Skip to main content
SpringerLink
Log in

Neuroprotective Effects of Bromelain on the Common Neurodegenerative Diseases: A Systematic Review

  • REVIEW ARTICLES
  • Published:
Neurochemical Journal Aims and scope Submit manuscript

Abstract

In recent years, neurodegenerative diseases (NDs) have increased around the world and current treatments only provide temporary relief of the symptoms. So, we aimed to investigate the neuroprotective effects and possible mechanisms of bromelain on the main NDs such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Multiple sclerosis (MS). In this systematic review, we followed the PRISMA checklist 2020 guidelines. Embase, PubMed, Web of Science, Scopus, and Cochrane Library were searched for related articles published before August 1, 2023, using the combination of keywords that were derived based on MeSH terms and similar systematic review studies. The required information was extracted from the publications and recorded in Excel form, and the outcome and mechanisms were reviewed. Finally, 17 studies were selected for the investigation. Bromelain alleviates neuroinflammation by downregulating pro-inflammatory cytokines in the central nervous system. Bromelain also neutralizes free radicals and up-regulated levels of endogenous antioxidant enzymes and improves mitochondrial function in neural cells. So, by antioxidant and anti-inflammatory activity, bromelain neutralizes apoptosis and neuronal damage. Moreover, the immune response in the CNS may be regulated by bromelain. apoptosis and neuronal damage. This proteolytic enzyme also reduced β-amyloid aggregation in AD. In vivo, in vitro, and ex vivo studies revealed that bromelain shows promising neuroprotective effects on NDs by reducing inflammatory factors, and oxidative stress, regulating the immune system, and reducing neurotoxicity. However, more clinical trial studies are needed in this field.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

REFERENCES

  1. Dugger, B.N., and Dickson, D.W., Cold. Spring. Harb. Perspect. Biol., 2017, vol. 9, p. a028035.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Erkkinen, M.G., Kim, M.O., and Geschwind, M.D., Cold. Spring. Harb. Perspect. Biol., 2018, vol. 10, p. a033118.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lamptey, R.N.L., Chaulagain, B., Trivedi, R., Gothwal, A., Layek, B., and Singh, J., Int. J. Mol. Sci., 2022, vol. 23, p. 1851.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Reich, D.S., Lucchinetti, C.F., and Calabresi, P.A., N. Engl. J. Med., 2018, vol. 378, pp. 169–180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Christidi, F., Migliaccio, R., Santamaría-García, H., Santangelo, G., and Trojsi, F., Behav. Neurol., 2018, vol. 2018, p. 1849794.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Felekoğlu, E., Özalevli, S., Yakut, H., Aktan, R., and Yener, G., Medicina (Kaunas), 2021, vol. 57, p. 1067.

    Article  PubMed  Google Scholar 

  7. Aza, A., Gómez-Vela, M., Badia, M., Begoña Orgaz, M., González-Ortega, E., Vicario-Molina, I., and Montes-López, E., Health. Qual. Life. Outcomes., 2022, vol. 20, p. 76.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Mathur, S., Gawas, C., Ahmad, I.Z., Wani, M., and Tabassum, H., Aging. Med., 2023, vol. 6, pp. 82–97.

    Article  Google Scholar 

  9. Chen, W., Hu, Y., and Ju, D., Acta. Pharm. Sin. B, 2020, vol. 10, pp. 1347–1359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Di Paolo, M., Papi, L., Gori, F., and Turillazzi, E., Int. J. Mol. Sci., 2019, vol. 20, p. 5170.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mohamad, N.E., Abu, N., Yeap, S.K., and Alithe-en, N.B., Integr. Cancer. Ther., 2019, vol. 18, p. 1534735419880258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Park, S., Oh, J., Kim, M., and Jin, E.J., Anim. Cells Syst. (Seoul), 2018, vol. 22, pp. 334–340.

    Article  CAS  PubMed  Google Scholar 

  13. Chang, T.C., Wei, P.L., Makondi, P.T., Chen, W.T., Huang, C.Y., and Chang, Y.J., PLoS One, 2019, vol. 14, p. e0210274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Amini, A., Masoumi-Moghaddam, S., Ehteda, A., and Morris, D.L., J. Exp. Clin. Cancer Res., 2014, vol. 33, p. 92.

