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International journal of molecular sciences2025; 26(14); 6867; doi: 10.3390/ijms26146867

Orientin Reverses Premature Senescence in Equine Adipose Stromal Cells Affected by Equine Metabolic Syndrome Through Oxidative Stress Modulation.

Abstract: Equine metabolic syndrome (EMS) is a prevalent endocrine disorder associated with insulin dysregulation, oxidative stress, and impaired regenerative capacity of adipose-derived stem cells (ASCs). The aim of this study was to evaluate the effects of orientin-a plant-derived flavonoid with known antioxidant properties-on equine ASCs (EqASCs) derived from both clinically healthy and diagnosed EMS-affected mares. EqASCs were treated with orientin to evaluate its biological effects. The analysis included key cellular functions such as proliferative capacity, viability, apoptosis, oxidative stress, senescence, clonogenicity, and migration. Orientin significantly enhanced the proliferative activity of EqASCs, as evidenced by increased Ki67 expression and favorable alterations in cell cycle distribution. In addition, the treatment improved overall cell viability, reduced apoptotic activity, and restored both the clonogenic potential and migratory capacity of the cells, with particularly pronounced effects observed in EqASCs isolated from EMS-affected horses. Importantly, orientin also led to a marked reduction in cellular senescence and oxidative stress, further suggesting its potential as a protective and regenerative agent in metabolically impaired ASCs. These findings indicate that orientin can exert comprehensive cytoprotective effects on EqASCs, with pronounced benefits in cells derived from EMS-affected animals. By improving multiple functional parameters, orientin emerges as a promising candidate for therapeutic strategies aimed at restoring the regenerative potential of ASCs compromised by metabolic dysregulation in horses.
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Publication Date: 2025-07-17 PubMed ID: 40725115PubMed Central: PMC12295333DOI: 10.3390/ijms26146867Google Scholar: Lookup
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APA
Orzoł D, Kępska M, Zyzak M. (2025). Orientin Reverses Premature Senescence in Equine Adipose Stromal Cells Affected by Equine Metabolic Syndrome Through Oxidative Stress Modulation. Int J Mol Sci, 26(14), 6867. https://doi.org/10.3390/ijms26146867

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 26
Issue: 14
PII: 6867

Researcher Affiliations

Orzoł, Dominika
  • Department of Experimental Biology, Institute of Biology, Wrocław University of Environmental and Life Sciences, C. K. Norwida 25, 50-375 Wrocław, Poland.
Kępska, Martyna
  • Department of Experimental Biology, Institute of Biology, Wrocław University of Environmental and Life Sciences, C. K. Norwida 25, 50-375 Wrocław, Poland.
Zyzak, Magdalena
  • Department of Experimental Biology, Institute of Biology, Wrocław University of Environmental and Life Sciences, C. K. Norwida 25, 50-375 Wrocław, Poland.

MeSH Terms

  • Animals
  • Horses
  • Oxidative Stress / drug effects
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / veterinary
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / pathology
  • Flavonoids / pharmacology
  • Cellular Senescence / drug effects
  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism
  • Glucosides / pharmacology
  • Cell Survival / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Apoptosis / drug effects
  • Horse Diseases / metabolism
  • Horse Diseases / drug therapy
  • Horse Diseases / pathology
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Cell Movement / drug effects
  • Cells, Cultured

Grant Funding

  • N010/0011/24 / Wrocu0142aw University of Environmental and Life Sciences

Conflict of Interest Statement

The authors declare no conflicts of interest.

