FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Animals : an open access journal from MDPI2020; 10(11); 2022; doi: 10.3390/ani10112022

Protective Effect of Silibinin on Lipopolysaccharide-Induced Inflammatory Responses in Equine Peripheral Blood Mononuclear Cells, an In Vitro Study.

Abstract: Although inflammation is an important physiological response, it plays a prominent role in several diseases across the mammalian species. In horses, in particular, inflammation secondary to bacterial infection or translocation is one of the most frequent causes of morbidity and mortality. Research in new molecules with anti-inflammatory and immunomodulatory proprieties and safe use profile is constantly an active field; natural compounds are an important source of molecules with peculiar properties such as antioxidants, anti-inflammatory and immune modulating. Silibinin, a natural polyphenolic flavonoid, extracted from plant milk thistle, has been reported to have actions such as antioxidant immunomodulatory and anti-inflammatory. The aim of this study was to test the effect of silibinin on lipopolysaccharide (LPS)-induced inflammatory response in equine peripheral blood mononuclear cells (PBMCs). Our results showed the protective effect of silibinin 10 μM and 50 μM in equine PBMCs stimulated with LPS. Silibilinin was able to prevent the LPS induced increased levels of TNF-α, IL-1β, IL-6 and IL-8. The results from this study on LPS-stimulated equine PBMCs showed that silibinin could be a useful pharmacological approach in treatment or prevention of several inflammatory conditions in horse.
Get Full Text
Publication Date: 2020-11-03 PubMed ID: 33153060PubMed Central: PMC7692186DOI: 10.3390/ani10112022Google 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

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 research attempts to determine the effects of silibinin, a compound derived from milk thistle, on inflammation in horses. The study found that silibinin was able to stave off inflammation, particularly from bacterial infections, suggesting this compound could be beneficial in preventing or treating several inflammatory conditions in horses.

Background

  • Inflammation, though a necessary physiological response, is a principal cause of numerous diseases among mammals and is often the result of bacterial infections. It is a particularly prevalent cause of morbidity and mortality in horses. As such, there is ongoing research into new molecules with anti-inflammatory and immune-modulating properties that are also safe for use.
  • Natural compounds are a significant area of investigation for such molecules. Silibinin, a polyphenolic flavonoid extracted from milk thistle, is one such compound. Previous studies have shown its potential as an antioxidant, immunomodulator, and anti-inflammatory agent, making it a candidate for medical uses.

Method and Results

  • This study’s aim was to test silibinin’s impact on inflammation induced by Lipopolysaccharides (LPS) in equine peripheral blood mononuclear cells (PBMCs). Animals’ PBMCs frequently serve as models in immunological studies, and LPS, often found in bacterial cell walls, are known to trigger strong immune responses.
  • Results indicated that silibinin had a protective effect on equine PBMCs stimulated with LPS. Specifically, treatment with 10 µM and 50 µM of silibinin was able to prevent increased levels of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8 which are typically induced by LPS.

Conclusion

  • The findings from this study suggest that silibinin could contribute to the prevention or treatment of various inflammatory conditions in horses by modulating the inflammatory response. By mitigating the LPS-induced inflammatory response, silibinin could potentially decrease the severity or incidence of diseases associated with inflammatory complications in horses.
  • However, more comprehensive studies would be necessary in order to fully understand the safety, efficacy, and application of silibinin in real-world scenarios.

Cite This Article

APA
Gugliandolo E, Crupi R, Biondi V, Licata P, Cuzzocrea S, Passantino A. (2020). Protective Effect of Silibinin on Lipopolysaccharide-Induced Inflammatory Responses in Equine Peripheral Blood Mononuclear Cells, an In Vitro Study. Animals (Basel), 10(11), 2022. https://doi.org/10.3390/ani10112022

