FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of virology2024; 98(4); e0015924; doi: 10.1128/jvi.00159-24

Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways.

Abstract: Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin-Darby bovine kidney), and NBL-6 cells (E. Derm cells). Mechanistic investigations revealed that hyperoside induces heme oxygenase-1 expression by activating the c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis, alleviating oxidative stress and triggering a downstream antiviral interferon response. Accordingly, hyperoside inhibits EHV-8 infection. Meanwhile, hyperoside can also mitigate EHV-8-induced injury in the lungs of infected mice. These results indicate that hyperoside may serve as a novel antiviral agent against EHV-8 infection.IMPORTANCEHyperoside has been reported to suppress viral infections, including herpesvirus, hepatitis B virus, infectious bronchitis virus, and severe acute respiratory syndrome coronavirus 2 infection. However, its mechanism of action against equine herpesvirus type 8 (EHV-8) is currently unknown. Here, we demonstrated that hyperoside significantly inhibits EHV-8 adsorption and internalization in susceptible cells. This process induces HO-1 expression via c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis activation, alleviating oxidative stress and triggering an antiviral interferon response. These findings indicate that hyperoside could be very effective as a drug against EHV-8.
Get Full Text
Publication Date: 2024-03-19 PubMed ID: 38499512PubMed Central: PMC11019850DOI: 10.1128/jvi.00159-24Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • 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.

Overview

  • This study investigates the antiviral effects of hyperoside against equine herpesvirus type 8 (EHV-8) infection and elucidates the molecular mechanisms involved in its protective action.

Background and Significance

  • EHV-8 is a virus that causes abortion and respiratory disease in horses and donkeys, leading to significant economic losses worldwide.
  • Currently, there are no effective vaccines or treatments available to prevent or control EHV-8 infection.
  • This gap in treatment options highlights the need to identify novel antiviral agents to lower EHV-8’s impact on equine health and the industry.

Research Objectives

  • To evaluate whether hyperoside, a natural compound previously shown to inhibit other viral infections, can suppress EHV-8 infection.
  • To clarify the underlying molecular mechanisms by which hyperoside exerts its antiviral effects.
  • To determine if hyperoside can reduce tissue damage caused by EHV-8 infection in vivo.

Methodology

  • Cell Culture Models: The antiviral effects of hyperoside were tested in three cell lines susceptible to EHV-8 infection — RK-13 (rabbit kidney cells), MDBK (bovine kidney cells), and NBL-6 (E. Derm equine cells).
  • Viral Infection Assays: The study measured hyperoside’s ability to inhibit viral adsorption (attachment to host cells) and internalization (entry into cells).
  • Signaling Pathway Analysis: Investigations focused on the activation of the JNK (c-Jun N-terminal kinase)/Keap1/Nrf2 (nuclear factor erythroid-2-related factor 2)/HO-1 (heme oxygenase-1) signaling axis.
  • Oxidative Stress and Immune Response: The effect of hyperoside on oxidative stress reduction and induction of antiviral interferon production was assessed.
  • In Vivo Experimentation: Lung tissue from EHV-8 infected mice treated with hyperoside was examined to observe protective effects against viral injury.

Key Findings

  • Hyperoside effectively inhibited EHV-8 infection across all tested cell types by significantly reducing viral adsorption and entry.
  • Mechanistically, hyperoside activated the JNK/Keap1/Nrf2/HO-1 pathway, which led to increased expression of HO-1, a protein known for its antioxidant and cytoprotective properties.
  • Activation of this pathway reduced oxidative stress in infected cells, which is critical because viral infections often induce harmful oxidative damage.
  • Reduced oxidative stress subsequently enhanced the production of antiviral interferons, key components of the innate immune response against viruses.
  • In mouse models, hyperoside treatment minimized lung injury caused by EHV-8 infection, indicating its potential for protecting tissue from virus-induced damage in living organisms.

Mechanistic Insights

  • The JNK (c-Jun N-terminal kinase) pathway is a stress-activated protein kinase pathway that can regulate cellular responses to stress, including viral infections.
  • Keap1 serves as a negative regulator of Nrf2, which controls the expression of antioxidant proteins like HO-1.
  • When JNK is activated, it promotes Nrf2 to dissociate from Keap1 and translocate to the nucleus, where it upregulates HO-1 expression.
  • HO-1 has antioxidative and anti-inflammatory roles; its induction helps to reduce oxidative cellular damage during viral infection.
  • By alleviating oxidative stress, hyperoside indirectly supports the host’s antiviral defense by promoting interferon production, which inhibits viral replication.

Implications and Potential Applications

  • The identification of hyperoside as a potent inhibitor of EHV-8 offers a promising lead compound for developing antiviral therapies in equine veterinary medicine.
  • By targeting host cellular pathways to boost antiviral defenses rather than solely attacking the virus, hyperoside may reduce the risk of viral resistance development.
  • Given hyperoside’s broad antiviral activity against other viruses, this study supports further exploration of its clinical applications for multiple viral infections.
  • Future research could involve clinical trials in equines, dosage optimization, and assessment of hyperoside’s safety profile in animals.

Cite This Article

APA
Wang T, Hu L, Li R, Ren H, Li S, Sun Q, Ding X, Li Y, Wang C, Li L. (2024). Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways. J Virol, 98(4), e0015924. https://doi.org/10.1128/jvi.00159-24

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 98
Issue: 4
Pages: e0015924
PII: e00159-24

Researcher Affiliations

Wang, Tongtong
  • College of Agronomy, Liaocheng University, Liaocheng, China.
Hu, Leyu
  • College of Agronomy, Liaocheng University, Liaocheng, China.
  • College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, China.
Li, Ruibo
  • College of Agronomy, Liaocheng University, Liaocheng, China.
Ren, Huiying
  • College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, China.
Li, Shuwen
  • College of Agronomy, Liaocheng University, Liaocheng, China.
Sun, Qi
  • College of Agronomy, Liaocheng University, Liaocheng, China.
Ding, Xiangdan
  • College of Agronomy, Liaocheng University, Liaocheng, China.
Li, Yubao
  • College of Agronomy, Liaocheng University, Liaocheng, China.
Wang, Changfa
  • College of Agronomy, Liaocheng University, Liaocheng, China.
Li, Liangliang
  • College of Agronomy, Liaocheng University, Liaocheng, China.

MeSH Terms

  • Animals
  • Cattle
  • Mice
  • Rabbits
  • Antiviral Agents / pharmacology
  • Herpesviridae Infections
  • Herpesvirus 1, Equid
  • Horses
  • Interferons / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • MAP Kinase Signaling System
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Quercetin / analogs & derivatives
  • Quercetin / pharmacology
  • Cell Line

Grant Funding

  • 32002248 / MOST | National Natural Science Foundation of China (NSFC)
  • ZR2020QC016 / | Natural Science Foundation of Shandong Province ()
  • ZR2020QC017 / | Natural Science Foundation of Shandong Province ()

