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Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
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Abstract

Background

Physalin B (PB) is one of the main active compounds of plants, with a wide range of biological activities. PB reportedly has the potential to treat Alzheimer’s disease (AD).

Objective

In this study, we investigated the effect of PB on Tau phosphorylation and cell apoptosis using Tau-expressing HEK293 cells (HEK293/Tau) as a cellular model.

Methods

The optimum concentration of PB to treat HEK293/Tau cells was determined using the CCK-8 assay. Additionally, the expression of FoxO1, Tau-5, p-Tau (T231, S262, and S404), ERK, p-ERK, GSK-3β, and p-GSK-3β was detected using western blotting to determine the effect of PB on Tau phosphorylation. The apoptosis rate was detected using flow cytometry, and the expression of Bax and Bcl-2 was detected using western blotting and verified using real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, cells were transfected with FoxO1 siRNA to downregulate FoxO1 expression, and the expression of the above-mentioned proteins was detected to verify the effect of PB on Tau phosphorylation and cell apoptosis.

Results

After 24 h of PB treatment, the phosphorylation levels of Tau at S404, S262, and T231 sites decreased significantly, and the activities of GSK-3β and ERK were inhibited. PB also reduced cell apoptosis by reducing the expression of Bax and increasing the expression of Bcl-2. In addition, PB decreased Tau phosphorylation and cell apoptosis by upregulating FoxO1.

Conclusion

The natural compound PB exhibited a protective effect in the AD cell model by increasing FoxO1 expression and reducing Tau phosphorylation and cell apoptosis.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2023-08-24
2024-11-23

