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2000
Volume 24, Issue 12
  • ISSN: 1871-5273
  • E-ISSN: 1996-3181

Abstract

Background

A major issue with neurodegenerative diseases is cholinergic depletion, the development of oxidative stress, and the reduction in the ability to control the expression of genes involved in the regulation of neurogenesis. The most widespread neurodegenerative disease is Alzheimer's disease (AD). Current treatments are not able to improve the symptoms of the disease. Thus, selecting or creating a safe and effective drug is very important.

Objective

In this context, the potential of sweroside (Swe) to regulate acetylcholinesterase (AChE) activity, malondialdehyde (MDA) level, and , , , and gene expression in the scopolamine (Sco)-induced zebrafish model of cognitive impairment was investigated.

Methods

Swe was administered daily for 16 days chronically to zebrafish at concentrations of 1 µg/L, 3 µg/L, and 5 µg/L whereas Sco (100 µM) was given to zebrafish for 30 min.

Results

Exposure to Swe decreased AChE activity and MDA level along with upregulating of gene expression in the brain of the Sco-induced zebrafish model.

Conclusion

Overall, our findings suggested that Swe has a positive role in the cholinergic system activity and brain antioxidant status and showed for the first time that it can restore the downregulated expression of , , , and genes in the brain of the Sco-induced zebrafish model.

© 2025 Bentham Science Publishers
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2025-02-06
2025-11-13

