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Cited by 9Alzheimer's disease research and treatmentsMedicinal Plants and NeuroprotectionBioactive natural compounds

Dual Role of Phenyl Amides from Hempseed on BACE 1, PPARγ, and PGC-1α in N2a-APP Cells

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Rea Martinez, Julio, Šelo, Gordana, Fernández-Arche, María Ángeles, Bermudez, Beatriz, García-Giménez, María Dolores·2021·Journal of Natural Products
DOI 10.1021/acs.jnatprod.1c00435PMC PMC8610369
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Abstract

High Resolution Image Download MS PowerPoint Slide In Alzheimer’s disease (AD) the accumulation of amyloid β (Aβ) plaques in the brain leads to neuroinflammation, neuronal cell dysfunction, and progressive memory loss. Therefore, blocking the formation of Aβ plaques has emerged as one of the most promising strategies to develop AD treatments. Hempseed is widely used as a food, and recently its compounds have shown beneficial effects on neuroinflammation. The objective of this study was to investigate whether a fraction rich in phenyl amide compounds, N - trans -caffeoyltyramine (CAFT) and N - trans -coumaroyltyramine (CUMT), can affect gene expression: β-site amyloid-precursor-protein-cleaving enzyme 1 (BACE 1), peroxisome proliferator-activated receptor gamma (PPAR γ), and PPARγ-coactivator-1α (PGC-1α) in N2a-APP cells. The mRNA levels were measured using RT-qPCR. The ethyl acetate fraction and CAFT were found to reduce BACE1 gene expression and are promissory PPARγ and PGC-1α natural agonists. The results show that hempseed compounds can inhibit the expression of BACE 1, which is involved in the accumulation of Aβ plaques and positively affect transcription factors involved in complex and diverse biological functions.

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  • 0.03 and 0.08 μM N-trans-caffeoyltyramine upregulated PGC-1α expression by approximately twofold after 24 h, with slight diminution after 48 h.

    “A total of 0.03 and 0.08 μM of N-trans-caffeoyltyramine had comparable effects on PGC-1α expression, upregulating by approximately twofold after 24 h, again with a slight diminution after 48 h of exposure.”

    From Exploring the Lesser-Known Bioactive Natural Products of Plant Species of the Genus Cannabis L.: Alkaloids, Phenolic Compounds, and Their Therapeutic Potential (2025) · cites this paper as [73]

    The Results and Discussion text and Figure 6 caption report increased PGC-1α expression in N2a-APP cells treated with caffeoyltyramine at 0.03–0.08 μM for 24 hours, with expression still elevated after 48 hours. Our copy does not give an approximately twofold increase, establish that the two doses had comparable effects, or clearly quantify a slight diminution at 48 hours. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • N-trans-caffeoyltyramine very significantly reduced BACE1 expression in N2a cells at 0.03 μM, more at 24 h than at 48 h.

    “N-trans-caffeoyltyramine very significantly reduced the BACE 1 expression of N2a cells at 0.03 μM, more so at 24 h of exposure than 48 h [73].”

    From Exploring the Lesser-Known Bioactive Natural Products of Plant Species of the Genus Cannabis L.: Alkaloids, Phenolic Compounds, and Their Therapeutic Potential (2025) · cites this paper as [73]

    The Results and Discussion text and Figure 4 caption (page not available in our copy) report significant BACE 1 gene-expression reduction with N-trans-caffeoyltyramine at the tested concentrations, which include 0.03 μM, in N2a-APP cells. They describe its suppression as remaining active or stable at 48 h; they do not establish that the reduction was greater at 24 h than at 48 h. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • PGC-1α is a coactivator participating in PPARγ transcription, and decreased expression is thought to be linked to Alzheimer's disease.

    “PGC-1α is a coactivator participating in PPARγ transcription and decreased expression is thought to be linked to Alzheimer’s disease [73].”