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References

  1. CaiZ. ZhaoB. LiK. ZhangL. LiC. QuaziS.H. TanY. Mammalian target of rapamycin: A valid therapeutic target through the autophagy pathway for alzheimer’s disease?J. Neurosci. Res.20129061105111810.1002/jnr.2301122344941
     [Google Scholar]
  2. BrookmeyerR. KawasC.H. AbdallahN. Paganini-HillA. KimR.C. CorradaM.M. Impact of interventions to reduce Alzheimer’s disease pathology on the prevalence of dementia in the oldest‐old.Alzheimers Dement.201612322523210.1016/j.jalz.2016.01.00426900132
     [Google Scholar]
  3. BreijyehZ. KaramanR. Comprehensive review on alzheimer’s disease: Causes and treatment.Molecules20202524578910.3390/molecules2524578933302541
     [Google Scholar]
  4. VogelJ. AnandV.S. LudwigB. NawoschikS. DunlopJ. BraithwaiteS.P. The JNK pathway amplifies and drives subcellular changes in tau phosphorylation.Neuropharmacology2009575-653955010.1016/j.neuropharm.2009.07.02119628001
     [Google Scholar]
  5. RamananV.K. HeckmanM.G. LesnickT.G. PrzybelskiS.A. CahnE.J. KoselM.L. MurrayM.E. MielkeM.M. BothaH. Graff-RadfordJ. JonesD.T. LoweV.J. MachuldaM.M. JackC.R.Jr KnopmanD.S. PetersenR.C. RossO.A. VemuriP. Tau polygenic risk scoring: A cost-effective aid for prognostic counseling in Alzheimer’s disease.Acta Neuropathol.2022143557158310.1007/s00401‑022‑02419‑235412102
     [Google Scholar]
  6. WeingartenM.D. LockwoodA.H. HwoS.Y. KirschnerM.W. A protein factor essential for microtubule assembly.Proc. Natl. Acad. Sci.19757251858186210.1073/pnas.72.5.18581057175
     [Google Scholar]
  7. Tapia-RojasC. Cabezas-OpazoF. DeatonC. A. VergaraE. H. JohnsonG. V. W. QuintanillaR. A. It's all about tau.Prog. Neurobiol.2019175547610.1016/j.pneurobio.2018.12.005
     [Google Scholar]
  8. BarbierP. ZejneliO. MartinhoM. LasorsaA. BelleV. Smet-NoccaC. TsvetkovP. O. DevredF. LandrieuI. Role of tau as a microtubule-associated protein: Structural and functional aspects.Front. Aging. Neurosc.20191120410.3389/fnagi.2019.00204
     [Google Scholar]
  9. PotenteM. UrbichC. SasakiK. HofmannW.K. HeeschenC. AicherA. KolliparaR. DePinhoR.A. ZeiherA.M. DimmelerS. Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization.J. Clin. Invest.200511592382239210.1172/JCI2312616100571
     [Google Scholar]
  10. RaoR.R. LiQ. BuppM.R.G. ShrikantP.A. Transcription factor Foxo1 represses T-bet-mediated effector functions and promotes memory CD8(+) T cell differentiation.Immunity201236337438710.1016/j.immuni.2012.01.01522425248
     [Google Scholar]
  11. LiuL. BaiJ. LiuF. XuY. ZhaoM. ZhaoC. ZhouZ. Cross-talking pathways of forkhead Box O1 (FOXO1) are involved in the pathogenesis of alzheimer’s disease and huntington’s disease.Oxid. Med. Cell. Longev.2022202211410.1155/2022/761925535154571
     [Google Scholar]
  12. WuQ. YuanX. BaiJ. HanR. LiZ. ZhangH. XiuR. MicroRNA-181a protects against pericyte apoptosis via directly targeting FOXO1: Implication for ameliorated cognitive deficits in APP/PS1 mice.Aging201911166120613310.18632/aging.10217131467256
     [Google Scholar]
  13. WeiC. LiS. ZhuY. ChenW. LiC. XuR. Network pharmacology identify intersection genes of quercetin and Alzheimer’s disease as potential therapeutic targets.Front. Aging Neurosci.20221490209210.3389/fnagi.2022.90209236081896
     [Google Scholar]
  14. JenwitheesukA. BoontemP. WongchitratP. TocharusJ. MukdaS. GovitrapongP. Melatonin regulates the aging mouse hippocampal homeostasis via the sirtuin1-FOXO1 pathway.EXCLI J.20171634035310.17179/excli2016‑85228507478
     [Google Scholar]
  15. KuangX. ChenY.S. WangL.F. LiY.J. LiuK. ZhangM.X. LiL.J. ChenC. HeQ. WangY. DuJ.R. Klotho upregulation contributes to the neuroprotection of ligustilide in an Alzheimer’s disease mouse model.Neurobiol. Aging201435116917810.1016/j.neurobiolaging.2013.07.01923973442
     [Google Scholar]