References

This article includes 49 references
  1. Marycz K, Kornicka K, Basinska K, Czyrek A. Equine metabolic syndrome affects viability, senescence, and stress factors of equine adipose-derived mesenchymal stromal stem cells: New insight into EqASCs isolated from EMS horses in the context of their aging.. Oxidative Med. Cell Longev. 2016;2016:4710326.
    doi: 10.1155/2016/4710326pmc: PMC4670679pubmed: 26682006google scholar: lookup
  2. Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K. ECEIM consensus statement on equine metabolic syndrome.. J. Vet. Intern. Med. 2019;33:335–349.
    doi: 10.1111/jvim.15423pmc: PMC6430910pubmed: 30724412google scholar: lookup
  3. Dyson J. Practical management of equine metabolic syndrome.. Livestock 2014;19:186–193.
    doi: 10.12968/live.2014.19.3.186google scholar: lookup
  4. Johnson PJ. The equine metabolic syndrome: Peripheral Cushing’s syndrome.. Vet. Clin. Equine Pract. 2002;18:271–293.
    doi: 10.1016/S0749-0739(02)00006-8pubmed: 15635908google scholar: lookup
  5. Stefaniuk-Szmukier M, Piórkowska K, Ropka-Molik K. Equine metabolic syndrome: A complex disease influenced by multifactorial genetic factors.. Genes 2023;14:1544.
    doi: 10.3390/genes14081544pmc: PMC10454496pubmed: 37628596google scholar: lookup
  6. Frank N, Geor RJ, Bailey S, Durham A, Johnson P. Equine metabolic syndrome.. J. Vet. Intern. Med. 2010;24:467–475.
    doi: 10.1111/j.1939-1676.2010.0503.xpubmed: 20384947google scholar: lookup
  7. Geor RJ. Metabolic predispositions to laminitis in horses and ponies: Obesity, insulin resistance and metabolic syndromes.. J. Equine Vet. Sci. 2008;28:753–759.
    doi: 10.1016/j.jevs.2008.10.016google scholar: lookup
  8. McCue ME, Geor RJ, Schultz N. Equine metabolic syndrome: A complex disease influenced by genetics and the environment.. J. Equine Vet. Sci. 2015;35:367–375.
    doi: 10.1016/j.jevs.2015.03.004google scholar: lookup
  9. Fahmy MI, Sadek MA, Abdou K, El-Dessouki AM, El-Shiekh RA, Khalaf SS. Orientin: A comprehensive review of a promising bioactive flavonoid.. Inflammopharmacology 2025;33:1713–1728.
    doi: 10.1007/s10787-025-01690-5pmc: PMC11991976pubmed: 40056319google scholar: lookup
  10. Campisi J, d’Adda di Fagagna F. Cellular senescence: When bad things happen to good cells.. Nat. Rev. Mol. Cell Biol. 2007;8:729–740.
    doi: 10.1038/nrm2233pubmed: 17667954google scholar: lookup
  11. Loos CM, McLeod KR, Vanzant ES, Stratton SA, Bohannan AD, Coleman RJ, van Doorn DA, Urschel KL. Differential effect of two dietary protein sources on time course response of muscle anabolic signaling pathways in normal and insulin dysregulated horses.. Front. Vet. Sci. 2022;9:896220.
    doi: 10.3389/fvets.2022.896220pmc: PMC9376591pubmed: 35978710google scholar: lookup
  12. Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: An overview.. Sci. World J. 2013;2013:162750.
    doi: 10.1155/2013/162750pmc: PMC3891543pubmed: 24470791google scholar: lookup
  13. An F, Yang G, Tian J, Wang S. Antioxidant effects of the orientin and vitexin in Trollius chinensis Bunge in D-galactose-aged mice.. Neural Regen. Res. 2012;7:2565–2575.
    pmc: PMC4200723pubmed: 25368632
  14. Tchkonia T, Morbeck DE, Von Zglinicki T, Van Deursen J, Lustgarten J, Scrable H, Khosla S, Jensen MD, Kirkland JL. Fat tissue, aging, and cellular senescence.. Aging Cell. 2010;9:667–684.