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 10
Issue: 11
PII: 2022

Researcher Affiliations

Gugliandolo, Enrico
  • Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98166 Messina, Italy.
Crupi, Rosalia
  • Department of Veterinary Science, University of Messina, 98168 Messina, Italy.
Biondi, Vito
  • Department of Veterinary Science, University of Messina, 98168 Messina, Italy.
Licata, Patrizia
  • Department of Veterinary Science, University of Messina, 98168 Messina, Italy.
Cuzzocrea, Salvatore
  • Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98166 Messina, Italy.
  • Department of Pharmacological and Physiological Science, Saint Louis University, School of Medicine, 1402 South Grand Blvd, St Louis, MO 63104, USA.
Passantino, Annamaria
  • Department of Veterinary Science, University of Messina, 98168 Messina, Italy.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 39 references
  1. Moore JN, Vandenplas ML. Is it the systemic inflammatory response syndrome or endotoxemia in horses with colic?. Vet Clin North Am Equine Pract 2014 Aug;30(2):337-51, vii-viii.
    doi: 10.1016/j.cveq.2014.04.003pubmed: 25016495google scholar: lookup
  2. Taylor S. A review of equine sepsis.. Equine Vet Educ 2015 Feb;27(2):99-109.
    doi: 10.1111/eve.12290pmc: PMC7163761pubmed: 32313390google scholar: lookup
  3. Vinther AM, Skovgaard K, Heegaard PM, Andersen PH. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation.. BMC Vet Res 2015 Jun 16;11:134.
    doi: 10.1186/s12917-015-0450-5pmc: PMC4467047pubmed: 26076814google scholar: lookup
  4. Duz M, Marshall JF, Parkin TD. Proportion of nonsteroidal anti-inflammatory drug prescription in equine practice.. Equine Vet J 2019 Mar;51(2):147-153.
    doi: 10.1111/evj.12997pubmed: 30048005google scholar: lookup
  5. Lees P, Higgins AJ. Clinical pharmacology and therapeutic uses of non-steroidal anti-inflammatory drugs in the horse.. Equine Vet J 1985 Mar;17(2):83-96.
    doi: 10.1111/j.2042-3306.1985.tb02056.xpubmed: 3987667google scholar: lookup
  6. Ziegler A, Fogle C, Blikslager A. Update on the use of cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs in horses.. J Am Vet Med Assoc 2017 Jun 1;250(11):1271-1274.
    doi: 10.2460/javma.250.11.1271pmc: PMC5588883pubmed: 28509650google scholar: lookup
  7. Danner RL, Joiner KA, Rubin M, Patterson WH, Johnson N, Ayers KM, Parrillo JE. Purification, toxicity, and antiendotoxin activity of polymyxin B nonapeptide.. Antimicrob Agents Chemother 1989 Sep;33(9):1428-34.
    doi: 10.1128/AAC.33.9.1428pmc: PMC172678pubmed: 2554795google scholar: lookup
  8. Kim NC, Graf TN, Sparacino CM, Wani MC, Wall ME. Complete isolation and characterization of silybins and isosilybins from milk thistle (Silybum marianum).. Org Biomol Chem 2003 May 21;1(10):1684-9.
    doi: 10.1039/b300099kpubmed: 12926355google scholar: lookup
  9. Amato A, Terzo S, Mulè F. Natural Compounds as Beneficial Antioxidant Agents in Neurodegenerative Disorders: A Focus on Alzheimer's Disease.. Antioxidants (Basel) 2019 Nov 30;8(12).
    doi: 10.3390/antiox8120608pmc: PMC6943487pubmed: 31801234google scholar: lookup
  10. Esmaeil N, Anaraki SB, Gharagozloo M, Moayedi B. Silymarin impacts on immune system as an immunomodulator: One key for many locks.. Int Immunopharmacol 2017 Sep;50:194-201.
    doi: 10.1016/j.intimp.2017.06.030pubmed: 28672215google scholar: lookup
  11. Zheng W, Feng Z, Lou Y, Chen C, Zhang C, Tao Z, Li H, Cheng L, Ying X. Silibinin protects against osteoarthritis through inhibiting the inflammatory response and cartilage matrix degradation in vitro and in vivo.. Oncotarget 2017 Nov 21;8(59):99649-99665.