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 53 references
  1. Wang T, Hu L, Liu M, Wang T, Hu X, Li Y, Liu W, Li Y, Wang Y, Ren H, Zhang W, Wang C, Li L. The emergence of viral encephalitis in donkeys by equid herpesvirus 8 in China. Front Microbiol 13:840754.
    doi: 10.3389/fmicb.2022.840754pmc: PMC8930201pubmed: 35308333google scholar: lookup
  2. Wang T, Xi C, Yu Y, Liu W, Akhtar MF, Li Y, Wang C, Li L. Characteristics and epidemiological investigation of equid herpesvirus 8 in donkeys in Shandong, China. Arch Virol 168:99.
    doi: 10.1007/s00705-023-05704-xpubmed: 36871102google scholar: lookup
  3. Liu C, Guo W, Lu G, Xiang W, Wang X. Complete genomic sequence of an equine herpesvirus type 8 Wh strain isolated from China. J Virol 86:5407.
    doi: 10.1128/JVI.00445-12pmc: PMC3347380pubmed: 22492929google scholar: lookup
  4. Wang T, Hu L, Wang Y, Liu W, Liu G, Zhu M, Zhang W, Wang C, Ren H, Li L. Identification of equine herpesvirus 8 in donkey abortion: a case report. Virol J 19:10.
    doi: 10.1186/s12985-021-01738-2pmc: PMC8734136pubmed: 34991640google scholar: lookup
  5. Zhong M, Wang H, Ma L, Yan H, Wu S, Gu Z, Li Y. DMO-CAP inhibits influenza virus replication by activating heme oxygenase-1-mediated IFN response. Virol J 16:21.
    doi: 10.1186/s12985-019-1125-9pmc: PMC6381609pubmed: 30786886google scholar: lookup
  6. Lu W, Shi L, Gao J, Zhu H, Hua Y, Cai J, Wu X, Wan C, Zhao W, Zhang B. Piperlongumine inhibits Zika virus replication in vitro and promotes up-regulation of HO-1 expression, suggesting an implication of oxidative stress. Virol Sin 36:510–520.
    doi: 10.1007/s12250-020-00310-6pmc: PMC8257849pubmed: 33185862google scholar: lookup
  7. Feng Y, Guo X, Tian H, He Y, Li Y, Jiang X, Zheng H, Xiao S. Induction of HOXA3 by porcine reproductive and respiratory syndrome virus inhibits type I interferon response through negative regulation of HO-1 transcription. J Virol 96:e0186321.
    doi: 10.1128/JVI.01863-21pmc: PMC8827019pubmed: 34851144google scholar: lookup
  8. Ye P, Yang XL, Chen X, Shi C. Hyperoside attenuates OVA-induced allergic airway inflammation by activating Nrf2. Int Immunopharmacol 44:168–173.
    doi: 10.1016/j.intimp.2017.01.003pubmed: 28107754google scholar: lookup
  9. Ku SK, Zhou W, Lee W, Han MS, Na M, Bae JS. Anti-inflammatory effects of hyperoside in human endothelial cells and in mice. Inflammation 38:784–799.
    doi: 10.1007/s10753-014-9989-8pubmed: 25097077google scholar: lookup
  10. Qiu J, Zhang T, Zhu X, Yang C, Wang Y, Zhou N, Ju B, Zhou T, Deng G, Qiu C. Hyperoside induces breast cancer cells apoptosis via ROS-mediated NF-kappaB signaling pathway. Int J Mol Sci 21:131.
    doi: 10.3390/ijms21010131pmc: PMC6981893pubmed: 31878204google scholar: lookup
  11. Fan H, Li Y, Sun M, Xiao W, Song L, Wang Q, Zhang B, Yu J, Jin X, Ma C, Chai Z. Hyperoside reduces rotenone-induced neuronal injury by suppressing autophagy. Neurochem Res 46:3149–3158.
    doi: 10.1007/s11064-021-03404-zpubmed: 34415495google scholar: lookup
  12. Park JY, Han X, Piao MJ, Oh MC, Fernando P, Kang KA, Ryu YS, Jung U, Kim IG, Hyun JW. Hyperoside induces endogenous antioxidant system to alleviate oxidative stress. J Cancer Prev 21:41–47.
    doi: 10.15430/JCP.2016.21.1.41pmc: PMC4819665pubmed: 27051648google scholar: lookup
  13. Chen H, Muhammad I, Zhang Y, Ren Y, Zhang R, Huang X, Diao L, Liu H, Li X, Sun X, Abbas G, Li G. Antiviral activity against infectious bronchitis virus and bioactive components of Hypericum perforatum L.. Front Pharmacol 10:1272.
    doi: 10.3389/fphar.2019.01272pmc: PMC6830131pubmed: 31736754google scholar: lookup
  14. Li J, Huang H, Zhou W, Feng M, Zhou P. Anti-hepatitis B virus activities of Geranium carolinianum L. extracts and identification of the active components. Biol Pharm Bull 31:743–747.
