Trends in Immunotherapy

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Effects of the Mongolian Medicine Eerdun Wurile on the Expression of Fas and FasL Post Retinal Ischemia‑Reperfusion Injury in Rat

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https://doi.org/10.54963/ti.v9i1.943
Li, C., Chultumsuren, Y., Bao, M., Sukhee, M., Byambajav, T., & Damdinjav, D. (2025). Effects of the Mongolian Medicine Eerdun Wurile on the Expression of Fas and FasL Post Retinal Ischemia‑Reperfusion Injury in Rat. Trends in Immunotherapy, 9(1), 68–78. https://doi.org/10.54963/ti.v9i1.943
Volume 9 Issue 1 (2025)
Copyright (c) 2025 ChangSheng Li, Yeruult Chultumsuren, Manjie Bao, Munkhbat Sukhee, Tserenlkham Byambajav, Davaadagva Damdinjav
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Authors

The purpose of this study is to examine how the traditional Mongolian medicine Eerdun Wurile affects Fas and FasL proteins following retinal ischemia-reperfusion injury (RIR) in rats. We used healthy adult rats (n=68) dividing them randomly into 5 groups: a control (n=4), a model (n=16), and three Eerdun Wurile treatment groups (n=16 each): high, medium, and low–dose group. The RIR rat model was created using the high intraocular pressure method. Eerdun Wurile was administered via gavage twice daily for a week prior to modeling, while the model group received a medium dose of normal saline. We utilized hematoxylin and eosin (HE) staining to observe retinal morphological changes under an optical microscope. Additionally, we employed immunohistochemical staining to determine how the treatment affected protein expression in the retinas of RIR rats. We observed that 24 hours after RIR, the retinal layers exhibited significant edema, disorganized structure, nuclear atrophy, and a substantial infiltration of inflammatory cells in the ganglion cell layer, accompanied by a reduction in ganglion cell count. As time progressed to 48 and 72 hours post-RIR, the retinal swelling gradually diminished, the retina became thinner, and numerous cells displayed vacuolation and nuclear condensation. Our findings suggest that Eerdun Wurile mitigates retinal cell damage caused by ischemia-reperfusion in rats by suppressing the expression of Fas and FasL proteins in rat retinal cells following RIR induction. Notably, the high-dose Eerdun Wurile group demonstrated significantly greater efficacy compared to the medium- and low-dose groups.

Keywords:

Mongolian Medicine Eerdun Wurile; Rats; Retinal Ischemia‑Reperfusion Injury; Fas; Fasl

