skip to main content

Effect of Myristica fragrans on PGC1α and Synaptophysin Expression in Male Wistar Rats Hippocampus

1Department of Biomedicine, Faculty of Medicine, Universitas Padjadjaran, Indonesia

2Undergraduate Program, Faculty of Medicine, Universitas Padjadjaran, Indonesia

3Department of Oral Biology, Faculty of Dentistry, Universitas Padjadjaran, Indonesia

Received: 30 Aug 2024; Accepted: 19 Apr 2024; Available online: 30 Apr 2024; Published: 30 Apr 2024.
Open Access Copyright (c) 2024 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Citation Format:
Abstract

Background: Nutmeg is an indigenous plant from Indonesia that has been used extensively in herbal treatment. Nutmeg seed extract (NuSE) contains the active compound macelignan, which exhibits pharmacological activities. A previous study stated that NuSE is PPARγ or peroxisome proliferator-activated receptor gamma agonist that potentially enhances synaptic signal modulation. PPARγ activation can activate PGC1α or peroxisome proliferator-activated receptor gamma coactivator-1 alpha as the primary regulator of mitochondrial biogenesis. Mitochondria are involved in synaptic transmission. Increased modulation of signals at synapses can increase neuroplasticity, potentially improving the brain's cognitive function, as seen by the amount of Synaptophysin in the synaptic vesicle membrane for evaluating synaptogenesis.

Objective: This research demonstrates how nutmeg seed extract (NuSE) affects PGC1α and synaptophysin expression compared with DHA or docosahexanoieac acid, which has been evidenced to promote neurite growth.

Methods: Twenty-four Wistar male rats aged eight weeks were divided into four groups (control, PGA group, NuSE group, and DHA group). The treatment group was administered for 12 weeks using a gavage. After that, the rats were sacrificed, and the hippocampus neurons were collected. The PGC1α and Synaptophysin mRNA expression was measured using semiquantitative reversed PCR, visualized with electrophoresis, and then quantified with ImageJ.

Results: This study showed that NuSE increased synaptophysin and PGC1α mRNA expressions compared to the control group with significance statistic (p=0.017, p<0,05) in synaptophysin expression but did not increase PGC1α expression significantly (p=0.364, p>0,05).

Conclusion: In conclusion, nutmeg seed extract (NuSE) impacts synaptogenesis in synaptophysin expression to modulate synaptic transmission.

Note: This article has supplementary file(s).

Fulltext View|Download |  Cover Letter
Letter to the Editor
Subject Cover Letter
Type Cover Letter
  Download (48KB)    Indexing metadata
Keywords: Hippocampus; PGC-1a; NuSE; synaptophysin

Article Metrics:

  1. Kliegman RM, St JW, Iii G, et al. Nelson Textbook of Pediatrics. 21st ed. Elsevier, 2020
  2. Young PA, Young PH, Tolbert DL. Basic Clinical Neuroscience. Third. Wolters Kluwer, 2015
  3. Splittgerber R. Snell’s Clinical Neuroanatomy. Eighth. Wolters Klewer, 2015
  4. Veronica F, Lubis L, Fitri LL, et al. A preliminary study of the effect of PPAR-γ agonist from Myristica fragrans houtt seed extract on the biogenesis of rat infant’s brain mitochondria and D1 dopamine receptor. Bali Medical Journal (Bali Med J) 2018; 7: 574–577
  5. Quintanilla RA, Utreras E, Cabezas-Opazo FA. Role of PPAR γ in the differentiation and function of neurons. PPAR Res; 2014. Epub ahead of print 2014. DOI: 10.1155/2014/768594
  6. Popov LD. Mitochondrial biogenesis: An update. J Cell Mol Med 2020; 24: 4892
  7. Cardanho-Ramos C, Morais VA. Mitochondrial Biogenesis in Neurons: How and Where. Int J Mol Sci; 22. Epub ahead of print 1 December 2021. DOI: 10.3390/IJMS222313059
  8. Echeverría F, Valenzuela R, Catalina Hernandez-Rodas M, et al. Docosahexaenoic acid (DHA), a fundamental fatty acid for the brain: New dietary sources. Prostaglandins Leukot Essent Fatty Acids 2017; 124: 1–10
  9. Periasamy G, Karim A, Gibrelibanos M, et al. Nutmeg (Myristica fragrans Houtt.) Oils. In: Essential Oils in Food Preservation, Flavor and Safety. Elsevier, 2015, pp. 607–616
  10. d’Angelo M, Castelli V, Catanesi M, et al. PPARγ and Cognitive Performance. Int J Mol Sci; 20. Epub ahead of print 2 October 2019. DOI: 10.3390/IJMS20205068
  11. Adams DJ, Arthur CP, Stowell MHB. Architecture of the Synaptophysin/Synaptobrevin Complex: Structural Evidence for an Entropic Clustering Function at the Synapse. Sci Rep; 5. Epub ahead of print 3 September 2015. DOI: 10.1038/SREP13659
  12. Veronica F, Fitri LL, Rizal Ganiem A, et al. Expression of Nutmeg Seed Extract in Integral Membrane Protein and Synaptic Vesicle: Younger Vs Aging. 2020
  13. Lestari K, Hwang J, Kariadi SH, et al. Screening For PPAR-γ Agonist From Myristica Fragrans Houtt Seeds for The Treatment Of Type 2 Diabetes By In Vitro And In Vivo. Medical and Health Science Journal 2012; 12: 7–15
  14. Paul S, Hwang JK, Kim HY, et al. Multiple biological properties of macelignan and its pharmacological implications. Archives of Pharmacal Research 2013; 36: 264–272
  15. Lesmana R, Siannoto M, Nugraha GI, et al. Nutmeg extract potentially alters characteristics of white adipose tissue in rats. Vet Med Sci 2021; 7: 512–520
  16. Nie F, Liang Y, Xun H, et al. Inhibitory effects of tannic acid in the early stage of 3T3-L1 preadipocytes differentiation by down-regulating PPARγ expression. Food Funct 2015; 6: 894–901
  17. Fujimaki T, Sato C, Yamamoto R, et al. Isolation of phenolic acids and tannin acids from Mangifera indica L. kernels as inhibitors of lipid accumulation in 3T3-L1 cells. Biosci Biotechnol Biochem 2022; 86: 665–671
  18. Tchantchou F, Lacor PN, Cao Z, et al. Stimulation of Neurogenesis and Synaptogenesis by Bilobalide and Quercetin via Common Final Pathway in Hippocampal Neurons. Journal of Alzheimer’s Disease 2009; 18: 787–798
  19. Ortuño Sahagún D, Márquez-Aguirre AL, Quintero-Fabián S, et al. Modulation of PPAR-γ by nutraceutics as complementary treatment for obesity-related disorders and inflammatory diseases. PPAR Res. Epub ahead of print 2012. DOI: 10.1155/2012/318613
  20. Han KL, Choi JS, Lee JY, et al. Therapeutic Potential of Peroxisome Proliferators–Activated Receptor-α/γ Dual Agonist With Alleviation of Endoplasmic Reticulum Stress for the Treatment of Diabetes. Diabetes 2008; 57: 737–745
  21. Jissa G, Sai-Sailesh, Mukkadan. Oral Administration of Nutmeg on Memory Boosting and Regaining in Wistar Albino Rats. Bali Medical Journal (BMJ) 2014; 3: 7–10
  22. Kwon SE, Chapman ER. Synaptophysin regulates the kinetics of synaptic vesicle endocytosis in central neurons. Neuron 2011; 70: 847
  23. Harrill JA, Chen H, Streifel KM, et al. Ontogeny of biochemical, morphological and functional parameters of synaptogenesis in primary cultures of rat hippocampal and cortical neurons. Mol Brain 2015; 8: 1–15
  24. Hashimoto M, Hossain S, Al Mamun A, et al. Docosahexaenoic acid: one molecule diverse functions. Crit Rev Biotechnol 2017; 37: 579–597
  25. Cichon N, Saluk-Bijak J, Gorniak L, et al. Flavonoids as a Natural Enhancer of Neuroplasticity—An Overview of the Mechanism of Neurorestorative Action. Antioxidants 2020, Vol 9, Page 1035 2020; 9: 1035
  26. Le TVT, Nguyen PH, Choi HS, et al. Diarylbutane-type lignans from Myristica fragrans (Nutmeg) show the cytotoxicity against breast cancer cells through activation of AMP-activated protein kinase. Natural Product Sciences 2017; 23: 21–28
  27. Gray NE, Zweig JA, Caruso M, et al. Centella asiatica increases hippocampal synaptic density and improves memory and executive function in aged mice. Brain Behav 2018; 8: 1024
  28. Shukla VK, Lad VD. Short Review: Nrf2 and Omega 3 for Human Health. Epub ahead of print 2022. DOI: 10.33552/ICBC.2022.02.000534
  29. Zhao WN, Hylton NK, Wang J, et al. Activation of WNT and CREB signaling pathways in human neuronal cells in response to the Omega-3 fatty acid docosahexaenoic acid (DHA). Molecular and Cellular Neuroscience; 99. Epub ahead of print 1 September 2019. DOI: 10.1016/j.mcn.2019.06.006

Last update:

No citation recorded.

Last update:

No citation recorded.