Skip to content
2000
Volume 21, Issue 4
  • ISSN: 1567-2050
  • E-ISSN: 1875-5828

Abstract

Background

Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic.

Objectives

We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.

Methods

AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.

Results

In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.

Conclusion

Arctiin can enhance rats’ behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-β. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.

Loading

Article metrics loading...

/content/journals/car/10.2174/0115672050333388240801043509
2024-04-01
2024-11-21
Loading full text...

Full text loading...

References

  1. 2023 Alzheimer’s disease facts and figures.Alzheimers Dement.20231941598169510.1002/alz.1301636918389
    [Google Scholar]
  2. Tahami MonfaredA.A. ByrnesM.J. WhiteL.A. ZhangQ. Alzheimer’s Disease: Epidemiology and clinical progression.Neurol. Ther.202211255356910.1007/s40120‑022‑00338‑835286590
    [Google Scholar]
  3. TripathiP.N. SrivastavaP. SharmaP. TripathiM.K. SethA. TripathiA. RaiS.N. SinghS.P. ShrivastavaS.K. Biphenyl-3-oxo-1,2,4-triazine linked piperazine derivatives as potential cholinesterase inhibitors with anti-oxidant property to improve the learning and memory.Bioorg. Chem.201985829610.1016/j.bioorg.2018.12.01730605887
    [Google Scholar]
  4. SrivastavaP. TripathiP.N. SharmaP. RaiS.N. SinghS.P. SrivastavaR.K. ShankarS. ShrivastavaS.K. Design and development of some phenyl benzoxazole derivatives as a potent acetylcholinesterase inhibitor with antioxidant property to enhance learning and memory.Eur. J. Med. Chem.201916311613510.1016/j.ejmech.2018.11.04930503937
    [Google Scholar]
  5. MasurkarP.P. ChatterjeeS. ShererJ.T. ChenH. JohnsonM.L. AparasuR.R. Risk of serious adverse events associated with individual cholinesterase inhibitors use in older adults with dementia: A population-based cohort study.Drugs Aging202239645346510.1007/s40266‑022‑00944‑z35666463
    [Google Scholar]
  6. TangB.C. WangY.T. RenJ. Basic information about memantine and its treatment of Alzheimer’s disease and other clinical applications.Ibrain20239334034810.1002/ibra.1209837786758
    [Google Scholar]
  7. CalsolaroV. FemminellaG.D. RoganiS. EspositoS. FranchiR. OkoyeC. RengoG. MonzaniF. Behavioral and psychological symptoms in dementia (BPSD) and the use of antipsychotics.Pharmaceuticals (Basel)202114324610.3390/ph1403024633803277
    [Google Scholar]
  8. HuangL.K. KuanY.C. LinH.W. HuC.J. Clinical trials of new drugs for Alzheimer disease: A 2020–2023 update.J. Biomed. Sci.20233018310.1186/s12929‑023‑00976‑637784171
    [Google Scholar]
  9. RaiS.N. SinghC. SinghA. SinghM.P. SinghB.K. Mitochondrial dysfunction: A potential therapeutic target to treat alzheimer’s disease.Mol. Neurobiol.20205773075308810.1007/s12035‑020‑01945‑y32462551
    [Google Scholar]
  10. SinghM. AgarwalV. PanchamP. JindalD. AgarwalS. RaiS. SinghS. GuptaV. A comprehensive review and androgen deprivation therapy and its impact on alzheimer’s disease risk in older men with prostate cancer.Degener. Neurol. Neuromuscul. Dis.202414334610.2147/DNND.S44513038774717
    [Google Scholar]
  11. TripathiP. LodhiA. RaiS. NandiN. DumogaS. YadavP. TiwariA. SinghS. El-ShorbagiA.N. ChaudharyS. Review of pharmacotherapeutic targets in alzheimer’s disease and its management using traditional medicinal plants.Degener. Neurol. Neuromuscul. Dis.202414477410.2147/DNND.S45200938784601
    [Google Scholar]
  12. AlshehriS.A. AlmarwaniW.A. AlbalawiA.Z. Al-atwiS.M. AljohaniK.K. AlanaziA.A. EbrahimM.A. HassanH.M. Al-GayyarM.M. Role of arctiin in fibrosis and apoptosis in experimentally induced hepatocellular carcinoma in rats.Cureus2024161e5199710.7759/cureus.5199738205087
    [Google Scholar]
