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2000
Volume 32, Issue 33
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Resveratrol (RES) is a phytochemical bioactive compound with suggested therapeutic benefits.

Objective

The current work aimed to evaluate the anti-inflammatory effect of RES against palmitate (PA) induced lipotoxicity in raw 264.7 macrophages cell line.

Methods

The cells viability was assessed by lactate dehydrogenase assay. Then the effects of RES and PA on nitric oxide (NO), triglyceride (TG) content, and cytokines release were studied. The effect of RES and PA on the treated cells bioenergetics and redox status was evaluated different assays.

Results

The results showed that at doses of 10 and 20 µM, RES dramatically increased the vitality of PA-exposed macrophages with dramatic significant decrease in the release the proinflammatory cytokines TNF-α, HMGB-1, IL-1β, and IL-6 and their coding genes expression with marked improvement in the cells phagocytic capacity. In addition, RES dramatically lowered the levels of NO and TG in PA-stimulated macrophages. In addition, PA markedly decreased mitochondrial complexes I and III activities with decreased mitochondrial membrane potential and lowered ATP production with induction of oxidative stress. RES was shown to mitigate the effect of PA on macrophages bioenergetics and the oxidative damage and counteracted PA effect on genes linked to oxidative damage, such as Nrf2, Ho-1, NF-κB p65, SOD1, and SOD2.

Conclusion

RES could reduce PA-induced lipotoxicity in macrophages enhancing their viability and counteracting the excess release of cytokines through alleviating PA-induced bioenergetic disruption and oxidative damage with a suggested positive impact of RES on obesity related illnesses caused by triggered cellular inflammation.