    From Exploring the Lesser-Known Bioactive Natural Products of Plant Species of the Genus Cannabis L.: Alkaloids, Phenolic Compounds, and Their Therapeutic Potential (2025) · cites this paper as [73]

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Research works printed but not linked: 32

  1. Cao G.; Su P.; Zhang S.; Guo L.; Zhang H.; Liang Y.; et al. Eur. J. Pharmacol. 2016, 793, 101– 8. 10.1016/j.ejphar.2016.11.006. 27840193 · DOI
  2. Kolaj I.; Liyanage S.; Weaver D. F. Neurochem. Int. 2018, 120, 99– 111. 10.1016/j.neuint.2018.08.001. 30098379 · DOI
  3. Katsouri L.; Lim Y. M.; Blondrath K.; Eleftheriadou I.; Lombardero L.; Birch A. M.; et al. Proc. Natl. Acad. Sci. U. S. A. 2016, 113, 12292– 7. 10.1073/pnas.1606171113. 27791018 PMC5087021 · DOI · Paper page
  4. Cox C. J.; Choudhry F.; Peacey E.; Perkinton M. S.; Richardson J. C.; Howlett D. R.; et al. Neurobiol. Aging 2015, 36, 178– 87. 10.1016/j.neurobiolaging.2014.07.032. 25316600 PMC4270442 · DOI
  5. Wang Z.; Huang X.; Zhao P.; Zhao L.; Wang Z. Y. Front. Aging Neurosci. 2018, 10, 1– 11. 10.3389/fnagi.2018.00066. 29615891 PMC5867310 · DOI
  6. Rowinska-Zyrek M.; Salerno M.; Kozlowski H. Coord. Chem. Rev. 2015, 284, 298– 312. 10.1016/j.ccr.2014.03.026. · DOI
  7. Könczöl A.; Müller J.; Földes E.; Béni Z.; Végh K.; Kéry A.; et al. J. Nat. Prod. 2013, 76, 655– 63. 10.1021/np300882f. 23565574 · DOI · Paper page
  8. Callaway J. C. Euphytica 2004, 140, 65– 72. 10.1007/s10681-004-4811-6. · DOI · Paper page
  9. Montserrat-De La Paz S.; Marín-Aguilar F.; García-Giménez M. D.; Fernández-Arche M. A. J. Agric. Food Chem. 2014, 62, 1105– 10. 10.1021/jf404278q. 24422510 · DOI
  10. Zhou Y.; Wang S.; Lou H.; Fan P. Phytochem. Lett. 2018, 23, 57– 61. 10.1016/j.phytol.2017.11.013. · DOI
  11. Luo Q.; Yan X.; Bobrovskaya L.; Ji M.; Yuan H.; Lou H.; et al. Mol. Cell. Biochem. 2017, 428, 129– 37. 10.1007/s11010-016-2923-7. 28224333 · DOI · Paper page
  12. Zhou Y.; Wang S.; Ji J.; Lou H.; Fan P. ACS Omega. 2018, 3, 15988– 95. 10.1021/acsomega.8b02250. 30556022 PMC6288804 · DOI
  13. Selkoe D. J.; Hardy J. EMBO Mol. Med. 2016, 8, 595– 608. 10.15252/emmm.201606210. 27025652 PMC4888851 · DOI · Paper page
  14. Cai W.; Yang T.; Liu H.; Han L.; Zhang K.; Xiaoming H.; et al. Prog. Neurobiol. 2018, 163–164, 27– 58. 10.1016/j.pneurobio.2017.10.002. PMC6037317 29032144 · DOI
  15. Bucic-Kojic A.; Selo G.; Zeli B.; Planini M.; Tisma M. Appl. Biochem. Biotechnol. 2017, 181, 948– 60. 10.1007/s12010-016-2261-y. 27696141 · DOI
  16. Rea Martinez J.; Montserrat de la Paz S.; De la Puerta R.; García-Giménez M.; Fernández-Arche M. Food Funct. 2020, 11, 4057– 66. 10.1039/D0FO00066C. 32329481 · DOI
  17. Rea J.; García-Giménez M.; Santiago M.; De la Puerta R.; Fernández-Arche M. Int. J. Food Sci. Nutr. 2021, 72, 184– 94. 10.1080/09637486.2020.1793305. 32664762 · DOI
  18. Nigro E.; Crescente G.; Formato M.; Pecoraro M. T.; Mallardo M.; Piccolella S.; et al. Molecules 2020, 25, 1049 10.3390/molecules25051049. PMC7179246 32110947 · DOI
  19. Crescente G.; Piccolella S.; Esposito A.; Scognamiglio M.; Fiorentino A.; Pacifico S. Phytochem. Rev. 2018, 17, 733– 49. 10.1007/s11101-018-9556-2. · DOI
  20. Könczöl A.; Rendes K.; Dékány M.; Müller J.; Riethmüller E.; Balogh G. T. J. Pharm. Biomed. Anal. 2016, 131, 167– 74. 10.1016/j.jpba.2016.08.032. 27592255 · DOI
  21. Teh S. S.; Birch E. J. Ultrason. Sonochem. 2014, 21, 346– 53. 10.1016/j.ultsonch.2013.08.002. 23993457 · DOI
  22. Zhang Z. X.; Li Y. B.; Zhao R. P. Neurochem. Res. 2017, 42, 468– 80. 10.1007/s11064-016-2093-8. 27889855 · DOI
  23. Hampel H.; Vassar R.; De Strooper B.; Hardy J.; Willem M.; Singh N.; Biol. Psychiatry 2021, 89, 745 10.1016/j.biopsych.2020.02.001. 32223911 PMC7533042 · DOI · Paper page
  24. Hu J.; Lin T.; Gao Y.; Xu J.; Jiang C.; Wang G.; et al. PLoS One. 2015, 10, 1– 13. PMC4309453 25629409
  25. Prati F.; Bottegoni G.; Bolognesi M. L.; Cavalli A. J. Med. Chem. 2018, 61, 619– 37. 10.1021/acs.jmedchem.7b00393. 28749667 · DOI
  26. Bakrudeen A.; Vidhyavathi R.; Magesh J.; Vijayakumar M.; Mustafa M. M.; Marikar F.M.MT. Annu. Res. Rev. Biol. 2018, 28, 1– 18. 10.9734/ARRB/2018/40571. · DOI
  27. Katsouri L.; Parr C.; Bogdanovic N.; Willem M.; Sastre M. J. Alzheimer's Dis. 2011, 25, 151– 62. 10.3233/JAD-2011-101356. 21358044 · DOI
  28. Sastre M.; Dewachter I.; Rossner S.; Bogdanovic N.; Rosen E.; Borghgraef P.; et al. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 443– 8. 10.1073/pnas.0503839103. 16407166 PMC1326151 · DOI · Paper page
  29. Austin S.; St-Pierre J. J. Cell Sci. 2012, 125, 4963– 71. 10.1242/jcs.113662. 23277535 · DOI
  30. Errico I. D.; Salvatore L.; Murzilli S.; Lo Sasso G.; Latorre D.; Martelli N.; et al. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 6603– 6608. 10.1073/pnas.1016354108. 21467224 PMC3081029 · DOI
  31. Qin W.; Haroutunian V.; Katsel P.; Cardozo C.; Ho L.; Buxbaum J.; et al. Arch Neurol. 2011, 66, 352– 361. PMC3052997 19273754
  32. Di L.; Kerns E. H.; Fan K.; McConnell O. J.; Carter G. T. Eur. J. Med. Chem. 2003, 38, 223– 232. 10.1016/S0223-5234(03)00012-6. 12667689 · DOI · Paper page

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Sorted by citations

Authors
Rea Martinez, J., Šelo, G., Fernández-Arche, M. Á., Bermudez, B., & García-Giménez, M. D.
Affiliations
  • Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, Spain
  • University of Osijek (HR)
  • Department of Cellular Biology, Faculty of Biology, University of Seville, 41012 Sevilla, Spain
ORCID
Venue
Journal of Natural Products
Publisher
American Chemical Society (ACS)
Published
2021-08-30
Volume
84
Issue
9
Pages
2447-2453
ISSN
  • 0163-3864 (ISSN-L)
  • 1520-6025
DOI
10.1021/acs.jnatprod.1c00435
PMC
PMC8610369
OpenAlex
W3197272374
Cited by
9
References
1
Citations by year
2025: 2 · 2024: 4 · 2023: 1 · 2022: 2
FWCI
1.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Natural Products (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Deposito de Investigacion Universidad de Sevilla (University of Seville) (submittedVersion, cc-by-nc-nd)
Funders
V Own Research Plan, University of Seville
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioactive natural compounds
Keywords
hemp seeds, BACE1, PPARγ, PGC-1α, Alzheimer's disease, amyloid plaques, neuroinflammation, gene expression regulation
MeSH terms
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Alzheimer Disease, Amides, Animals, Cannabis, Cell Line, Seeds, Spain, Tyramine, Molecular Structure, Gene Expression, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, PPAR gamma, Mice, Amyloid Precursor Protein Secretases, Phytochemicals

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