  16. XiaE. XuF. HuC. KumalJ.P.P. TangX. MaoD. LiY. WuD. ZhangR. WuS. SunL. Young blood rescues the cognition of alzheimer’s model mice by restoring the hippocampal cholinergic circuit.Neuroscience2019417576910.1016/j.neuroscience.2019.08.01031404586
     [Google Scholar]
  17. ZhangW. BaiS. YangJ. ZhangY. LiuY. NieJ. MengD. ShiR. YaoZ. WangM. WangH. LiC. FoxO1 overexpression reduces Aβ production and tau phosphorylation in vitro.Neurosci. Lett.202073813532210.1016/j.neulet.2020.13532232860886
     [Google Scholar]
  18. AkramM. NawazA. Effects of medicinal plants on Alzheimer’s disease and memory deficits.Neural Regen. Res.201712466067010.4103/1673‑5374.20510828553349
     [Google Scholar]
  19. WuJ. ZhaoJ. ZhangT. GuY. KhanI.A. ZouZ. XuQ. Naturally occurring physalins from the genus Physalis: A review.Phytochemistry202119111292510.1016/j.phytochem.2021.11292534487922
     [Google Scholar]
  20. YangY.K. XieS. XuW. NianY. LiuX.L. PengX.R. DingZ.T. QiuM.H. Six new physalins from Physalis alkekengi var. franchetii and their cytotoxicity and antibacterial activity.Fitoterapia201611214415210.1016/j.fitote.2016.05.01027215128
     [Google Scholar]
  21. ZhangQ. XuN. HuX. ZhengY. Anti-colitic effects of Physalin B on dextran sodium sulfate-induced BALB/c mice by suppressing multiple inflammatory signaling pathways.J. Ethnopharmacol.202025911295610.1016/j.jep.2020.11295632442587
     [Google Scholar]
  22. CastroD.P. MoraesC.S. GonzalezM.S. RibeiroI.M. TomassiniT.C.B. AzambujaP. GarciaE.S. Physalin B inhibits Trypanosoma cruzi infection in the gut of Rhodnius prolixus by affecting the immune system and microbiota.J. Insect Physiol.201258121620162510.1016/j.jinsphys.2012.10.00123085484
     [Google Scholar]
  23. SáM.S. de MenezesM.N. KrettliA.U. RibeiroI.M. TomassiniT.C.B. Ribeiro dos SantosR. de AzevedoW.F.Jr SoaresM.B.P. Antimalarial activity of physalins B, D, F, and G.J. Nat. Prod.201174102269227210.1021/np200260f21954931
     [Google Scholar]
  24. WeiskirchenR. Physalin B attenuates liver fibrosis via suppressing LAP2α‐HDAC1 mediated deacetylation of glioma‐associated oncogene 1 and hepatic stellate cell activation.Br. J. Pharmacol.2021178204045404710.1111/bph.1558834409595
     [Google Scholar]
  25. ZhangW. BaiS.S. ZhangQ. ShiR.L. WangH.C. LiuY.C. NiT.J. WuY. YaoZ.Y. SunY. WangM.Y. Physalin B reduces Aβ secretion through down-regulation of BACE1 expression by activating FoxO1 and inhibiting STAT3 phosphorylation.Chin. J. Nat. Med.2021191073274010.1016/S1875‑5364(21)60090‑034688463
     [Google Scholar]
  26. FanJ.J. ZhengX.L. XiaH. TongY.C. LiuX. SunY. Chemical constituents from whole herb of Physalis angulata and their cytotoxic activity.Chin. Tradit. Herbal Drugs201748610801086
     [Google Scholar]
  27. HeB. ChenW. ZengJ. TongW. ZhengP. MicroRNA‐326 decreases tau phosphorylation and neuron apoptosis through inhibition of the JNK signaling pathway by targeting VAV1 in Alzheimer’s disease.J. Cell. Physiol.2020235148049310.1002/jcp.2898831385301
     [Google Scholar]
  28. PeiH. MaL. CaoY. WangF. LiZ. LiuN. LiuM. WeiY. LiH. Traditional chinese medicine for alzheimer’s disease and other cognitive impairment: A review.Am. J. Chin. Med.202048348751110.1142/S0192415X2050025132329645
     [Google Scholar]
  29. KaufmanS.K. Del TrediciK. ThomasT.L. BraakH. DiamondM.I. Tau seeding activity begins in the transentorhinal/entorhinal regions and anticipates phospho-tau pathology in Alzheimer’s disease and PART.Acta Neuropathol.20181361576710.1007/s00401‑018‑1855‑629752551
     [Google Scholar]
  30. WegmannS. BiernatJ. MandelkowE. A current view on Tau protein phosphorylation in Alzheimer's disease.Curr. Opin. Neurobiol.20216913113810.1016/j.conb.2021.03.003
     [Google Scholar]
  31. Turab NaqviA.A. HasanG.M. HassanM.I. Targeting tau hyperphosphorylation via Kinase Inhibition: Strategy to address alzheimer’s disease.Curr. Top. Med. Chem.202020121059107310.2174/156802662066620010612591031903881
     [Google Scholar]