    doi: 10.18632/oncotarget.20587pmc: PMC5725122pubmed: 29245931google scholar: lookup
  12. Federico A, Dallio M, Loguercio C. Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years.. Molecules 2017 Jan 24;22(2).
    doi: 10.3390/molecules22020191pmc: PMC6155865pubmed: 28125040google scholar: lookup
  13. Raina K, Agarwal C, Agarwal R. Effect of silibinin in human colorectal cancer cells: targeting the activation of NF-κB signaling.. Mol Carcinog 2013 Mar;52(3):195-206.
    doi: 10.1002/mc.21843pmc: PMC3563833pubmed: 22086675google scholar: lookup
  14. Tian MY, Fan JH, Zhuang ZW, Dai F, Wang CY, Hou HT, Ma YZ. Effects of silymarin on p65 NF-κB, p38 MAPK and CYP450 in LPS-induced hoof dermal inflammatory cells of dairy cows.. BMC Vet Res 2019 Apr 30;15(1):127.
    doi: 10.1186/s12917-019-1868-ypmc: PMC6492397pubmed: 31039823google scholar: lookup
  15. Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G. Milk thistle extract and silymarin inhibit lipopolysaccharide induced lamellar separation of hoof explants in vitro.. Toxins (Basel) 2014 Oct 6;6(10):2962-74.
    doi: 10.3390/toxins6102962pmc: PMC4210879pubmed: 25290524google scholar: lookup
  16. Hackett ES, Mama KR, Twedt DC, Gustafson DL. Pharmacokinetics and safety of silibinin in horses.. Am J Vet Res 2013 Oct;74(10):1327-32.
    doi: 10.2460/ajvr.74.10.1327pubmed: 24066917google scholar: lookup
  17. Rütten S, Schrödl W, Abraham G. Modulation of TNF-α, IL-1Ra and IFN-γ in equine whole blood culture by glucocorticoids.. Vet Immunol Immunopathol 2019 Apr;210:1-5.
    doi: 10.1016/j.vetimm.2019.03.002pubmed: 30947974google scholar: lookup
  18. Squadrito F, Micali A, Rinaldi M, Irrera N, Marini H, Puzzolo D, Pisani A, Lorenzini C, Valenti A, Laurà R, Germanà A, Bitto A, Pizzino G, Pallio G, Altavilla D, Minutoli L. Polydeoxyribonucleotide, an Adenosine-A2(A) Receptor Agonist, Preserves Blood Testis Barrier from Cadmium-Induced Injury.. Front Pharmacol 2016;7:537.
    doi: 10.3389/fphar.2016.00537pmc: PMC5222826pubmed: 28119612google scholar: lookup
  19. Vendrig JC, Coffeng LE, Fink-Gremmels J. Equine colostral carbohydrates reduce lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells.. Equine Vet J Suppl 2012 Dec;(43):68-72.
    doi: 10.1111/j.2042-3306.2012.00680.xpubmed: 23447881google scholar: lookup
  20. Martin EM, Messenger KM, Sheats MK, Jones SL. Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes.. Front Vet Sci 2017;4:160.
    doi: 10.3389/fvets.2017.00160pmc: PMC5624997pubmed: 29034249google scholar: lookup
  21. Pizzino G, Irrera N, Bitto A, Pallio G, Mannino F, Arcoraci V, Aliquò F, Minutoli L, De Ponte C, D'andrea P, Squadrito F, Altavilla D. Cadmium-Induced Oxidative Stress Impairs Glycemic Control in Adolescents.. Oxid Med Cell Longev 2017;2017:6341671.
    doi: 10.1155/2017/6341671pmc: PMC5742892pubmed: 29379585google scholar: lookup
  22. MacKay RJ. Inflammation in horses.. Vet Clin North Am Equine Pract 2000 Apr;16(1):15-27, v.
    doi: 10.1016/S0749-0739(17)30116-5pubmed: 10752136google scholar: lookup
  23. de la Rebière de Pouyade G, Serteyn D. The role of activated neutrophils in the early stage of equine laminitis.. Vet J 2011 Jul;189(1):27-33.
    doi: 10.1016/j.tvjl.2010.06.008pubmed: 20655252google scholar: lookup
  24. Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity.. Immunity 2011 May 27;34(5):637-50.
    doi: 10.1016/j.immuni.2011.05.006pubmed: 21616434google scholar: lookup
  25. Gugliandolo E, Fusco R, Ginestra G, D'amico R, Bisignano C, Mandalari G, Cuzzocrea S, Di Paola R. Involvement of TLR4 and PPAR-α Receptors in Host Response and NLRP3 Inflammasome Activation, Against Pulmonary Infection With Pseudomonas Aeruginosa.. Shock 2019 Feb;51(2):221-227.