    PubMed  PubMed Central  Google Scholar 

  15. Agrawal, P., Nikhade, P., Patel, A., Mankar, N., and Sedani, S., Cureus, 2022, vol. 14, p. e27876.

    PubMed  PubMed Central  Google Scholar 

  16. Chakraborty, A.J., Mitra, S., Tallei, T.E., Tareq, A.M., Nainu, F., Cicia, D., Dhama, K., Emran, T.B., Simal-Gandara, J., and Capasso, R., Life (Basel), 2021, vol. 11, p. 317.

    PubMed  ADS  Google Scholar 

  17. Bakare, A.O. and Owoyele, B.V., Sci. Rep., 2021, vol. 11, p. 289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Asgari Savadjani, S., Yadollahi, F., and Khaghani, A., J. Shahrekord. Univ. Med. Sci., 2023, vol. 25, pp. 149–155.

    Article  Google Scholar 

  19. Varilla, C., Marcone, M., Paiva, L., and Baptista, J., Foods, 2021, vol. 10, p. 2249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mialovyts’ka, O.A., Lik. Sprava, 2003, vol. 3–4, pp. 109–113.

    Google Scholar 

  21. Çiçek, B., Gul, M., Taghizadehghalehjoughi, A., Okkay, U., Yildirim, S., Okkay, I.F., Ertugrul, M.S., et al., Eur. Neuropsychopharmacol., 2020, vol. 40, pp. S438–S439.

    Article  Google Scholar 

  22. Chaudhary, B. and Bist, R., Cell. Stress. Chaperones, 2017, vol. 22, pp. 371–376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Vojdani, A., Lerner, A., and Vojdani, E., Cells, 2021, vol. 10, p. 1111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Targoni, O.S., Tary-Lehmann, M., and Lehmann, P.V., J. Autoimmun., 1999, vol. 12, pp. 191–198.

    Article  CAS  PubMed  Google Scholar 

  25. Kristofiková, Z., Tejkalová, H., and Klaschka, J., Neurochem. Res., 2001, vol. 26, pp. 203–212.

    Article  PubMed  Google Scholar 

  26. Lauer, D., Reichenbach, A., and Birkenmeier, G., Exp. Neurol., 2001, vol. 167, pp. 385–392.

    Article  CAS  PubMed  Google Scholar 

  27. Paź, A., Zaborski, J., Kruszewska-Ozimowska, J., Członkowski, A., and Członkowska, A., Int. J. Immunother., 2002, vol. 18, pp. 13–19.

    Google Scholar 

  28. Baumhackl, U., Kappos, L., Radue, E.W., Freitag, P., Guseo, A., Daumer, M., and Mertin, J., Mult. Scler., 2005, vol. 11, pp. 166–168.

    Article  CAS  PubMed  Google Scholar 

  29. Hou, R.C., Chen, Y.S., Huang, J.R., and Jeng, K.C., J. Agric. Food Chem., 2006, vol. 54, pp. 2193–2198.

    Article  CAS  PubMed  Google Scholar 

  30. Abbasi Habashi, S., Sabouni, F., Moghimi, A., Ansari Majd, S., and Tafreshi, A.P., J. Cell. Mol. Med., 2011, vol. 3, pp. 57–65.

    Google Scholar 

  31. Abbasi Habashi, S., Sabouni, F., Moghimi, A., and Ansari Majd, S., Iran. Biomed. J., 2016, vol. 20, pp. 33–40.

    PubMed  PubMed Central  Google Scholar 

  32. Sancesario, G.M., Nuccetelli, M., Cerri, A., Zegeer, J., Severini, C., Ciotti, M.T., Pieri, M., et al., Curr. Alzheimer. Res., 2018, vol. 15, pp. 628–636.

    Article  CAS  PubMed  Google Scholar 

  33. Mukherjee, D., Bhattacharjee, P., Bhattacharya, R., Dutta, A.K., and Bhattacharyya, D., Curr. Sci., 2018, vol. 115, pp. 2133–2141.