    doi: 10.1111/j.1474-9726.2010.00608.xpmc: PMC2941545pubmed: 20701600google scholar: lookup
  15. Kornicka K, Śmieszek A, Szłapka-Kosarzewska J, Irwin Houston JM, Roecken M, Marycz K. Characterization of apoptosis, autophagy and oxidative stress in pancreatic islets cells and intestinal epithelial cells isolated from equine metabolic syndrome (EMS) horses.. Int. J. Mol. Sci. 2018;19:3068.
    doi: 10.3390/ijms19103068pmc: PMC6212973pubmed: 30297648google scholar: lookup
  16. Liu J, Ding Y, Liu Z, Liang X. Senescence in mesenchymal stem cells: Functional alterations, molecular mechanisms, and rejuvenation strategies.. Front. Cell Dev. Biol. 2020;8:258.
    doi: 10.3389/fcell.2020.00258pmc: PMC7232554pubmed: 32478063google scholar: lookup
  17. Salminen A, Kaarniranta K. Control of p53 and NF-κB signaling by WIP1 and MIF: Role in cellular senescence and organismal aging.. Cell Signal. 2011;23:747–752.
    doi: 10.1016/j.cellsig.2010.10.012pubmed: 20940041google scholar: lookup
  18. Coppe JP, Patil CK, Rodier F, Krtolica A, Beausejour CM, Parrinello S, Hodgson JG, Chin K, Desprez PY, Campisi J. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen.. PLoS ONE. 2010;5:e9188.
    doi: 10.1371/journal.pone.0009188pmc: PMC2820538pubmed: 20169192google scholar: lookup
  19. Zak A, Siwinska N, Elzinga S, Barker V, Stefaniak T, Schanbacher B, Place N, Niedzwiedz A, Adams A. Effects of equine metabolic syndrome on inflammation and acute-phase markers in horses.. Domest. Anim. Endocrinol. 2020;72:106448.
    doi: 10.1016/j.domaniend.2020.106448pubmed: 32247989google scholar: lookup
  20. Chen H, Liu S, Xing J, Wen Y, Chen L. Orientin alleviates chondrocyte senescence and osteoarthritis by inhibiting PI3K/AKT pathway.. Bone Jt. Res. 2025;14:245–258.
    doi: 10.1302/2046-3758.143.BJR-2023-0383.R2pmc: PMC11908465pubmed: 40085067google scholar: lookup
  21. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.. J. Immunol. 1984;133:1710–1715.
    doi: 10.4049/jimmunol.133.4.1710pubmed: 6206131google scholar: lookup
  22. Sun X, Kaufman PD. Ki-67: More than a proliferation marker.. Chromosoma. 2018;127:175–186.
    doi: 10.1007/s00412-018-0659-8pmc: PMC5945335pubmed: 29322240google scholar: lookup
  23. Thangaraj K, Balasubramanian B, Park S, Natesan K, Liu W, Manju V. Orientin induces G0/G1 cell cycle arrest and mitochondria mediated intrinsic apoptosis in human colorectal carcinoma HT29 cells.. Biomolecules. 2019;9:418.
    doi: 10.3390/biom9090418pmc: PMC6770649pubmed: 31461995google scholar: lookup
  24. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells.. Mol. Biol. Cell. 2002;13:4279–4295.
    doi: 10.1091/mbc.e02-02-0105pmc: PMC138633pubmed: 12475952google scholar: lookup
  25. Vidal MA, Kilroy GE, Lopez MJ, Johnson JR, Moore RM, Gimble JM. Characterization of equine adipose tissue-derived stromal cells: Adipogenic and osteogenic capacity and comparison with bone marrow-derived mesenchymal stromal cells.. Vet. Surg. 2007;36:613–622.
    doi: 10.1111/j.1532-950X.2007.00313.xpubmed: 17894587google scholar: lookup
  26. Nusse R, Fuerer C, Ching W, Harnish K, Logan C, Zeng A, Ten Berge D, Kalani Y. Cold Spring Harbor Symposia On Quantitative Biology.. Cold Spring Harbor Laboratory Press; New York, NY, USA: 2008. pp. 59–66.
    pubmed: 19028988