    doi: 10.1097/SHK.0000000000001137pubmed: 29547450google scholar: lookup
  26. Figueiredo MD, Vandenplas ML, Hurley DJ, Moore JN. Differential induction of MyD88- and TRIF-dependent pathways in equine monocytes by Toll-like receptor agonists.. Vet Immunol Immunopathol 2009 Jan 15;127(1-2):125-34.
    doi: 10.1016/j.vetimm.2008.09.028pubmed: 19019456google scholar: lookup
  27. Cudmore LA, Muurlink T, Whittem T, Bailey SR. Effects of oral clenbuterol on the clinical and inflammatory response to endotoxaemia in the horse.. Res Vet Sci 2013 Jun;94(3):682-6.
    doi: 10.1016/j.rvsc.2013.01.003pubmed: 23462621google scholar: lookup
  28. Werners AH. Treatment of endotoxaemia and septicaemia in the equine patient.. J Vet Pharmacol Ther 2017 Jan;40(1):1-15.
    doi: 10.1111/jvp.12329pubmed: 27452161google scholar: lookup
  29. Tomlinson JE, Wagner B, Felippe MJB, Van de Walle GR. Multispectral fluorescence-activated cell sorting of B and T cell subpopulations from equine peripheral blood.. Vet Immunol Immunopathol 2018 May;199:22-31.
    doi: 10.1016/j.vetimm.2018.03.010pubmed: 29678226google scholar: lookup
  30. Hue ES, Richard EA, Fortier CI, Fortier GD, Paillot R, Raue R, Pronost SL. Equine PBMC Cytokines Profile after In Vitro α- and γ-EHV Infection: Efficacy of a Parapoxvirus Ovis Based-Immunomodulator Treatment.. Vaccines (Basel) 2017 Sep 19;5(3).
    doi: 10.3390/vaccines5030028pmc: PMC5620559pubmed: 28925977google scholar: lookup
  31. Zholobenko A, Mouithys-Mickalad A, Modriansky M, Serteyn D, Franck T. Polyphenols from Silybum marianum inhibit in vitro the oxidant response of equine neutrophils and myeloperoxidase activity.. J Vet Pharmacol Ther 2016 Dec;39(6):592-601.
    doi: 10.1111/jvp.12319pubmed: 27213823google scholar: lookup
  32. Giorgi VS, Peracoli MT, Peracoli JC, Witkin SS, Bannwart-Castro CF. Silibinin modulates the NF-κb pathway and pro-inflammatory cytokine production by mononuclear cells from preeclamptic women.. J Reprod Immunol 2012 Sep;95(1-2):67-72.
    doi: 10.1016/j.jri.2012.06.004pubmed: 22871551google scholar: lookup
  33. Ngkelo A, Meja K, Yeadon M, Adcock I, Kirkham PA. LPS induced inflammatory responses in human peripheral blood mononuclear cells is mediated through NOX4 and Giα dependent PI-3kinase signalling.. J Inflamm (Lond) 2012 Jan 12;9(1):1.
    doi: 10.1186/1476-9255-9-1pmc: PMC3293082pubmed: 22239975google scholar: lookup
  34. Morris DD, Crowe N, Moore JN. Correlation of clinical and laboratory data with serum tumor necrosis factor activity in horses with experimentally induced endotoxemia.. Am J Vet Res 1990 Dec;51(12):1935-40.
    pubmed: 2085219
  35. Morris DD, Moore JN, Crowe N. Serum tumor necrosis factor activity in horses with colic attributable to gastrointestinal tract disease.. Am J Vet Res 1991 Oct;52(10):1565-9.
    pubmed: 1767972
  36. Tadros EM, Frank N. Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses.. Am J Vet Res 2012 Sep;73(9):1394-402.
    doi: 10.2460/ajvr.73.9.1394pubmed: 22924721google scholar: lookup
  37. Pusterla N, Magdesian KG, Mapes S, Leutenegger CM. Expression of molecular markers in blood of neonatal foals with sepsis.. Am J Vet Res 2006 Jun;67(6):1045-9.
    doi: 10.2460/ajvr.67.6.1045pubmed: 16740100google scholar: lookup
  38. Brooks AC, Rickards KJ, Cunningham FM. CXCL8 attenuates chemoattractant-induced equine neutrophil migration.. Vet Immunol Immunopathol 2011 Feb 15;139(2-4):141-7.
    doi: 10.1016/j.vetimm.2010.09.008pubmed: 21040981google scholar: lookup
  39. Sheats MK. A Comparative Review of Equine SIRS, Sepsis, and Neutrophils.. Front Vet Sci 2019;6:69.
    doi: 10.3389/fvets.2019.00069pmc: PMC6424004pubmed: 30931316google scholar: lookup