  13. AlfairB.M. JabartiA.A. AlbalawiS.S. KhodirA.E. Al-GayyarM.M. Arctiin inhibits inflammation, fibrosis, and tumor cell migration in rats with ehrlich solid carcinoma.Cureus2023159e4498710.7759/cureus.4498737701157
    [Google Scholar]
  14. AlharbiKM. AlshehriSA. AlmarwaniWA. Effects of cycloastragenol on alzheimer's disease in rats by reducing oxidative stress, inflammation, and apoptosis.Curr Alzheimer Res.202410.2174/0115672050315334240508162754.
    [Google Scholar]
  15. BayomiH.S. ElsherbinyN.M. El-GayarA.M. Al-GayyarM.M.H. Evaluation of renal protective effects of inhibiting TGF-β type I receptor in a cisplatin-induced nephrotoxicity model.Eur. Cytokine Netw.201324413914710.1684/ecn.2014.034424590376
    [Google Scholar]
  16. AlbalawiG.A. AlbalawiM.Z. AlsubaieK.T. AlbalawiA.Z. ElewaM.A.F. HashemK.S. Al-GayyarM.M.H. Curative effects of crocin in ulcerative colitis via modulating apoptosis and inflammation.Int. Immunopharmacol.202311811013810.1016/j.intimp.2023.11013837030122
    [Google Scholar]
  17. ElsherbinyN.M. Al-GayyarM.M.H. Abd El GalilK.H. Nephroprotective role of dipyridamole in diabetic nephropathy: Effect on inflammation and apoptosis.Life Sci.201514381710.1016/j.lfs.2015.10.02626596562
    [Google Scholar]
  18. HassanH.M. HamdanA.M. AlattarA. AlshamanR. BahattabO. Al-GayyarM.M.H. Evaluating anticancer activity of emodin by enhancing antioxidant activities and affecting PKC/ADAMTS4 pathway in thioacetamide-induced hepatocellular carcinoma in rats.Redox Rep.2024291236559010.1080/13510002.2024.236559038861483
    [Google Scholar]
  19. AlattarA. AlshamanR. Al-GayyarM.M.H. Therapeutic effects of sulforaphane in ulcerative colitis: Effect on antioxidant activity, mitochondrial biogenesis and DNA polymerization.Redox Rep.202227112813810.1080/13510002.2022.209237835754320
    [Google Scholar]
  20. BagalagelA. DiriR. NoorA. AlmasriD. BakhshH.T. KutbiH.I. Al-GayyarM.M.H. Curative effects of fucoidan on acetic acid induced ulcerative colitis in rats via modulating aryl hydrocarbon receptor and phosphodiesterase-4.BMC Complement Med Ther202222119610.1186/s12906‑022‑03680‑435870906
    [Google Scholar]
  21. AlbalawiAZ. AlatawiAS. Al-AtwiSM. Echinacoside ameliorates hepatic fibrosis and tumor invasion in rats with thioacetamide-induced hepatocellular carcinoma.Biomol Biomed.202410.17305/bb.2024.10367
    [Google Scholar]
  22. AlharbiT.S. AlshammariZ.S. AlanziZ.N. AlthobaitiF. ElewaM.A.F. HashemK.S. Al-GayyarM.M.H. Therapeutic effects of genistein in experimentally induced ulcerative colitis in rats via affecting mitochondrial biogenesis.Mol. Cell. Biochem.2024479243144410.1007/s11010‑023‑04746‑837084167
    [Google Scholar]
  23. ZhangX.X. TianY. WangZ.T. MaY.H. TanL. YuJ.T. The epidemiology of alzheimer’s disease modifiable risk factors and prevention.J. Prev. Alzheimers Dis.20218331332134101789
    [Google Scholar]
  24. KandimallaR. VallamkonduJ. CorgiatE.B. GillK.D. Understanding aspects of aluminum exposure in Alzheimer’s disease development.Brain Pathol.201626213915410.1111/bpa.1233326494454
    [Google Scholar]
  25. YangJ. WiseL. FukuchiK. TLR4 cross-talk with NLRP3 inflammasome and complement signaling pathways in Alzheimer’s disease.Front. Immunol.20201172410.3389/fimmu.2020.0072432391019
    [Google Scholar]
  26. LiY. ChenX. ZhouM. FengS. PengX. WangY. Microglial TLR4/NLRP3 inflammasome signaling in alzheimer’s disease.J. Alzheimers Dis.2024971758810.3233/JAD‑23027338043010
    [Google Scholar]
  27. XuX. ZengX.Y. CuiY.X. LiY.B. ChengJ.H. ZhaoX.D. XuG.H. MaJ. PiaoH.N. JinX. PiaoL.X. Antidepressive effect of arctiin by attenuating neuroinflammation via HMGB1/TLR4- and TNF-α/TNFR1-mediated NF-κB activation.ACS Chem. Neurosci.202011152214223010.1021/acschemneuro.0c0012032609480
    [Google Scholar]