  27. Merrill BJ. Wnt pathway regulation of embryonic stem cell self-renewal.. Cold Spring Harb. Perspect. Biol. 2012;4:a007971.
    doi: 10.1101/cshperspect.a007971pmc: PMC3428775pubmed: 22952393google scholar: lookup
  28. Xu Z, Robitaille AM, Berndt JD, Davidson KC, Fischer KA, Mathieu J, Potter JC, Ruohola-Baker H, Moon RT. Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells.. Proc. Natl. Acad. Sci. USA. 2016;113:E6382–E6390.
    doi: 10.1073/pnas.1613849113pmc: PMC5081574pubmed: 27698112google scholar: lookup
  29. Fu Y, Li H, Hao X. The self-renewal signaling pathways utilized by gastric cancer stem cells.. Tumor Biol. 2017;39:1010428317697577.
    doi: 10.1177/1010428317697577pubmed: 28378630google scholar: lookup
  30. Semba T, Sammons R, Wang X, Xie X, Dalby KN, Ueno NT. JNK signaling in stem cell self-renewal and differentiation.. Int. J. Mol. Sci. 2020;21:2613.
    doi: 10.3390/ijms21072613pmc: PMC7177258pubmed: 32283767google scholar: lookup
  31. Vasudevan Sajini D, Thaggikuppe Krishnamurthy P, Chakkittukandiyil A, Mudavath RN. Orientin Modulates Nrf2-ARE, PI3K/Akt, JNK-ERK1/2, and TLR4/NF-kB Pathways to Produce Neuroprotective Benefits in Parkinson’s Disease.. Neurochem. Res. 2024;49:1577–1587.
    doi: 10.1007/s11064-024-04099-8pubmed: 38276990google scholar: lookup
  32. Yuan TJ, Xu XH, Zhou N, Yan G, Gu TW, Peng LH. Phytochemicals as new therapeutic candidates simultaneously stimulate proliferation and counteract senescence of stem cells.. Biomed. Pharmacother. 2022;151:113170.
    doi: 10.1016/j.biopha.2022.113170pubmed: 35676782google scholar: lookup
  33. Ji W, Xu W. Orientin inhibits the progression of fibroblast-like synovial cells in rheumatoid arthritis by regulating MAPK-signaling pathway.. Allergol. Immunopathol. 2022;50:154–162.
    pubmed: 36335459
  34. Kim SJ, Pham TH, Bak Y, Ryu HW, Oh SR, Yoon DY. Orientin inhibits invasion by suppressing MMP-9 and IL-8 expression via the PKCα/ERK/AP-1/STAT3-mediated signaling pathways in TPA-treated MCF-7 breast cancer cells.. Phytomedicine. 2018;50:35–42.
    doi: 10.1016/j.phymed.2018.09.172pubmed: 30466990google scholar: lookup
  35. Hora AB, Biano LS, Nascimento ACS, Camargo ZT, Heiden GI, Albulquerque-Júnior RL, Grespan R, Aragão JM, Camargo EA. Isoorientin Improves Excisional Skin Wound Healing in Mice.. Pharmaceuticals. 2024;17:1368.
    doi: 10.3390/ph17101368pmc: PMC11510251pubmed: 39459009google scholar: lookup
  36. Che Zain MS, Lee SY, Sarian MN, Fakurazi S, Shaari K. In Vitro wound healing potential of flavonoid c-glycosides from oil palm (Elaeis guineensis Jacq.) leaves on 3t3 fibroblast cells.. Antioxidants. 2020;9:326.
    doi: 10.3390/antiox9040326pmc: PMC7222399pubmed: 32316665google scholar: lookup
  37. Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: An update.. Cell Transplant. 2016;25:829–848.
    doi: 10.3727/096368915X689622pubmed: 26423725google scholar: lookup
  38. Gugjoo MB, Sharma GT. Equine mesenchymal stem cells: Properties, sources, characterization, and potential therapeutic applications.. J. Equine Vet. Sci. 2019;72:16–27.
    doi: 10.1016/j.jevs.2018.10.007pubmed: 30929778google scholar: lookup
  39. Marycz K, Weiss C, Śmieszek A, Kornicka K. Evaluation of oxidative stress and mitophagy during adipogenic differentiation of adipose-derived stem cells isolated from equine metabolic syndrome (EMS) horses.. Stem Cells Int. 2018;2018:5340756.