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References

  1. FengR. LuoC. LiC. DuS. OkekunleA.P. LiY. ChenY. ZiT. NiuY. Free fatty acids profile among lean, overweight and obese non-alcoholic fatty liver disease patients: A case – control study.Lipids Health Dis.201716116510.1186/s12944‑017‑0551‑128870233
     [Google Scholar]
  2. KhodabandehlooH. Gorgani-FiruzjaeeS. PanahiG. MeshkaniR. Molecular and cellular mechanisms linking inflammation to insulin resistance and β-cell dysfunction.Transl. Res.2016167122825610.1016/j.trsl.2015.08.01126408801
     [Google Scholar]
  3. SeifertE.L. EsteyC. XuanJ.Y. HarperM.E. Electron transport chain-dependent and -independent mechanisms of mitochondrial H2O2 emission during long-chain fatty acid oxidation.J. Biol. Chem.201028585748575810.1074/jbc.M109.02620320032466
     [Google Scholar]
  4. KorbeckiJ. Bajdak-RusinekK. The effect of palmitic acid on inflammatory response in macrophages: An overview of molecular mechanisms.Inflamm. Res.2019681191593210.1007/s00011‑019‑01273‑531363792
     [Google Scholar]
  5. ChenS. SaeedA.F.U.H. LiuQ. JiangQ. XuH. XiaoG.G. RaoL. DuoY. Macrophages in immunoregulation and therapeutics.Signal Transduct. Target. Ther.20238120710.1038/s41392‑023‑01452‑137211559
     [Google Scholar]
  6. MassE. NimmerjahnF. KierdorfK. SchlitzerA. Tissue-specific macrophages: How they develop and choreograph tissue biology.Nat. Rev. Immunol.202323956357910.1038/s41577‑023‑00848‑y36922638
     [Google Scholar]
  7. Justiz-VaillantA.A. Williams-PersadA.F.A. Arozarena-FundoraR. GopaulD. SoodeenS. Asin-MilanO. ThompsonR. UnakalC. AkpakaP.E. Chronic granulomatous disease (CGD): Commonly associated pathogens, diagnosis and treatment.Microorganisms2023119223310.3390/microorganisms1109223337764077
     [Google Scholar]
  8. NamgaladzeD. LipsS. LeikerT.J. MurphyR.C. EkroosK. FerreirosN. GeisslingerG. BrüneB. Inhibition of macrophage fatty acid β-oxidation exacerbates palmitate-induced inflammatory and endoplasmic reticulum stress responses.Diabetologia20145751067107710.1007/s00125‑014‑3173‑424488024
     [Google Scholar]
  9. TurJ. VicoT. LloberasJ. ZorzanoA. CeladaA. Macrophages and mitochondria.Adv. Immunol.201713313610.1016/bs.ai.2016.12.00128215277
     [Google Scholar]
  10. TannahillG.M. CurtisA.M. AdamikJ. Palsson-McDermottE.M. McGettrickA.F. GoelG. FrezzaC. BernardN.J. KellyB. FoleyN.H. ZhengL. GardetA. TongZ. JanyS.S. CorrS.C. HaneklausM. CaffreyB.E. PierceK. WalmsleyS. BeasleyF.C. CumminsE. NizetV. WhyteM. TaylorC.T. LinH. MastersS.L. GottliebE. KellyV.P. ClishC. AuronP.E. XavierR.J. O’NeillL.A.J. Succinate is an inflammatory signal that induces IL-1β through HIF-1α.Nature2013496744423824210.1038/nature1198623535595
     [Google Scholar]
  11. MillsE.L. KellyB. LoganA. CostaA.S.H. VarmaM. BryantC.E. TourlomousisP. DäbritzJ.H.M. GottliebE. LatorreI. CorrS.C. McManusG. RyanD. JacobsH.T. SziborM. XavierR.J. BraunT. FrezzaC. MurphyM.P. O’NeillL.A. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages.Cell20161672457470.e1310.1016/j.cell.2016.08.06427667687
     [Google Scholar]
  12. JhaA.K. HuangS.C.C. SergushichevA. LampropoulouV. IvanovaY. LoginichevaE. ChmielewskiK. StewartK.M. AshallJ. EvertsB. PearceE.J. DriggersE.M. ArtyomovM.N. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization.Immunity201542341943010.1016/j.immuni.2015.02.00525786174
     [Google Scholar]
  13. ZhongZ. UmemuraA. Sanchez-LopezE. LiangS. ShalapourS. WongJ. HeF. BoassaD. PerkinsG. AliS.R. McGeoughM.D. EllismanM.H. SekiE. GustafssonA.B. HoffmanH.M. Diaz-MecoM.T. MoscatJ. KarinM. NF-κB restricts inflammasome activation via elimination of damaged mitochondria.Cell2016164589691010.1016/j.cell.2015.12.05726919428
     [Google Scholar]
  14. TruongV.L. JunM. JeongW.S. Role of resveratrol in regulation of cellular defense systems against oxidative stress.Biofactors2018441364910.1002/biof.139929193412
     [Google Scholar]
  15. ShiY. ZhouJ. JiangB. MiaoM. Resveratrol and inflammatory bowel disease.Ann. N. Y. Acad. Sci.201714031384710.1111/nyas.1342628945937
     [Google Scholar]
  16. Bonnefont-RousselotD. Resveratrol and cardiovascular diseases.Nutrients20168525010.3390/nu805025027144581
     [Google Scholar]
  17. MattioL.M. DallavalleS. MussoL. FilardiR. FranzettiL. PellegrinoL. D’InceccoP. MoraD. PintoA. ArioliS. Antimicrobial activity of resveratrol-derived monomers and dimers against foodborne pathogens.Sci. Rep.2019911952510.1038/s41598‑019‑55975‑131862939