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References

  1. KnopmanD.S. AmievaH. PetersenR.C. Alzheimer disease.Nat. Rev. Dis. Primers2021713310.1038/s41572‑021‑00269‑y 33986301
     [Google Scholar]
  2. SundaramR. GowthamL. Microglia and regulation of inflammation-mediated neurodegeneration: Prevention and treatment by phytochemicals and metabolic nutrients.International Journal of Green Pharmacy201262819210.4103/0973‑8258.102807
     [Google Scholar]
  3. Ramos-RodriguezJ.J. Pacheco-HerreroM. ThyssenD. Rapid β-amyloid deposition and cognitive impairment after cholinergic denervation in APP/PS1 mice.J. Neuropathol. Exp. Neurol.201372427228510.1097/NEN.0b013e318288a8dd 23481704
     [Google Scholar]
  4. García-AyllónM.S. SmallD.H. AvilaJ. Sáez-ValeroJ. Revisiting the role of acetylcholinesterase in Alzheimer’s disease: cross-talk with P-tau and β-amyloid.Front. Mol. Neurosci.201142210.3389/fnmol.2011.00022 21949503
     [Google Scholar]
  5. FakhriS. PesceM. PatrunoA. Attenuation of Nrf2/Keap1/ARE in Alzheimer’s disease by plant secondary metabolites: A mechanistic review.Molecules20202521492610.3390/molecules25214926 33114450
     [Google Scholar]
  6. SykiotisG.P. BohmannD. Stress-activated cap’n’collar transcription factors in aging and human disease.Sci. Signal.20103112re310.1126/scisignal.3112re3 20215646
     [Google Scholar]
  7. MaQ. Role of nrf2 in oxidative stress and toxicity.Annu. Rev. Pharmacol. Toxicol.201353140142610.1146/annurev‑pharmtox‑011112‑140320 23294312
     [Google Scholar]
  8. TonelliC. ChioI.I.C. TuvesonD.A. Transcriptional regulation by Nrf2.Antioxid. Redox Signal.201829171727174510.1089/ars.2017.7342 28899199
     [Google Scholar]
  9. ShenG. JeongW.S. HuR. KongA.N.T. Regulation of Nrf2, NF-kappaB, and AP-1 signaling pathways by chemopreventive agents.Antioxid. Redox Signal.2005711-121648166310.1089/ars.2005.7.1648 16356127
     [Google Scholar]
  10. LandauG. KodaliV.K. MalhotraJ.D. KaufmanR.J. Detection of oxidative damage in response to protein misfolding in the endoplasmic reticulum.Methods Enzymol20135262315010.1016/B978‑0‑12‑405883‑5.00014‑4 23791104
     [Google Scholar]
  11. Colucci-D’AmatoL. SperanzaL. VolpicelliF. Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer.Int. J. Mol. Sci.20202120777710.3390/ijms21207777 33096634
     [Google Scholar]
  12. GøtzscheC.R. WoldbyeD.P.D. The role of NPY in learning and memory.Neuropeptides201655798910.1016/j.npep.2015.09.010 26454711
     [Google Scholar]
  13. GalloF.T. KatcheC. MoriciJ.F. MedinaJ.H. WeisstaubN.V. Immediate early genes, memory and psychiatric disorders: Focus on c-Fos, Egr1 and Arc.Front. Behav. Neurosci.2018127910.3389/fnbeh.2018.00079 29755331
     [Google Scholar]
  14. YangQ. YangF. GongJ. Sweroside ameliorates α-naphthylisothiocyanate-induced cholestatic liver injury in mice by regulating bile acids and suppressing pro-inflammatory responses.Acta Pharmacol. Sin.20163791218122810.1038/aps.2016.86 27498779
     [Google Scholar]
  15. WangJ. CaiX. MaR. LeiD. PanX. WangF. Anti-inflammatory effects of sweroside on LPS-induced ALI in mice via activating SIRT1.Inflammation20214451961196810.1007/s10753‑021‑01473‑4 33913051
     [Google Scholar]
  16. GongJ. YangF. YangQ. Sweroside ameliorated carbon tetrachloride (CCl4)-induced liver fibrosis through FXR-miR-29a signaling pathway.J. Nat. Med.2020741172510.1007/s11418‑019‑01334‑3 31280460
     [Google Scholar]
  17. YangG. JangJ.H. KimS.W. Sweroside prevents non-alcoholic steatohepatitis by suppressing activation of the NLRP3 inflammasome.Int. J. Mol. Sci.2020218279010.3390/ijms21082790 32316419
     [Google Scholar]
  18. HuangS. ZouC. XieS. Anticancer activity of sweroside nanoparticles in prostate cancer bone metastasis in PC-3 cells involved in Wnt/β -catenin signaling pathway.J. Biomed. Nanotechnol.202117101960197110.1166/jbn.2021.3172 34706796
     [Google Scholar]
  19. YangQ. ShuF. GongJ. Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response.J. Ethnopharmacol.202025511255610.1016/j.jep.2020.112556 31926984
     [Google Scholar]
  20. LiJ. ZhaoC. ZhuQ. Sweroside protects against myocardial Ischemia–reperfusion injury by inhibiting oxidative stress and pyroptosis partially via modulation of the Keap1/Nrf2 axis.Front. Cardiovasc. Med.2021865036810.3389/fcvm.2021.650368 33816579
     [Google Scholar]