    doi: 10.1248/bpb.31.743pubmed: 18379075google scholar: lookup
  15. Fritz D, Venturi CR, Cargnin S, Schripsema J, Roehe PM, Montanha JA, von Poser GL. Herpes virus inhibitory substances from Hypericum connatum Lam., a plant used in southern Brazil to treat oral lesions. J Ethnopharmacol 113:517–520.
    doi: 10.1016/j.jep.2007.07.013pubmed: 17719731google scholar: lookup
  16. Wu LL, Yang XB, Huang ZM, Liu HZ, Wu GX. In vivo and in vitro antiviral activity of hyperoside extracted from Abelmoschus manihot (L) medik.. Acta Pharmacol Sin 28:404–409.
    doi: 10.1111/j.1745-7254.2007.00510.xpubmed: 17303004google scholar: lookup
  17. Zhao J, Tian S, Lu D, Yang J, Zeng H, Zhang F, Tu D, Ge G, Zheng Y, Shi T, Xu X, Zhao S, Yang Y, Zhang W. Systems pharmacological study illustrates the immune regulation, anti-infection, anti-inflammation, and multi-organ protection mechanism of Qing-Fei-Pai-Du decoction in the treatment of COVID-19.. Phytomedicine 85:153315.
    doi: 10.1016/j.phymed.2020.153315pmc: PMC7480398pubmed: 32978039google scholar: lookup
  18. Kwon S-H, Lee SR, Park YJ, Ra M, Lee Y, Pang C, Kim KH. Suppression of 6-hydroxydopamine-induced oxidative stress by hyperoside via activation of Nrf2/HO-1 signaling in dopaminergic neurons.. Int J Mol Sci 20:5832.
    doi: 10.3390/ijms20235832pmc: PMC6929192pubmed: 31757050google scholar: lookup
  19. Chen Y, Ye L, Li W, Li D, Li F. Hyperoside protects human kidney2 cells against oxidative damage induced by oxalic acid.. Mol Med Rep 18:486–494.
    doi: 10.3892/mmr.2018.8948pubmed: 29750296google scholar: lookup
  20. Waza AA, Hamid Z, Ali S, Bhat SA, Bhat MA. A review on heme oxygenase-1 induction: is it a necessary evil.. Inflamm Res 67:579–588.
    doi: 10.1007/s00011-018-1151-xpubmed: 29693710google scholar: lookup
  21. Facchinetti MM. Heme-oxygenase-1.. Antioxid Redox Signal 32:1239–1242.
    doi: 10.1089/ars.2020.8065pubmed: 32148070google scholar: lookup
  22. Ma LL, Zhang P, Wang HQ, Li YF, Hu J, Jiang JD, Li YH. heme oxygenase-1 agonist CoPP suppresses influenza virus replication through IRF3-mediated generation of IFN-alpha/beta.. Virology 528:80–88.
    doi: 10.1016/j.virol.2018.11.016pubmed: 30580124google scholar: lookup
  23. Diamond MS, Farzan M. The broad-spectrum antiviral functions of IFIT and IFITM proteins.. Nat Rev Immunol 13:46–57.
    doi: 10.1038/nri3344pmc: PMC3773942pubmed: 23237964google scholar: lookup
  24. Stępkowski TM, Kruszewski MK. Molecular cross-talk between the NRF2/KEAP1 signaling pathway, autophagy, and apoptosis.. Free Radic Biol Med 50:1186–1195.
    doi: 10.1016/j.freeradbiomed.2011.01.033pubmed: 21295136google scholar: lookup
  25. Bellezza I, Giambanco I, Minelli A, Donato R. Nrf2-Keap1 signaling in oxidative and reductive stress.. Biochim Biophys Acta Mol Cell Res 1865:721–733.
    doi: 10.1016/j.bbamcr.2018.02.010pubmed: 29499228google scholar: lookup
  26. He F, Ru X, Wen T. NRF2, a transcription factor for stress response and beyond.. Int J Mol Sci 21:4777.
    doi: 10.3390/ijms21134777pmc: PMC7369905pubmed: 32640524google scholar: lookup
  27. Hu L, Wang T, Ren H, Liu W, Li Y, Wang C, Li L. Characterizing the pathogenesis and immune response of equine herpesvirus 8 infection in lung of mice.. Animals (Basel) 12:2495.
    doi: 10.3390/ani12192495pmc: PMC9559255pubmed: 36230234google scholar: lookup
  28. Elrasoul ASA, Mousa AA, Orabi SH, Mohamed M-G, Gad-Allah SM, Almeer R, Abdel-Daim MM, Khalifa SAM, El-Seedi HR, Eldaim MAA. Antioxidant, anti-inflammatory, and anti-apoptotic effects of Azolla pinnata ethanolic extract against lead-induced hepatotoxicity in rats.. Antioxidants (Basel) 9:1014.
    doi: 10.3390/antiox9101014pmc: PMC7603163pubmed: 33086604google scholar: lookup
  29. Jin XN, Yan EZ, Wang HM, Sui HJ, Liu Z, Gao W, Jin Y. Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated human fibroblast-like synoviocytes in vitro and in mice with collagen-induced arthritis.. Acta Pharmacol Sin 37:674–686.
    doi: 10.1038/aps.2016.7pmc: PMC4857551pubmed: 27041460google scholar: lookup
  30. Li FR, Yu FX, Yao ST, Si YH, Zhang W, Gao LL. Hyperin extracted from Manchurian rhododendron leaf induces apoptosis in human endometrial cancer cells through a mitochondrial pathway.. Asian Pac J Cancer Prev 13:3653–3656.
    doi: 10.7314/apjcp.2012.13.8.3653pubmed: 23098449google scholar: lookup
  31. Yeh Y-C, Doan LH, Huang Z-Y, Chu L-W, Shi T-H, Lee Y-R, Wu C-T, Lin C-H, Chiang S-T, Liu H-K, Chuang T-H, Ping Y-H, Liu H-S, Huang C-Y. Honeysuckle (Lonicera japonica) and huangqi (Astragalus membranaceus) suppress SARS-CoV-2 entry and COVID-19 related cytokine storm in vitro. Front Pharmacol 12.
    doi: 10.3389/fphar.2021.765553pmc: PMC8990830pubmed: 35401158google scholar: lookup
  32. Avula K, Singh B, Kumar PV, Syed GH. Role of lipid transfer proteins (LTPs) in the viral life cycle. Front Microbiol 12:673509.
    doi: 10.3389/fmicb.2021.673509pmc: PMC8260984pubmed: 34248884google scholar: lookup
  33. Oladunni FS, Horohov DW, Chambers TM. EHV-1: a constant threat to the horse industry. Front Microbiol 10:2668.
    doi: 10.3389/fmicb.2019.02668pmc: PMC6901505pubmed: 31849857google scholar: lookup
  34. Sutter J, Bruggeman PJ, Wigdahl B, Krebs FC, Miller V. Manipulation of oxidative stress responses by non-thermal plasma to treat herpes simplex virus type 1 infection and disease. Int J Mol Sci 24:4673.
    doi: 10.3390/ijms24054673pmc: PMC10003306pubmed: 36902102google scholar: lookup
  35. Liu X, Song Z, Bai J, Nauwynck H, Zhao Y, Jiang P. Xanthohumol inhibits PRRSV proliferation and alleviates oxidative stress induced by PRRSV via the Nrf2-HMOX1 axis. Vet Res 50:61.
    doi: 10.1186/s13567-019-0679-2pmc: PMC6737628pubmed: 31506103google scholar: lookup
  36. Mifsud EJ, Kuba M, Barr IG. Innate immune responses to influenza virus infections in the upper respiratory tract. Viruses 13:2090.
    doi: 10.3390/v13102090pmc: PMC8541359pubmed: 34696520google scholar: lookup
  37. Mesev EV, LeDesma RA, Ploss A. Decoding type I and III interferon signalling during viral infection. Nat Microbiol 4:914–924.
    doi: 10.1038/s41564-019-0421-xpmc: PMC6554024pubmed: 30936491google scholar: lookup
  38. Oladunni FS, Sarkar S, Reedy S, Balasuriya UBR, Horohov DW, Chambers TM. Equid herpesvirus 1 targets the sensitization and induction steps to inhibit the type I interferon response in equine endothelial cells. J Virol 93:e01342-19.
    doi: 10.1128/JVI.01342-19pmc: PMC6854505pubmed: 31511388google scholar: lookup
  39. Espinoza JA, León MA, Céspedes PF, Gómez RS, Canedo-Marroquín G, Riquelme SA, Salazar-Echegarai FJ, Blancou P, Simon T, Anegon I, Lay MK, González PA, Riedel CA, Bueno SM, Kalergis AM. Heme oxygenase-1 modulates human respiratory syncytial virus replication and lung pathogenesis during infection. J Immunol 199:212–223.
    doi: 10.4049/jimmunol.1601414pubmed: 28566367google scholar: lookup
  40. Behl T, Rana T, Alotaibi GH, Shamsuzzaman M, Naqvi M, Sehgal A, Singh S, Sharma N, Almoshari Y, Abdellatif AAH, Iqbal MS, Bhatia S, Al-Harrasi A, Bungau S. Polyphenols inhibiting MAPK signalling pathway mediated oxidative stress and inflammation in depression. Biomed Pharmacother 146:112545.
    doi: 10.1016/j.biopha.2021.112545pubmed: 34922112google scholar: lookup
  41. Chander Y, Kumar R, Khandelwal N, Singh N, Shringi BN, Barua S, Kumar N. Role of p38 mitogen-activated protein kinase signalling in virus replication and potential for developing broad spectrum antiviral drugs. Rev Med Virol 31:1–16.