  32. YanD. YaoJ. LiuY. ZhangX. WangY. ChenX. LiuL. ShiN. YanH. Tau hyperphosphorylation and P-CREB reduction are involved in acrylamide-induced spatial memory impairment: Suppression by curcumin.Brain. Behav. Immun.201871668010.1016/j.bbi.2018.04.014
     [Google Scholar]
  33. QiZ. ZhangY. YaoK. ZhangM. XuY. ZhangJ. BaiX. ZuH. dhcr24 knockdown lead to hyperphosphorylation of Tau at Thr181, Thr231, Ser262, Ser396, and Ser422 sites by membrane lipid-raft dependent PP2A signaling in SH-SY5Y cells.Neurochem. Res.20214671627164010.1007/s11064‑021‑03273‑633710538
     [Google Scholar]
  34. XiaoS. WuQ. YaoX. ZhangJ. ZhongW. ZhaoJ. LiuQ. ZhangM. Inhibitory effects of isobavachalcone on tau protein aggregation, tau phosphorylation, and oligomeric tau-induced apoptosis.ACS Chem. Neurosci.202112112313210.1021/acschemneuro.0c0061733320518
     [Google Scholar]
  35. ZhouC. JungC.G. KimM.J. WatanabeA. AbdelhamidM. TaslimaF. MichikawaM. Insulin deficiency increases sirt2 level in streptozotocin-treated alzheimer’s disease-like mouse model: Increased Sirt2 induces tau phosphorylation through ERK activation.Mol. Neurobiol.20225995408542510.1007/s12035‑022‑02918‑z35701718
     [Google Scholar]
  36. NilsonA.N. EnglishK.C. GersonJ.E. Barton WhittleT. Nicolas CrainC. XueJ. SenguptaU. Castillo-CarranzaD.L. ZhangW. GuptaP. KayedR. Tau oligomers associate with inflammation in the brain and retina of tauopathy mice and in neurodegenerative diseases.J. Alzheimers Dis.20165531083109910.3233/JAD‑16091227716675
     [Google Scholar]
  37. TolkovskyA.M. SpillantiniM.G. Tau aggregation and its relation to selected forms of neuronal cell death.Essays Biochem.202165784785710.1042/EBC2021003034897457
     [Google Scholar]
  38. ZhangM. WuQ. YaoX. ZhaoJ. ZhongW. LiuQ. XiaoS. Xanthohumol inhibits tau protein aggregation and protects cells against tau aggregates.Food Funct.201910127865787410.1039/C9FO02133G31793596
     [Google Scholar]
  39. SiddiquiW.A. AhadA. AhsanH. The mystery of BCL2 family: Bcl-2 proteins and apoptosis: An update.Arch. Toxicol.201589328931710.1007/s00204‑014‑1448‑725618543
     [Google Scholar]
  40. DlugoszP.J. BillenL.P. AnnisM.G. ZhuW. ZhangZ. LinJ. LeberB. AndrewsD.W. Bcl-2 changes conformation to inhibit Bax oligomerization.EMBO J.200625112287229610.1038/sj.emboj.760112616642033
     [Google Scholar]
  41. RemadeviV. MuraleedharanP. SreejaS. FOXO1: A pivotal pioneer factor in oral squamous cell carcinoma.Am. J. Cancer Res.202111104700471034765288
     [Google Scholar]
  42. ParoniG. SeripaD. FontanaA. D'OnofrioG. GravinaC. UrbanoM. CascavillaL. PellegriniF. GrecoA. PilottoA. FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer's disease.Clin. Interv. Aging.2014917839110.2147/CIA.S64758
     [Google Scholar]
  43. EstevezA.O. MorganK.L. SzewczykN.J. GemsD. EstevezM. The neurodegenerative effects of selenium are inhibited by FOXO and PINK1/PTEN regulation of insulin/insulin-like growth factor signaling in Caenorhabditis elegans.Neurotoxicology201441100284310.1016/j.neuro.2013.12.01224406377
     [Google Scholar]
  44. MaieseK. FoxO proteins in the nervous system.Anal. Cell. Pathol.2015201511510.1155/2015/56939226171319
     [Google Scholar]
  45. SantoE.E. PaikJ. FOXO in neural cells and diseases of the nervous system.Curr. Top. Dev. Biol.201812710511810.1016/bs.ctdb.2017.10.00229433734
     [Google Scholar]
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Physalin B Reduces Tau Phosphorylation and Cell Apoptosis in HEK293 Cells by Activating FoxO1
Curr Mol Pharmacol 17, e210723218991 (2024); https://doi.org/10.2174/1874467217666230721124057
/content/journals/cmp/10.2174/1874467217666230721124057
/content/journals/cmp/10.2174/1874467217666230721124057
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  • Article Type:     Research Article
Keyword(s): AD cell model; Alzheimer’s disease; Apoptosis; FoxO1; Physalin B; Tau phosphorylation

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