    Article  CAS  Google Scholar 

  34. Adu, T.S., and Mabandla, M.V., Metab. Brain. Dis., 2019, vol. 34, pp. 1557–1564.

    Article  CAS  PubMed  Google Scholar 

  35. Adu, T.S. and Mabandla, M.V.M., J. Neurol. Neurophysiol., 2020, vol. 11, p. 508.

    Google Scholar 

  36. Sromona, D., Sangita, D., Ramesh, K.P., Subhas, C.B., Umesh, C.H., and Debasish, B., bioRxiv, 2020, p. 2020.2004.2020.051193.

  37. Adu, T.S. and Mabandla, M.V., Brain Disorders, 2021, vol. 3, p. 100018.

    Article  CAS  Google Scholar 

  38. Ferah Okkay, I., Okkay, U., Cicek, B., Yilmaz, A., Yesilyurt, F., Mendil, A.S., and Hacimuftuoglu, A., Mol. Biol. Rep., 2021, vol. 48, pp. 7711–7717.

    Article  CAS  PubMed  Google Scholar 

  39. Kumar, R., Kumar, R., Sharma, N., Khurana, N., Singh, S.K., Satija, S., Mehta, M., and Vyas, M., Neurotoxicology, 2022, vol. 90, pp. 19–34.

    Article  CAS  PubMed  Google Scholar 

  40. Eraky, S.M., Ramadan, N.M., and Abo El-Magd, N.F., Int. J. Biol. Macromol., 2023, vol. 227, pp. 1119–1131.

    Article  CAS  PubMed  Google Scholar 

  41. Pezzani, R., Jiménez-Garcia, M., Capó, X., Sönmez Gürer, E., Sharopov, F., Rachel, T.Y.L., Ntieche Woutouoba, D., et al., Front. Oncol., 2022, vol. 12, p. 1068778.

    Article  CAS  PubMed  Google Scholar 

  42. Dyall, S.C., Int. J. Alzheimers. Dis., 2010, vol. 2010, p. 274128.

    PubMed Central  Google Scholar 

  43. Kwon, H.S., and Koh, S.-H., Transl. Neurodegener., 2020, vol. 9, p. 42.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Insuan, O., Janchai, P., Thongchuai, B., Chaiwongsa, R., Khamchun, S., Saoin, S., Insuan, W., et al., Curr. Issues. Mol. Biol., 2021, vol. 43, pp. 93–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Engwerda, C.R., Andrew, D., Ladhams, A., and Mynott, T.L., Cell Immunol., 2001, vol. 210, pp. 66–75.

    Article  CAS  PubMed  Google Scholar 

  46. Garland, E.F., Hartnell, I.J., and Boche, D., Front. Neurosci., 2022, vol. 16, p. 824888.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Wang, W.Y., Tan, M.S., Yu, J.T., and Tan, L., Ann. Transl. Med., 2015, vol. 3, p. 136.

    PubMed  PubMed Central  Google Scholar 

  48. Scheff, S.W., and Ansari, M.A., J. Neurotrauma, 2017, vol. 34, pp. 1491–1510.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ronaldson, P.T., and Davis, T.P., J. Cereb. Blood. Flow. Metab., 2020, vol. 40, pp. S6–S24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Salimi, H. and Klein, R.S., Neuroimmune Dis., 2019, pp. 195–234.

  51. Solleiro-Villavicencio, H. and Rivas-Arancibia, S., Front. Cell. Neurosci., 2018, vol. 12, p. 114.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Stefanis, L., Cold. Spring. Harb. Perspect. Med., 2012, vol. 2, p. a009399.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Gao, H.M., Zhang, F., Zhou, H., Kam, W., Wilson, B., and Hong, J.S., Environ. Health. Perspect., 2011, vol. 119, pp. 807–814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang, W., Wang, T., Pei, Z., Miller, D.S., Wu, X., Block, M.L., Wilson, B., et al., Faseb. J., 2005, vol. 19, pp. 533–542.

    Article  CAS  PubMed  Google Scholar 

  55. Klegeris, A., Pelech, S., Giasson, B.I., Maguire, J., Zhang, H., McGeer, E.G., and McGeer, P.L., Neurobiol. Aging, 2008, vol. 29, pp. 739–752.