  21. LiaoY. BaeH.J. ParkJ.H. Aster glehni extract ameliorates scopolamine-induced cognitive impairment in mice.J. Med. Food201922768569510.1089/jmf.2018.4302 31225769
     [Google Scholar]
  22. LvJ. LuC. JiangN. Protective effect of ginsenoside Rh2 on scopolamine-induced memory deficits through regulation of cho-linergic transmission, oxidative stress and the ERK-CREB-BDNF signaling pathway.Phytother. Res.202135133734510.1002/ptr.6804 32754961
     [Google Scholar]
  23. BrinzaI. RaeyM.A.E. El-KashakW. EldahshanO.A. HritcuL. Sweroside ameliorated memory deficits in scopolamine-induced zebrafish (Danio rerio) model: Involvement of cholinergic system and brain oxidative stress.Molecules20222718590110.3390/molecules27185901 36144637
     [Google Scholar]
  24. Percie du SertN. HurstV. AhluwaliaA. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research.PLoS Biol.2020187e300041010.1371/journal.pbio.3000410 32663219
     [Google Scholar]
  25. ValentimA.M. van EedenF.J. SträhleU. OlssonI.A.S. Euthanizing zebrafish legally in Europe.EMBO Rep.201617121688168910.15252/embr.201643153 27797854
     [Google Scholar]
  26. GuptaT. MullinsM.C. Dissection of organs from the adult zebrafish.J. Vis. Exp.2010171737171710.3791/1717‑v 20203557
     [Google Scholar]
  27. EllmanG.L. CourtneyK.D. AndresV.Jr FeatherstoneR.M. A new and rapid colorimetric determination of acetylcholinesterase activity.Biochem. Pharmacol.196172889510.1016/0006‑2952(61)90145‑9 13726518
     [Google Scholar]
  28. BradfordM.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal. Biochem.1976721-224825410.1016/0003‑2697(76)90527‑3 942051
     [Google Scholar]
  29. OhkawaH. OhishiN. YagiK. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal. Biochem.197995235135810.1016/0003‑2697(79)90738‑3 36810
     [Google Scholar]
  30. BoiangiuR.S. MihasanM. GorganD.L. StacheB.A. HritcuL. Anxiolytic, promnesic, anti-acetylcholinesterase and antioxidant effects of cotinine and 6-hydroxy-L-nicotine in scopolamine-induced zebrafish (Danio rerio) model of Alzheimer’s disease.Antioxidants202110221210.3390/antiox10020212 33535660
     [Google Scholar]
  31. ScofieldM.D. GardnerP.D. Molecular underpinnings of neuronal nicotinic acetylcholine receptor expression. LesterR Nicotinic Receptors The Receptors.New York, NY: Humana Press201426396010.1007/978‑1‑4939‑1167‑7_3
     [Google Scholar]
  32. FukushiY. GolanovE.V. KoizumiS. ThuraM. IharaH. YamamotoS. The cholinergic pathway and MitoKATP induce UCP4 expression involved in neuroprotection of FN stimulation in rats.Stroke Vasc. Intervent. Neurol.202226e00036210.1161/SVIN.122.000362
     [Google Scholar]
  33. RavichandranV.A. KimM. HanS.K. ChaY.S. Stachys sieboldii extract supplementation attenuates memory deficits by modulating BDNF-CREB and its downstream molecules, in animal models of memory impairment.Nutrients201810791710.3390/nu10070917 30018265
     [Google Scholar]
  34. WangR. DongZ. LanX. LiaoZ. ChenM. Sweroside alleviated LPS-induced inflammation via SIRT1 mediating NF-κB and FOXO1 signaling pathways in RAW264.7 cells.Molecules201924587210.3390/molecules24050872 30823686
     [Google Scholar]
  35. KhanH. Marya, Amin S, Kamal MA, Patel S. Flavonoids as acetylcholinesterase inhibitors: Current therapeutic standing and future prospects.Biomed. Pharmacother.201810186087010.1016/j.biopha.2018.03.007 29635895
     [Google Scholar]
  36. BekirJ. MarsM. SouchardJ.P. BouajilaJ. Assessment of antioxidant, anti-inflammatory, anti-cholinesterase and cytotoxic activities of pomegranate (Punica granatum) leaves.Food Chem. Toxicol.20135547047510.1016/j.fct.2013.01.036 23380204
     [Google Scholar]
  37. YangJ. ZhuD. JuB. JiangX. HuJ. Hepatoprotective effects of Gentianella turkestanerum extracts on acute liver injury induced by carbon tetrachloride in mice.Am. J. Transl. Res.201792569579 28337284
     [Google Scholar]
  38. MaL.Q. YuY. ChenH. Sweroside alleviated aconitine-induced cardiac toxicity in H9c2 cardiomyoblast cell line.Front. Pharmacol.20189113810.3389/fphar.2018.01138 30410440
     [Google Scholar]
  39. GaoL. ZhangY. SterlingK. SongW. Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential.Transl. Neurodegener.2022111410.1186/s40035‑022‑00279‑0 35090576
     [Google Scholar]
  40. KonarA. ShahN. SinghR. Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells.PLoS One2011611e2726510.1371/journal.pone.0027265 22096544
     [Google Scholar]