     [Google Scholar]
  18. KoJ.H. SethiG. UmJ.Y. ShanmugamM.K. ArfusoF. KumarA.P. BishayeeA. AhnK.S. The role of resveratrol in cancer therapy.Int. J. Mol. Sci.20171812258910.3390/ijms1812258929194365
     [Google Scholar]
  19. BaurJ.A. SinclairD.A. Therapeutic potential of resveratrol: The in vivo evidence.Nat. Rev. Drug Discov.20065649350610.1038/nrd206016732220
     [Google Scholar]
  20. NovelleM.G. WahlD. DiéguezC. BernierM. de CaboR. Resveratrol supplementation: Where are we now and where should we go?Ageing Res. Rev.20152111510.1016/j.arr.2015.01.00225625901
     [Google Scholar]
  21. OthmanR. AggourA. ElmorsyE. FawzyM.S. Nigella sativa, active principle thymoquinone, alleviates palmitate-induced cytotoxicity, inflammation and bioenergetic disruptions in macrophages: An invitro study model.Toxicon202424410775410.1016/j.toxicon.2024.10775438761922
     [Google Scholar]
  22. GreenL.C. WagnerD.A. GlogowskiJ. SkipperP.L. WishnokJ.S. TannenbaumS.R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids.Anal. Biochem.1982126113113810.1016/0003‑2697(82)90118‑X7181105
     [Google Scholar]
  23. SpinazziM. CasarinA. PertegatoV. SalviatiL. AngeliniC. Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells.Nat. Protoc.2012761235124610.1038/nprot.2012.05822653162
     [Google Scholar]
  24. ElmorsyE. ElzalabanyL.M. ElsheikhaH.M. SmithP.A. Adverse effects of antipsychotics on micro-vascular endothelial cells of the human blood–brain barrier.Brain Res.2014158325526810.1016/j.brainres.2014.08.01125139421
     [Google Scholar]
  25. AlamM.N. BristiN.J. RafiquzzamanM. Review on in vivo and in vitro methods evaluation of antioxidant activity.Saudi Pharm. J.201321214315210.1016/j.jsps.2012.05.00224936134
     [Google Scholar]
  26. BeauchampC. FridovichI. Superoxide dismutase: Improved assays and an assay applicable to acrylamide gels.Anal. Biochem.197144127628710.1016/0003‑2697(71)90370‑84943714
     [Google Scholar]
  27. SinghR. WisemanB. DeemagarnT. JhaV. SwitalaJ. LoewenP.C. Comparative study of catalase-peroxidases (KatGs).Arch. Biochem. Biophys.2008471220721410.1016/j.abb.2007.12.00818178143
     [Google Scholar]
  28. LiS. RenX. WangY. HuJ. WuH. SongS. YanC. Fucoxanthin alleviates palmitate-induced inflammation in RAW 264.7 cells through improving lipid metabolism and attenuating mitochondrial dysfunction.Food Funct.20201143361337010.1039/D0FO00442A32232236
     [Google Scholar]
  29. SergidesC. ChirilăM. SilvestroL. PittaD. PittasA. Bioavailability and safety study of resveratrol 500 mg tablets in healthy male and female volunteers.Exp. Ther. Med.201611116417010.3892/etm.2015.289526889234
     [Google Scholar]
  30. BoocockD.J. FaustG.E.S. PatelK.R. SchinasA.M. BrownV.A. DucharmeM.P. BoothT.D. CrowellJ.A. PerloffM. GescherA.J. StewardW.P. BrennerD.E. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent.Cancer Epidemiol. Biomarkers Prev.20071661246125210.1158/1055‑9965.EPI‑07‑002217548692
     [Google Scholar]
  31. KratzM. CoatsB.R. HisertK.B. HagmanD. MutskovV. PerisE. SchoenfeltK.Q. KuzmaJ.N. LarsonI. BillingP.S. LanderholmR.W. CrouthamelM. GozalD. HwangS. SinghP.K. BeckerL. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages.Cell Metab.201420461462510.1016/j.cmet.2014.08.01025242226
     [Google Scholar]
  32. BuckM.D. SowellR.T. KaechS.M. PearceE.L. Metabolic instruction of immunity.Cell2017169457058610.1016/j.cell.2017.04.00428475890
     [Google Scholar]
  33. LangstonP.K. ShibataM. HorngT. Metabolism supports macrophage activation.Front. Immunol.201786110.3389/fimmu.2017.0006128197151
     [Google Scholar]
  34. GaoX. XuY.X. JanakiramanN. ChapmanR.A. GautamS.C. Immunomodulatory activity of resveratrol: Suppression of lymphocyte proliferation, development of cell- mediated cytotoxicity, and cytokine production.Biochem. Pharmacol.20016291299130810.1016/S0006‑2952(01)00775‑411705464
     [Google Scholar]
  35. FuggettaM.P. BordignonV. CottarelliA. MacchiB. FrezzaC. Cordiali-FeiP. EnsoliF. CiafrèS. Marino-MerloF. MastinoA. RavagnanG. Downregulation of proinflammatory cytokines in HTLV-1-infected T cells by Resveratrol.J. Exp. Clin. Cancer Res.201635111810.1186/s13046‑016‑0398‑827448598
     [Google Scholar]
  36. ZouM. YangW. NiuL. SunY. LuoR. WangY. PengX. Polydatin attenuates Mycoplasma gallisepticum (HS strain)-induced inflammation injury via inhibiting the TLR6/MyD88/NF-κB pathway.Microb. Pathog.202014910455210.1016/j.micpath.2020.10455233010363
