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.
Publication Date: 2025-07-17 PubMed ID: 40725115PubMed Central: PMC12295333DOI: 10.3390/ijms26146867Google 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.
- Journal Article
Cite This Article
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
Researcher Affiliations
- Department of Experimental Biology, Institute of Biology, Wrocław University of Environmental and Life Sciences, C. K. Norwida 25, 50-375 Wrocław, Poland.
- Department of Experimental Biology, Institute of Biology, Wrocław University of Environmental and Life Sciences, C. K. Norwida 25, 50-375 Wrocław, Poland.
- 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
- 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.
- 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.
- Dyson J. Practical management of equine metabolic syndrome.. Livestock 2014;19:186–193.
- Johnson PJ. The equine metabolic syndrome: Peripheral Cushing’s syndrome.. Vet. Clin. Equine Pract. 2002;18:271–293.
- Stefaniuk-Szmukier M, Piórkowska K, Ropka-Molik K. Equine metabolic syndrome: A complex disease influenced by multifactorial genetic factors.. Genes 2023;14:1544.
- Frank N, Geor RJ, Bailey S, Durham A, Johnson P. Equine metabolic syndrome.. J. Vet. Intern. Med. 2010;24:467–475.
- Geor RJ. Metabolic predispositions to laminitis in horses and ponies: Obesity, insulin resistance and metabolic syndromes.. J. Equine Vet. Sci. 2008;28:753–759.
- 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.
- 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.
- 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.
- 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.
- Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: An overview.. Sci. World J. 2013;2013:162750.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Sun X, Kaufman PD. Ki-67: More than a proliferation marker.. Chromosoma. 2018;127:175–186.
- 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.
- 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.
- 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.
- 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.
- Merrill BJ. Wnt pathway regulation of embryonic stem cell self-renewal.. Cold Spring Harb. Perspect. Biol. 2012;4:a007971.
- 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.
- Fu Y, Li H, Hao X. The self-renewal signaling pathways utilized by gastric cancer stem cells.. Tumor Biol. 2017;39:1010428317697577.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: An update.. Cell Transplant. 2016;25:829–848.
- Gugjoo MB, Sharma GT. Equine mesenchymal stem cells: Properties, sources, characterization, and potential therapeutic applications.. J. Equine Vet. Sci. 2019;72:16–27.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists