of Interest Statement

The authors declare no conflicts of interest.

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Citations

This article has been cited 2 times.
  1. Khan MZ, Li Y, Zhu M, Li M, Wang T, Zhang Z, Liu W, Ma Q, Wang C. Advances in Donkey Disease Surveillance and Microbiome Characterization in China. Microorganisms 2025 Mar 26;13(4).
    doi: 10.3390/microorganisms13040749pubmed: 40284586google scholar: lookup
  2. Ruan L, Li L, Yang R, You A, Khan MZ, Yu Y, Chen L, Li Y, Liu G, Wang C, Wang T. Equine Herpesvirus-1 Induced Respiratory Disease in Dezhou Donkey Foals: Case Study from China, 2024. Vet Sci 2025 Jan 14;12(1).
    doi: 10.3390/vetsci12010056pubmed: 39852931google scholar: lookup
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