Citations

This article has been cited 8 times.
  1. Meng D, Wang Y, Liu T. Protective effects of silibinin on LPS-induced inflammation in human periodontal ligament cells. Front Chem 2022;10:1019663.
    doi: 10.3389/fchem.2022.1019663pubmed: 36300030google scholar: lookup
  2. Di Paola D, Iaria C, Capparucci F, Cordaro M, Crupi R, Siracusa R, D'Amico R, Fusco R, Impellizzeri D, Cuzzocrea S, Spanò N, Gugliandolo E, Peritore AF. Aflatoxin B1 Toxicity in Zebrafish Larva (Danio rerio): Protective Role of Hericium erinaceus. Toxins (Basel) 2021 Oct 8;13(10).
    doi: 10.3390/toxins13100710pubmed: 34679002google scholar: lookup
  3. Gour A, Manhas D, Bag S, Gorain B, Nandi U. Flavonoids as potential phytotherapeutics to combat cytokine storm in SARS-CoV-2. Phytother Res 2021 Aug;35(8):4258-4283.
    doi: 10.1002/ptr.7092pubmed: 33786876google scholar: lookup
  4. Urayama S, Muko R, Muranaka M, Mita H, Ohta M, Matsuda H, Tanaka A. Differential effects of flunixin meglumine and meloxicam on TNF- α production in LPS-stimulated equine neutrophils in vitro. Vet Anim Sci 2025 Dec;30:100513.
    doi: 10.1016/j.vas.2025.100513pubmed: 41078983google scholar: lookup
  5. Dong A, Zhang X, Ma J, Cao J, Diene G, Xu Y, Yin X, Li Y, Zhang Y. Silibinin Alleviates Liver Oxidative Stress in D-Galactose-Treated Kunming Mice via Microbiota Homeostasis in a Microbiota-Dependent Manner. Antioxidants (Basel) 2025 Sep 5;14(9).
    doi: 10.3390/antiox14091087pubmed: 41008993google scholar: lookup
  6. Ou JY, Liu SH, Tang DK, Shi LZ, Yan LJ, Huang JY, Zou LF, Quan JY, You YT, Chen YY, Yu LZ, Lu ZB. Protective Effect of Silibinin on Lipopolysaccharide-Induced Endotoxemia by Inhibiting Caspase-11-Dependent Cell Pyroptosis. Chin J Integr Med 2024 Oct;30(10):917-926.
    doi: 10.1007/s11655-024-3656-1pubmed: 38532152google scholar: lookup
  7. Surai PF, Surai A, Earle-Payne K. Silymarin and Inflammation: Food for Thoughts. Antioxidants (Basel) 2024 Jan 14;13(1).
    doi: 10.3390/antiox13010098pubmed: 38247522google scholar: lookup
  8. Tedesco DEA, Guerrini A. Use of Milk Thistle in Farm and Companion Animals: A Review. Planta Med 2023 May;89(6):584-607.
    doi: 10.1055/a-1969-2440pubmed: 36302565google scholar: lookup
Subscribe to our newsletter
Join 100,113 horse owners like you who receive our email updates on horse health and nutrition.