    doi: 10.1002/rmv.2217pubmed: 33450133google scholar: lookup
  42. Seminotti B, Grings M, Tucci P, Leipnitz G, Saso L. Nuclear factor erythroid-2-related factor 2 signaling in the neuropathophysiology of inherited metabolic disorders. Front Cell Neurosci 15:785057.
    doi: 10.3389/fncel.2021.785057pmc: PMC8693715pubmed: 34955754google scholar: lookup
  43. Zhang Y, Shi Z, Zhou Y, Xiao Q, Wang H, Peng Y. Emerging substrate proteins of kelch-like ECH associated protein 1 (Keap1) and potential challenges for the development of small-molecule inhibitors of the Keap1-nuclear factor erythroid 2-related factor 2 (Nrf2) protein-protein interaction. J Med Chem 63:7986–8002.
    doi: 10.1021/acs.jmedchem.9b01865pubmed: 32233486google scholar: lookup
  44. Kesic MJ, Simmons SO, Bauer R, Jaspers I. Nrf2 expression modifies influenza A entry and replication in nasal epithelial cells. Free Radic Biol Med 51:444–453.
    doi: 10.1016/j.freeradbiomed.2011.04.027pmc: PMC3135631pubmed: 21549835google scholar: lookup
  45. Nitti M, Ivaldo C, Traverso N, Furfaro AL. Clinical significance of heme oxygenase 1 in tumor progression. Antioxidants (Basel) 10:789.
    doi: 10.3390/antiox10050789pmc: PMC8155918pubmed: 34067625google scholar: lookup
  46. Kovacsics CE, Gill AJ, Ambegaokar SS, Gelman BB, Kolson DL. Degradation of heme oxygenase-1 by the immunoproteasome in astrocytes: a potential interferon-gamma-dependent mechanism contributing to HIV neuropathogenesis.. Glia 65:1264–1277.
    doi: 10.1002/glia.23160pmc: PMC5739592pubmed: 28543773google scholar: lookup
  47. Zhang Q, Liu J, Duan H, Li R, Peng W, Wu C. Activation of Nrf2/HO-1 signaling: an important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress.. J Adv Res 34:43–63.
    doi: 10.1016/j.jare.2021.06.023pmc: PMC8655139pubmed: 35024180google scholar: lookup
  48. Tseng CK, Hsu SP, Lin CK, Wu YH, Lee JC, Young KC. Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells.. Antiviral Res 146:191–200.
    doi: 10.1016/j.antiviral.2017.09.010pmc: PMC7113881pubmed: 28935193google scholar: lookup
  49. Xing HY, Liu Y, Chen JH, Sun FJ, Shi HQ, Xia PY. Hyperoside attenuates hydrogen peroxide-induced L02 cell damage via MAPK-dependent Keap(1)-Nrf(2)-ARE signaling pathway.. Biochem Biophys Res Commun 410:759–765.
    doi: 10.1016/j.bbrc.2011.06.046pubmed: 21689633google scholar: lookup
  50. Li L, Sun W, Hu Q, Wang T, Zhu G, Zhao Q, Zhou EM. Identification of MYH9 key domain involved in the entry of PRRSV into permissive cells.. Front Microbiol 13:865343.
    doi: 10.3389/fmicb.2022.865343pmc: PMC9174932pubmed: 35694306google scholar: lookup
  51. Li L, Zhang L, Hu Q, Zhao L, Nan Y, Hou G, Chen Y, Han X, Ren X, Zhao Q, Tao H, Sun Z, Zhang G, Wu C, Wang J, Zhou EM. MYH9 key amino acid residues identified by the anti-idiotypic antibody to porcine reproductive and respiratory syndrome virus glycoprotein 5 involve in the virus internalization by porcine alveolar macrophages.. Viruses 12:40.
    doi: 10.3390/v12010040pmc: PMC7019770pubmed: 31905776google scholar: lookup
  52. Wang T, Du Q, Niu Y, Zhang X, Wang Z, Wu X, Yang X, Zhao X, Liu SL, Tong D, Huang Y. Cellular p32 is a critical regulator of porcine circovirus type 2 nuclear egress.. J Virol 93:e00979-19.
    doi: 10.1128/JVI.00979-19pmc: PMC6854514pubmed: 31511386google scholar: lookup
  53. Mesquita LP, Costa RC, Mesquita LLR, Lara M do C, Villalobos EMC, Mori CMC, Mori E, Howerth EW, Maiorka PC. Pathogenesis of equid alphaherpesvirus 1 infection in the central nervous system of mice.. Vet Pathol 58:1075–1085.
    doi: 10.1177/03009858211020670pubmed: 34128432google scholar: lookup

Citations

This article has been cited 8 times.
  1. Xue C, Ge H, Liu Y, Zhao Y, Huang W, Lu Z, Ye Q, Chen X, Cao Z. Therapeutic potential of Abelmoschus manihot: mechanisms of action and clinical use in traditional Chinese medicine formulas. Front Pharmacol 2025;16:1709530.
    doi: 10.3389/fphar.2025.1709530pubmed: 41451365google scholar: lookup
  2. Ullah A, Khan MZ, Wang C. Overview of Donkey Welfare and Husbandry Practices in Asia. Animals (Basel) 2025 Dec 1;15(23).
    doi: 10.3390/ani15233464pubmed: 41375522google scholar: lookup
  3. Wang T, Chen L, Wang A, Xu Y, Zhang Y, Zhao Q, Ren Q, Liu S, Li L, Li Y, Wu J. Hyperoside inhibits PRRSV proliferation via the TLR4/NF-κB and p62-Nrf2-Keap1 signaling pathways, mediating inflammation and autophagy. Microbiol Spectr 2025 Aug 5;13(8):e0310724.
    doi: 10.1128/spectrum.03107-24pubmed: 40503831google scholar: lookup
  4. 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
  5. Yu Y, Wang J, Ruan L, Chen L, Khan MZ, You A, Wang C, Li L, Ren H, Wang T, Liu W. Evaluation of Celastrol Antiviral Activity Against Equid Alphaherpesvirus Type 8 Infection. Viruses 2025 Feb 28;17(3).
    doi: 10.3390/v17030347pubmed: 40143276google scholar: lookup
  6. 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
  7. Li X, Zhou W, Chen J, Zhou L, Li Y, Wu X, Peng X. Circ_001653 alleviates sepsis associated-acute kidney injury by recruiting BUD13 to regulate KEAP1/NRF2/HO-1 signaling pathway. J Inflamm (Lond) 2024 Sep 17;21(1):37.
    doi: 10.1186/s12950-024-00409-7pubmed: 39289683google scholar: lookup
  8. Li L, Li S, Ma H, Akhtar MF, Tan Y, Wang T, Liu W, Khan A, Khan MZ, Wang C. An Overview of Infectious and Non-Infectious Causes of Pregnancy Losses in Equine. Animals (Basel) 2024 Jul 2;14(13).
    doi: 10.3390/ani14131961pubmed: 38998073google scholar: lookup
Subscribe to our newsletter
Join 100,127 horse owners like you who receive our email updates on horse health and nutrition.