  28. LuJ.M. XuX. AosaiF. ZhangM.Y. ZhouL.L. PiaoL.X. Protective effect of arctiin against Toxoplasma gondii HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of cytosolic phospholipase A2 and platelet-activating factor.Int. Immunopharmacol.202412611125410.1016/j.intimp.2023.11125437995571
    [Google Scholar]
  29. AntarS.A. AshourN.A. MarawanM.E. Al-KarmalawyA.A. Fibrosis: Types, effects, markers, mechanisms for disease progression, and its relation with oxidative stress, immunity, and inflammation.Int. J. Mol. Sci.2023244400410.3390/ijms2404400436835428
    [Google Scholar]
  30. AlghamdiM.A. KhalifahT.A. AlhawatiH.S. RuzayqM. AlrakafA. KhodierA. Al-GayyarM.M. Antitumor activity of ferulic acid against ehrlich solid carcinoma in rats via Affecting Hypoxia, Oxidative Stress and Cell Proliferation.Cureus2023157e4198510.7759/cureus.4198537465088
    [Google Scholar]
  31. KasembeliM.M. BharadwajU. RobinsonP. TweardyD.J. Contribution of STAT3 to inflammatory and fibrotic diseases and prospects for its targeting for treatment.Int. J. Mol. Sci.2018198229910.3390/ijms1908229930081609
    [Google Scholar]
  32. ParkJ.K. LeeK.J. KimJ.Y. KimH. The association of blood-based inflammatory factors IL-1β, TGF-β and CRP with cognitive function in alzheimer’s disease and mild cognitive impairment.Psychiatry Investig.2021181111810.30773/pi.2020.020533561929
    [Google Scholar]
  33. LiuX. WangJ. DouP. ZhangX. RanX. LiuL. DouD. The ameliorative effects of arctiin and arctigenin on the oxidative injury of lung induced by silica via TLR-4/NLRP3/TGF-β signaling pathway.Oxid. Med. Cell. Longev.2021202111810.1155/2021/559898034336106
    [Google Scholar]
  34. LeeJ.H. KimC. LeeJ. UmJ.Y. SethiG. AhnK.S. Arctiin is a pharmacological inhibitor of STAT3 phosphorylation at tyrosine 705 residue and potentiates bortezomib-induced apoptotic and anti-angiogenic effects in human multiple myeloma cells.Phytomedicine20195528229210.1016/j.phymed.2018.06.03830668440
    [Google Scholar]
  35. HoozemansJ.J.M. BrücknerM.K. RozemullerA.J.M. VeerhuisR. EikelenboomP. ArendtT. Cyclin D1 and cyclin E are co-localized with cyclo-oxygenase 2 (COX-2) in pyramidal neurons in Alzheimer disease temporal cortex.J. Neuropathol. Exp. Neurol.200261867868810.1093/jnen/61.8.67812152783
    [Google Scholar]
  36. AlshehriA. AlbuhayriA. AlanaziM. AlthubaitiM.A. AljehaniR.F. AlsharifF.I. AlatawiT.M. AlbalawiS.S. KhodirA.E. Al-GayyarM.M. Effects of echinacoside on ehrlich carcinoma in rats by targeting proliferation, hypoxia and inflammation.Cureus20231510e4680010.7759/cureus.4680037822691
    [Google Scholar]
  37. VissersJ.H.A. FroldiF. SchröderJ. PapenfussA.T. ChengL.Y. HarveyK.F. The Scalloped and Nerfin-1 Transcription factors cooperate to maintain neuronal cell fate.Cell Rep.201825615611576.e710.1016/j.celrep.2018.10.03830404010
    [Google Scholar]
  38. BeckmannA. RamirezP. GamezM. GonzalezE. De MangeJ. BieniekK.F. RayW.J. FrostB. Moesin is an effector of tau-induced actin overstabilization, cell cycle activation, and neurotoxicity in Alzheimer’s disease.iScience202326310615210.1016/j.isci.2023.10615236879821
    [Google Scholar]
  39. LiuZ. WuY. Arctiin elevates osteogenic differentiation of MC3T3-E1 cells by modulating cyclin D1.Bioengineered2022134108661087410.1080/21655979.2022.206604735473505
    [Google Scholar]
  40. YaghoubiM Safety Assessment of Arctium lappa L. fruit extract in female wistar rats: acute and repeated oral toxicity studies.Res. j. pharmacogn.201962394810.22127/rjp.2019.84317.
    [Google Scholar]
  41. MalaníkM. FarkováV. KřížováJ. KresováA. ŠmejkalK. KašparovskýT. DadákováK. Comparison of Metabolic Profiles of Fruits of Arctium lappa, Arctium minus , and Arctium tomentosum.Plant Foods Hum. Nutr.202479249750210.1007/s11130‑024‑01175‑w38589624
    [Google Scholar]
/content/journals/car/10.2174/0115672050333388240801043509
Loading
/content/journals/car/10.2174/0115672050333388240801043509
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test