  41. KouY. LiZ. YangT. Therapeutic potential of plant iridoids in depression: A review.Pharm. Biol.20226012167218110.1080/13880209.2022.2136206 36300881
     [Google Scholar]
  42. SerdaMaciej. Bazı Gentianella Türlerinin Fitokimyasal Analizleri ve Sekonder Metabolitlerinin BDNF (Beyin-Türevli Nörotrofik Faktör) Üzerindeki Etkileri.Uniwersytet Śląski2022734335410.2/JQUERY.MIN.JS
     [Google Scholar]
  43. LiJ. DingX. ZhangR. Harpagoside ameliorates the amyloid-β-induced cognitive impairment in rats via up-regulating BDNF expression and MAPK/PI3K pathways.Neuroscience201530310311410.1016/j.neuroscience.2015.06.042 26135675
     [Google Scholar]
  44. ZhouZ. ZhuG. HaririA.R. Genetic variation in human NPY expression affects stress response and emotion.Nature20084527190997100110.1038/nature06858 18385673
     [Google Scholar]
  45. EgawaM. YoshimatsuH. BrayG.A. Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats.Am. J. Physiol. Regul. Integr. Comp. Physiol.19912602R328R33410.1152/ajpregu.1991.260.2.R328 1996720
     [Google Scholar]
  46. IshaqM. TranD. WuY. Asperuloside enhances taste perception and prevents weight gain in high-fat fed mice.Front. Endocrinol. (Lausanne)20211261544610.3389/fendo.2021.615446 33927690
     [Google Scholar]
  47. JonesM.W. ErringtonM.L. FrenchP.J. A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories.Nat. Neurosci.20014328929610.1038/85138 11224546
     [Google Scholar]
  48. HuY.T. ChenX.L. HuangS.H. Early growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer’s disease.Brain Pathol.201929450251210.1111/bpa.12688 30511454
     [Google Scholar]
  49. VeyracA. BesnardA. CabocheJ. DavisS. LarocheS. The transcription factor Zif268/Egr1, brain plasticity, and memory.Prog. Mol. Biol. Transl. Sci.20141228912910.1016/B978‑0‑12‑420170‑5.00004‑0 24484699
     [Google Scholar]
  50. HeF. RuX. WenT. NRF2, a transcription factor for stress response and beyond.Int. J. Mol. Sci.20202113477710.3390/ijms21134777 32640524
     [Google Scholar]
  51. HeT. ShenH. ZhuJ. Geniposide attenuates cadmium induced oxidative stress injury via Nrf2 signaling in osteoblasts.Mol. Med. Rep.20192021499150810.3892/mmr.2019.10396 31257486
     [Google Scholar]
  52. HanX.R. WenX. WangY.J. RETRACTED ARTICLE: Effects of CREB1 gene silencing on cognitive dysfunction by mediating PKA-CREB signaling pathway in mice with vascular dementia.Mol. Med.20182411810.1186/s10020‑018‑0020‑y 30134805
     [Google Scholar]
  53. RetinasamyT. ShaikhM.F. KumariY. OthmanI. OthmanI. Ethanolic extract of Orthosiphon stamineus improves memory in scopolamine-induced amnesia model.Front. Pharmacol.201910121610.3389/fphar.2019.01216 31736744
     [Google Scholar]
  54. WangM.Y. MengM. YangC. Cornel iridoid glycoside improves cognitive impairment induced by chronic cerebral hypoperfusion via activating PI3K/Akt/GSK-3β/CREB pathway in rats.Behav. Brain Res.202037911231910.1016/j.bbr.2019.112319 31669346
     [Google Scholar]
  55. RenL. ZhangH. TaoW. The rapid and long-lasting antidepressant effects of iridoid fraction in Gardenia Jasminoides J. Ellis are dependent on activating PKA-CREB signaling pathway.Front. Pharmacol.20221389662810.3389/fphar.2022.896628 35754496
     [Google Scholar]
  56. ZhangH. ZhaoC. LvC. Geniposide alleviates amyloid-induced synaptic injury by protecting axonal mitochondrial trafficking.Front. Cell. Neurosci.20171030910.3389/fncel.2016.00309 28179878
     [Google Scholar]
  57. DindaB. DindaM. KulsiG. ChakrabortyA. DindaS. Therapeutic potentials of plant iridoids in Alzheimer’s and Parkinson’s diseases: A review.Eur. J. Med. Chem.201916918519910.1016/j.ejmech.2019.03.009 30877973
     [Google Scholar]
/content/journals/cnsnddt/10.2174/0118715273345712250119200430
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Sweroside Modulates Oxidative Stress and Neuroplasticity-Related Gene Expression in Scopolamine-Treated Zebrafish
CNS Neurol. Disord. Drug Targets 24, 921 (2025); https://doi.org/10.2174/0118715273345712250119200430
/content/journals/cnsnddt/10.2174/0118715273345712250119200430
/content/journals/cnsnddt/10.2174/0118715273345712250119200430
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  • Article Type:     Research Article
Keyword(s): Alzheimer's disease; cholinergic system; Gene expression; neurogenesis; oxidative stress; scopolamine; sweroside; zebrafish

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