    Article  CAS  PubMed  Google Scholar 

  56. Gao, H.M., Kotzbauer, P.T., Uryu, K., Leight, S., Trojanowski, J.Q., and Lee, V.M., J. Neurosci., 2008, vol. 28, pp. 7687–7698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Lyra, P., Machado, V., Rota, S., Chaudhuri, K.R., Botelho, J., and Mendes, J.J., Int. J. Mol. Sci., 2023, vol. 24, p. 7137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Rukmangadachar, L.A. and Bollu, P.C. Amyloid Beta Peptide [Updated 2022 Aug 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459119/.

    Google Scholar 

  59. Ismail, R., Parbo, P., Madsen, L.S., Hansen, A.K., Hansen, K.V., Schaldemose, J.L., Kjeldsen, P.L., et al., J. Neuroinflammation, 2020, vol. 17, p. 151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lukiw, W.J., Expert. Opin. Emerg. Drugs, 2012, vol. 23.https://doi.org/10.1517/14728214.2012.672559

  61. Uttara, B., Singh, A.V., Zamboni, P., and Mahajan, R.T., Curr. Neuropharmacol., 2009, vol. 7, pp. 65–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bakare, A.O., and Owoyele, B.V., Korean J. Pain, 2020, vol. 33, pp. 13–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. El-Demerdash, F.M., Hussien, D.M., Ghanem, N.F., and Al-Farga, A.M., Biomed. Res. Int., 2022, vol. 2022, p. 5342559.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Basu, P., Averitt, D.L., Maier, C., and Basu, A., Antioxidants (Basel), 2022, vol. 11, p. 430.

    Article  CAS  PubMed  Google Scholar 

  65. Angelova, P.R., Horrocks, M.H., Klenerman, D., Gandhi, S., Abramov, A.Y., and Shchepinov, M.S., J. Neurochem., 2015, vol. 133, pp. 582–589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Angelova, P.R. and Abramov, A.Y., FEBS Lett., 2018, vol. 592, pp. 692–702.

    Article  CAS  PubMed  Google Scholar 

  67. Reddy, P.H., Kshirsagar, S., Bose, C., Pradeepkiran, J.A., Hindle, A., Singh, S.P., and Reddy, A.P., Biochim. Biophys. Acta. Mol. Basis. Dis., 2023, vol. 1869, p. 166759.

    Article  CAS  Google Scholar 

  68. Misrani, A., Tabassum, S., and Yang, L., Front. Aging Neurosci., 2021, vol. 13, pp. 1–20.

    Google Scholar 

  69. Murphy, M.P. and Hartley, R.C., Nat. Rev. Drug. Discov., 2018, vol. 17, pp. 865–886.

    Article  CAS  PubMed  Google Scholar 

  70. Liu, F., Nguyen, J.L., Hulleman, J.D., Li, L., and Rochet, J.C., J. Neurochem., 2008, vol. 105, pp. 2435–2453.

    Article  CAS  PubMed  Google Scholar 

  71. Bist, R., Chaudhary, B., and Bhatt, D.K., Sci. Rep., 2021, vol. 11, p. 3668.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  72. Walters, M.E., Esfandi, R., and Tsopmo, A., Foods, 2018, vol. 7, p. 172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Fan, C., Ge, X., Hao, J., Wu, T., Liu, R., Sui, W., Geng, J., and Zhang, M., Food. Chemistry., 2023, vol. 399, p. 133912.

    Article  CAS  PubMed  Google Scholar 

  74. Wang, Y., Cai, M., Zeng, H., Zhao, H., Zhang, M., and Yang, Z., Int. J. Pept. Res. Ther., 2022, vol. 28, p. 116.

    Article  CAS  Google Scholar 

  75. Rajan, P.K., Dunna, N.R., and Venkatabalasubramanian, S., Expert. Opin. Biol. Ther., 2022, vol. 22, pp. 615–625.

    Article  CAS  PubMed  Google Scholar 

  76. Agarwal, S., Chaudhary, B., and Bist, R., Chem. Biol. Interact., 2016, vol. 254, pp. 173–178.

    Article  CAS  PubMed  Google Scholar 

  77. Agarwal, S., Chaudhary, B., Bist, R., Chem. Biol. Interact., 2017, vol. 261, pp. 139–144.

    Article  CAS  PubMed  Google Scholar 

  78. Nisar, A., Jagtap, S., Vyavahare, S., Deshpande, M., Harsulkar, A., Ranjekar, P., and Prakash, O., Front. Pharmacol., 2023, vol. 14, p. 1177050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Witt, S.N., and Flower, T.R., FEMS Yeast Res., 2006, vol. 6, pp. 1107–1116.