     [Google Scholar]
  37. JangM. CaiL. UdeaniG.O. SlowingK.V. ThomasC.F. BeecherC.W.W. FongH.H.S. FarnsworthN.R. KinghornA.D. MehtaR.G. MoonR.C. PezzutoJ.M. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.Science1997275529721822010.1126/science.275.5297.2188985016
     [Google Scholar]
  38. SimãoF. MattéA. PagnussatA.S. NettoC.A. SalbegoC.G. Resveratrol preconditioning modulates inflammatory response in the rat hippocampus following global cerebral ischemia.Neurochem. Int.201261565966510.1016/j.neuint.2012.06.00922709670
     [Google Scholar]
  39. HouY. ZhangY. MiY. WangJ. ZhangH. XuJ. YangY. LiuJ. DingL. YangJ. ChenG. WuC. A novel quinolyl-substituted analogue of resveratrol inhibits LPS-induced inflammatory responses in microglial cells by blocking the NF-κB/MAPK signaling pathways.Mol. Nutr. Food Res.20196320180138010.1002/mnfr.20180138031378007
     [Google Scholar]
  40. JiangH. DuanJ. XuK. ZhangW. Resveratrol protects against asthma-induced airway inflammation and remodeling by inhibiting the HMGB1/TLR4/NF-κB pathway.Exp. Ther. Med.201918145946610.3892/etm.2019.759431258683
     [Google Scholar]
  41. WangL. LiQ. YanH. JiaoG. WangH. ChiH. ZhouH. ChenL. ShanY. ChenY. Resveratrol protects osteoblasts against dexamethasone-induced cytotoxicity through activation of AMP-activated protein kinase.Drug Des. Devel. Ther.2020144451446310.2147/DDDT.S26650233122889
     [Google Scholar]
  42. LinT.K. ChenS.D. ChuangY.C. LinH.Y. HuangC.R. ChuangJ.H. WangP.W. HuangS.T. TiaoM.M. ChenJ.B. LiouC.W. Resveratrol partially prevents rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through induction of heme oxygenase-1 dependent autophagy.Int. J. Mol. Sci.20141511625164610.3390/ijms1501162524451142
     [Google Scholar]
  43. LinK.L. LinK.J. WangP.W. ChuangJ.H. LinH.Y. ChenS.D. ChuangY.C. HuangS.T. TiaoM.M. ChenJ.B. HuangP.H. LiouC.W. LinT.K. Resveratrol provides neuroprotective effects through modulation of mitochondrial dynamics and ERK1/2 regulated autophagy.Free Radic. Res.20185211-121371138610.1080/10715762.2018.148912830693838
     [Google Scholar]
  44. DasguptaB. MilbrandtJ. Resveratrol stimulates AMP kinase activity in neurons.Proc. Natl. Acad. Sci. USA2007104177217722210.1073/pnas.061006810417438283
     [Google Scholar]
  45. ChuangY.C. ChenS.D. HsuC.Y. ChenS.F. ChenN.C. JouS.B. Resveratrol promotes mitochondrial biogenesis and protects against seizure-induced neuronal cell damage in the hippocampus following status epilepticus by activation of the PGC-1α signaling pathway.Int. J. Mol. Sci.201920499810.3390/ijms2004099830823590
     [Google Scholar]
  46. SadiG. KonatD. Resveratrol regulates oxidative biomarkers and antioxidant enzymes in the brain of streptozotocin-induced diabetic rats.Pharm. Biol.20165471156116326079852
     [Google Scholar]
  47. ParkD.W. BaekK. KimJ.R. LeeJ.J. RyuS.H. ChinB.R. BaekS.H. Resveratrol inhibits foam cell formation via NADPH oxidase 1-mediated reactive oxygen species and monocyte chemotactic protein-1.Exp. Mol. Med.200941317117910.3858/emm.2009.41.3.02019293636
     [Google Scholar]
  48. BastianettoS. QuirionR. Heme oxygenase 1: Another possible target to explain the neuroprotective action of resveratrol, a multifaceted nutrient-based molecule.Exp. Neurol.2010225223723910.1016/j.expneurol.2010.06.01920603117
     [Google Scholar]
  49. SinhaK. DasJ. PalP.B. SilP.C. Oxidative stress: The mitochondria-dependent and mitochondria-independent pathways of apoptosis.Arch. Toxicol.20138771157118010.1007/s00204‑013‑1034‑423543009
     [Google Scholar]
  50. VringerE. TaitS.W.G. Mitochondria and inflammation: cell death heats up.Front. Cell Dev. Biol.2019710010.3389/fcell.2019.0010031316979
     [Google Scholar]
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Resveratrol Anti-inflammatory Effect against Palmitate-induced Cytotoxicity in Raw 264.7 Macrophages
Curr. Med. Chem. 32, 7406 (2025); https://doi.org/10.2174/0109298673352457241210083325
/content/journals/cmc/10.2174/0109298673352457241210083325
/content/journals/cmc/10.2174/0109298673352457241210083325
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  • Article Type:     Research Article
Keyword(s): Macrophages; mitochondria; obesity; oxidative damage; palmitate; resveratrol

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