    doi: 10.1155/2018/5340756pmc: PMC6011082pubmed: 29977307google scholar: lookup
  40. Xiao Q, Piao R, Wang H, Li C, Song L. Orientin-mediated Nrf2/HO-1 signal alleviates H2O2-induced oxidative damage via induction of JNK and PI3K/AKT activation.. Int. J. Biol. Macromol. 2018;118:747–755.
    doi: 10.1016/j.ijbiomac.2018.06.130pubmed: 29959995google scholar: lookup
  41. Li F, Zong J, Zhang H, Zhang P, Xu L, Liang K, Yang L, Yong H, Qian W. Orientin reduces myocardial infarction size via eNOS/NO signaling and thus mitigates adverse cardiac remodeling.. Front. Pharmacol. 2017;8:926.
    doi: 10.3389/fphar.2017.00926pmc: PMC5742593pubmed: 29311930google scholar: lookup
  42. Liang Y, Li J, Lin Q, Huang P, Zhang L, Wu W, Ma Y. Research progress on signaling pathway-associated oxidative stress in endothelial cells.. Oxidative Med. Cell Longev. 2017;2017:7156941.
    doi: 10.1155/2017/7156941pmc: PMC5414589pubmed: 28503253google scholar: lookup
  43. Xiao Q, Cui Y, Zhao Y, Liu L, Wang H, Yang L. Orientin relieves lipopolysaccharide-induced acute lung injury in mice: The involvement of its anti-inflammatory and anti-oxidant properties.. Int. Immunopharmacol. 2021;90:107189.
    doi: 10.1016/j.intimp.2020.107189pubmed: 33214095google scholar: lookup
  44. Fukui M, Zhu BT. Mitochondrial superoxide dismutase SOD2, but not cytosolic SOD1, plays a critical role in protection against glutamate-induced oxidative stress and cell death in HT22 neuronal cells.. Free Radic. Biol. Med. 2010;48:821–830.
    doi: 10.1016/j.freeradbiomed.2009.12.024pmc: PMC2861908pubmed: 20060889google scholar: lookup
  45. Li F, Liao X, Jiang L, Zhao J, Wu S, Ming J. Orientin attenuated d-GalN/LPS-induced liver injury through the inhibition of oxidative stress via nrf2/keap1 pathway.. J. Agric. Food Chem. 2022;70:7953–7967.
    doi: 10.1021/acs.jafc.2c02015pubmed: 35729734google scholar: lookup
  46. Qu Y, Shi L, Liu Y, Huang L, Luo HR, Wu GS. Orientin prolongs the longevity of caenorhabditis elegans and postpones the development of neurodegenerative diseases via nutrition sensing and cellular protective pathways.. Oxidative Med. Cell Longev. 2022;2022:8878923.
    doi: 10.1155/2022/8878923pmc: PMC8885179pubmed: 35237385google scholar: lookup
  47. Fan H, Wang L, Zhao K, Li N, Shi Z, Ge Z, Jin Z. Fabrication, mechanical properties, and biocompatibility of graphene-reinforced chitosan composites.. Biomacromolecules. 2010;11:2345–2351.
    doi: 10.1021/bm100470qpubmed: 20687549google scholar: lookup
  48. Bourebaba L, Zyzak M, Sikora M, Serwotka-Suszczak A, Mularczyk M, Al Naem M, Marycz K. Sex hormone-binding globulin (SHBG) maintains proper equine adipose-derived stromal cells (ASCs)’ Metabolic functions and negatively regulates their basal adipogenic potential.. Stem Cell Rev. Rep. 2023;19:2251–2273.
    doi: 10.1007/s12015-023-10580-8pmc: PMC10579166pubmed: 37402098google scholar: lookup
  49. Frazier TP, Gimble JM, Devay JW, Tucker HA, Chiu ES, Rowan BG. Body mass index affects proliferation and osteogenic differentiation of human subcutaneous adipose tissue-derived stem cells.. BMC Cell Biol. 2013;14:34.
    doi: 10.1186/1471-2121-14-34pmc: PMC3750383pubmed: 23924189google scholar: lookup

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