    Article  CAS  PubMed  Google Scholar 

  80. Pauzi, A.Z., Yeap, S.K., Abu, N., Lim, K.L., Omar, A.R., Aziz, S.A., Chow, A.L., Subramani, T., Tan, S.G., and Alitheen, N.B., Chin. Med., 2016, vol. 11, p. 46.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Hammond, T.R., Marsh, S.E., and Stevens, B., Immunity, 2019, vol. 50, pp. 955–974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Rathnavelu, V., Alitheen, N.B., Sohila, S., Kanagesan, S., and Ramesh, R., Biomed. Rep., 2016, vol. 5, pp. 283–288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Pothacharoen, P., Chaiwongsa, R., Chanmee, T., Insuan, O., Wongwichai, T., Janchai, P., and Vaithanomsat, P., Plants, 2021, vol. 10, p. 2273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Braidy, N. and Liu, Y., Exp. Gerontol., 2020, vol. 132, p. 110831.

    Article  CAS  PubMed  Google Scholar 

  85. Cheignon, C., Tomas, M., Bonnefont-Rousselot, D., Faller, P., Hureau, C., and Collin, F., Redox. Biol., 2018, vol. 14, pp. 450–464.

    Article  CAS  PubMed  Google Scholar 

  86. Abramov, A.Y., Potapova, E.V., Dremin, V.V., and Dunaev, A.V., Life (Basel), 2020, vol. 10, p. 101.

    CAS  PubMed  ADS  Google Scholar 

  87. Candreva, J., Chau, E., Rice, M.E., and Kim, J.R., Biochemistry, 2020, vol. 59, pp. 425–435.

    Article  CAS  PubMed  Google Scholar 

  88. Haque, M.M., Murale, D.P., Kim, Y.K., and Lee, J.S., Int. J. Mol. Sci., 2019, vol. 20, p. 1959.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Esteras, N., Kundel, F., Amodeo, G.F., Pavlov, E.V., Klenerman, D., and Abramov, A.Y., FEBS J., 2021, vol. 288, pp. 127–141.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

No external funding was received.

Author information

Authors and Affiliations

  1. Harvard Medical School, Department of Medicine, Boston, USA

    Sahar Rostamian

  2. Medical Physics School of Allied Medical Sciences Clinical Biochemistry Research Basic Health Sciences Institute Shahrekord University of Medical Sciences, Shahrekord, Iran

    Elham Raeisi

  3. Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

    Saeid Heidari-Soureshjani

  4. Pediatric Clinical Pharmacology and Toxicology, Department of Pediatrics, Wright State University Boonshoft School of Medicine, Dayton Children’s Hospital, One Children’s Plaza, Dayton, Ohio, USA

    Catherine M. T. Sherwin

Authors
  1. Sahar Rostamian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elham Raeisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saeid Heidari-Soureshjani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Catherine M. T. Sherwin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Sahar Rostamian, Elham Raeisi, and Saeid Heidari-Soureshjani. The first draft of the manuscript was written by Catherine M.T. Sherwin and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Elham Raeisi.

Ethics declarations

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This work does not contain any studies involving human and animal subjects.

CONFLICT OF INTEREST

The authors of this work declare that they have no conflicts of interest.

Additional information

Publisher’s Note.

Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Corresponding author; address: Shahrekord University of Medical Sciences, Department of Medicine, phone: +989133811217, Fax: +98383351031; e-mail: elhamraeisi@gmail.com.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sahar Rostamian, Raeisi, E., Heidari-Soureshjani, S. et al. Neuroprotective Effects of Bromelain on the Common Neurodegenerative Diseases: A Systematic Review. Neurochem. J. 17, 715–726 (2023). https://doi.org/10.1134/S1819712423040256

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1819712423040256

Keywords:

Search

Navigation