References

  1. Ishizuka, F.; Shimazawa, M.; Umigai, N.; et al. Crocetin, a carotenoid derivative, inhibits retinal ischemic damage in mice. Eur. J. Pharmacol. 2013, 703, 1–10.
  2. Luo, H.; Zhuang, J.; Hu, P.; et al. Resveratrol delays retinal ganglion cell loss and attenuates gliosis‑related inflammation from ischemia‑reperfusion injury. Invest. Ophthalmol. Vis. Sci. 2018, 59, 3879–3888.
  3. Osborne, N.N.; Casson R.J.; Wood J.P.; et al. Retinal ischemia: Mechanisms of damage and potential therapeutic strategies. Prog. Retin. Eye Res. 2004, 23, 91–147.
  4. Cheon, E.W.; Park, C.H.; Kang, S.S.; et al. Change in endothelial nitric oxide synthase in the rat retina following transient ischemia. Neuroreport 2003, 14, 329–333.
  5. Hangai, M.; Yoshimura, N.; Hiroi, K.; et al. Inducible nitric oxide synthase in retinal ischemia‑reperfusion injury. Exp. Eye Res. 1996, 63, 501–509.
  6. Song, H.; Gao, D. Fasudil, a Rho‑associated protein kinase inhibitor, attenuates retinal ischemia and reperfusion injury in rats. Int. J. Mol. Med. 2011, 28, 193–198.
  7. Ko, M.L.; Chen, C.F.; Peng, P.H.; et al. Simvastatin upregulates Bcl‑2 expression and protects retinal neurons from early ischemia/reperfusion injury in the rat retina. Exp. Eye Res. 2011, 93, 580–585.
  8. Glukhova, X.A.; Trizna, J.A.; Proussakova, O.V.; et al. Impairment of Fas‑ligand‑caveolin‑1 interaction inhibits Fas‑ligand translocation to rafts and Fas‑ligand‑induced cell death. Cell Death Dis. 2018, 9, 73.
  9. Hao, L.N.; Zhang, Y.Q.; Shen, Y.H.; et al. Effect of puerarin on retinal pigment epithelial cells apoptosis induced partly by peroxynitrite via Fas/FasL pathway. Int. J. Ophthalmol. 2010, 3, 283–287.
  10. Sato, T.; Machida, T.; Takahashi, S.; et al. Fas‑mediated apoptosome formation is dependent on reactive oxygen species derived from mitochondrial permeability transition in Jurkat cells. J. Immunol. 2004, 173, 285–296.
  11. Li, C. Protective effects of traditional Mongolian medicine, Erdun‑wurile, on retina of rats after ischemia‑reperfusion injury. Stud. Inner Asian Hist. Cult. 2017, 3, 213.
  12. Carstens, E.; Moberg, G.P. Recognizing pain and distress in laboratory animals. ILAR J. 2000, 41, 62–71.
  13. Hartsock, M.J.; Cho, H.; Wu, L.; et al. A mouse model of retinal ischemia‑reperfusion injury through elevation of intraocular pressure. J. Vis. Exp. 2016, 54065.
  14. Zhang, H.J.; Xing, Y.Q.; Jin, W.; et al. Effects of curcumin on interleukin‑23 and interleukin‑17 expression in rat retina after retinal ischemia‑reperfusion injury. Int. J. Clin. Exp. Pathol. 2015, 8, 9223–9231.
  15. Goncalves, A.; Lin, C.M.; Muthusamy, A.; et al. Protective effect of a GLP‑1 analog on ischemia‑reperfusion induced blood‑retinal barrier breakdown and inϐlammation. Invest. Ophthalmol. Vis. Sci. 2016, 57, 2584–2592.
  16. Zhang, D.F.; Jiang, G.B.; Qin, C.Q.; et al. Quantitative assessment of the relationship between Fas/FasL genes polymorphisms and head and neck cancer risk. Medicine 2018, 97, e9873.
  17. Gregory, M.S.; Hackett, C.G.; Abernathy, E.F.; et al. Opposing roles for membrane bound and soluble Fas ligand in glaucoma‑associated retinal ganglion cell death. PLoS One 2011, 6, e17659.
  18. Eid, R.A.; Alkhateeb, M.A.; Eleawa, S.M.; et al. Fas/FasL‑mediated cell death in rat’s diabetic hearts involves activation of calcineurin/NFAT4 and is potentiated by a high‑fat diet rich in corn oil. J. Nutr. Biochem. 2019, 68, 79–90.
  19. Ju, K.R.; Kim, H.S.; Kim, J.H.; et al. Retinal glial cell responses and Fas/FasL activation in rats with chronic ocular hypertension. Brain Res. 2006, 1122, 209–221.
  20. Jia, Y.; Chen, X.; Chen, Y.; et al. Zhenbao Pill attenuates hydrogen peroxide‑induced apoptosis by inhibiting autophagy in human umbilical vein endothelial cells. J. Ethnopharmacol. 2021, 274, 114020.
  21. Qiao, Y.; Li, H.; Li, Y.; et al. Study on the mechanism of Eerdun Wurile’s effects on post‑operative cognitive dysfunction by the TLR4/NF‑kappaB pathway. Mol. Neurobiol. 2023, 60, 7274–7284.
  22. Li, Y.; Qiao, Y.; Li, H.; et al. Mechanism of the Mongolian medicine Eerdun Wurile basic formula in improving postoperative cognitive dysfunction by inhibiting apoptosis through the SIRT1/p53 signaling pathway. J. Ethnopharmacol. 2023, 309, 116312.
  23. Qiburi, Q.; Temuqile, T.; Baigude, H. Synergistic regulation of microglia gene expression by natural molecules in herbal medicine. Evid.‑Based Complement. Alternat. Med. 2021, 2021, 9920364.
  24. Huan, Y.; He, Y.; Liu, B.; et al. Zhenbao Pill reduces the percentage of Treg cells by inducing HSP27 expression. Biomed. Pharmacother. 2017, 96, 818–824.
  25. Qiburi, Q.; Ganbold, T.; Bao, Q.; et al. Bioactive components of ethnomedicine Eerdun Wurile regulate the transcription of pro‑inϐlammatory cytokines in microglia. J. Ethnopharmacol. 2020, 246, 112241.
  26. Wu, R.; Bao, Y.H. Protective effects of Eerduiwu Geriletu on rabbits’ retinal ischemia‑reperfusion injury. Mod. Chin. Med. Mater. Med. World Sci. Technol. 2008, 10, 125–128.
  27. Gaowa, S.; Bao, N.; Da, M.; et al. Traditional Mongolian medicine Eerdun Wurile improves stroke recovery through regulation of gene expression in rat brain. J. Ethnopharmacol. 2018, 222, 249–260.
  28. Wu, S.; Wu, R. Effects of Fas/Fasl, P53 protein expression in retinal ischemia‑reperfusion injury treated by Mongolian medicine Zhen‑Bao Pills. Mod. Chin. Med. Mater. Med. World Sci. Technol. 2011, 13, 888–893.
  29. Chang, J.R.; Xu, D.Q. Effects of formaldehyde on the activity of superoxide dismutases and glutathione peroxidase and the concentration of malondialdehyde. J. Hyg. Res. 2006, 35, 653–655.
  30. Li, C.S.; Chei, R. Effect of Mongolian medicine Erdun‑Wurile on NO and NOS in the serum of retinal ischemia‑reperfusion injury rats. J. Inner Mongolia Med. Univ. 2016, 568–571.
  31. Wu, X.L.; Tong, Q.; Hu, Y.R. Effects of Mongolian medicine Chagderi Pill on NO and NOS levels in the Brain and blood of rats with migraine. J. Inner Mongolia Univ. Natl. (Nat. Sci. Ed.) 2015, 515–517.