Carotenoid pigment from Micrococcus luteus confers neuroprotection in a cellular model of Parkinson’s disease via BDNF upregulation and oxidative stress reduction

Authors

  • Aiswarya Krishnan Department of Microbiology, Center for Research on Molecular Biology and Applied Science, Thiruvananthapuram, Kerala-695006, India. Author
  • Rajesh Ramachandran Department of Microbiology, Center for Research on Molecular Biology and Applied Science, Thiruvananthapuram, Kerala-695006, India. Author
  • Dhanya Chandrasekharan Rajalekshmi Department of Biochemistry, Government Arts and Science College, Kulathur, Kerala-695506, India Author
  • Manju Lekshmy Department of Botany and Biotechnology, St. Xavier’s College, Thumba, Thiruvananthapuram, Kerala, India Author

DOI:

https://doi.org/10.5530/ajphs.2025.15.78

Keywords:

Micrococcus luteus pigment, Parkinson’s disease, SH-SY5Y, Neurite length, BDNF

Abstract

Background: Microorganisms produce a wide range of natural pigments with important bioactive properties. Carotenoid pigments from Micrococcus luteus (M. luteus) have been identified as potential neuroprotective agents. This study aimed to investigate the protective effects of M. luteus pigment in a cellular model of Parkinson’s disease. Methods: Carotenoid pigment was isolated from wild strains of M. luteus and structurally characterized. Its neuroprotective activity was assessed in SH-SY5Y neuroblastoma cells exposed to rotenone. Cell viability, reactive oxygen species (ROS) scavenging, and autophagy modulation were evaluated. Additionally, mRNA expression levels of brain-derived neurotrophic factor (BDNF), a key therapeutic target in Parkinson’s disease, were quantified. Results: M. luteus was identified using MALDI-TOF MS, yielding a score of 2.31. The purified yellow pigment exhibited FTIR peaks at 3269.07 cm⁻¹, 1629.79 cm⁻¹, and 1015.55 cm⁻¹, which align with the characteristics of hydroxylated carotenoids (xanthophyll type). In SH-SY5Y cells, rotenone decreased viability to less than 50%, while co-treatment with pigment restored viability in a concentration-dependent manner, reaching over 90% at 25 μg/mL. Rotenone reduced neurite length by approximately 75%, whereas it was maintained at a concentration of 25 μg/mL pigment. Flow cytometry demonstrated reduced LC3 intensity in the presence of rotenone, which was subsequently restored by co-treatment with pigment, suggesting an increase in autophagy. Rotenone resulted in a marked elevation of ROS levels, whereas pigment treatment significantly reduced these levels in the cells. Rotenone inhibited BDNF expression, whereas co-treatment with pigment restored and elevated BDNF levels to nearly control values. Conclusion: The carotenoid pigment from M. luteus demonstrates significant neuroprotective activity by improving cell viability, scavenging ROS, and enhancing BDNF expression in a Parkinson’s disease cell model. These findings highlight its potential as a natural therapeutic candidate for neurodegenerative disorders

Author Biographies

  • Aiswarya Krishnan, Department of Microbiology, Center for Research on Molecular Biology and Applied Science, Thiruvananthapuram, Kerala-695006, India.

    Research Assistant, Department of Microbiology, Center for Research on Molecular Biology and Applied Science, Thiruvananthapuram, Kerala-695006, India

  • Rajesh Ramachandran, Department of Microbiology, Center for Research on Molecular Biology and Applied Science, Thiruvananthapuram, Kerala-695006, India.

    Director, Center for Research on Molecular Biology and Applied Science, Thiruvananthapuram, Kerala-695006, India

  • Dhanya Chandrasekharan Rajalekshmi, Department of Biochemistry, Government Arts and Science College, Kulathur, Kerala-695506, India

    Professor, Department of Biochemistry, Government Arts and Science College, Kulathoor, Kerala-695506, India

  • Manju Lekshmy, Department of Botany and Biotechnology, St. Xavier’s College, Thumba, Thiruvananthapuram, Kerala, India

    Associate Professor, Department of Botany and Biotechnology, St. Xavier’s College, Thumba, Thiruvananthapuram, Kerala, India

References

1. Balagurunathan R, Selvameenal L, Radhakrishnan M. Antibiotic pigment from desert soil actinomycetes; biological activity, purification and chemical screening. Indian Journal of Pharmaceutical Sciences [Internet]. 2009 Jan 1;71(5):499-504. Available from: https://doi.org/10.4103/0250-474x.58174

2. Mogadem A, Almamary MA, Mahat NA, Jemon K, Ahmad WA, Ali I. Antioxidant Activity Evaluation of Flexirubin Type Pigment from Chryseobacterium artocarpi CECT 8497 and Related Docking Study. Molecules [Internet]. 2021 Feb 12;26(4):979. Available from: https://doi.org/10.3390/molecules26040979

3. Prashanthi K, Suryan S, Varalakshmi KN. In vitro Anticancer Property of Yellow Pigment from Streptomyces griseoaurantiacus JUACT 01. Brazilian Archives of Biology and Technology [Internet]. 2015 Dec 1;58(6):869–76. Available from: https://doi.org/10.1590/s1516-89132015060271

4. Mumtaz R, Bashir S, Numan M, Shinwari ZK, Ali M. Pigments from Soil Bacteria and Their Therapeutic Properties: A Mini Review. Current Microbiology [Internet]. 2018 Sep 3;76(6):783–90. Available from: https://doi.org/10.1007/s00284-018-1557-2

5. Lu Y, Malik A, Venil CK, Dufossé L. Fungal and Bacterial Pigments: Secondary Metabolites with Wide Applications. Frontiers in Microbiology. 2017;8:1113. https://doi.org/10.3389/fmicb.2017.01113

6. Grewal J, Woła̧cewicz M, Pyter W, Joshi N, Drewniak L, Pranaw K. Colorful Treasure From Agro-Industrial Wastes: A Sustainable Chassis for Microbial Pigment Production. Frontiers in Microbiology. 2022;13:832918. doi: 10.3389/fmicb.2022.832918

7. Terao J. Revisiting carotenoids as dietary antioxidants for human health: roles of carotenes and xanthophylls in singlet-oxygen quenching and membrane interaction. Food & Function. 2023;14(8):5789-5800. doi: 10.1039/D3FO02330C

8. Numan M, Bashir S, Mumtaz R, Tayyab S, Rehman NU, Khan AL, et al. Therapeutic applications of bacterial pigments: a review of current status and future opportunities. 3 Biotech [Internet]. 2018 Apr 1;8(4). Available from: https://doi.org/10.1007/s13205-018-1227-x

9. Jagannadham MV, Rao VJ, Shivaji S. The major carotenoid pigment of a psychrotrophic Micrococcus roseus strain: purification, structure, and interaction with synthetic membranes. Journal of Bacteriology [Internet]. 1991 Dec 1;173(24):7911–7. Available from: https://doi.org/10.1128/jb.173.24.7911-7917.1991

10. Greenblatt CL, Baum J, Klein BY, Nachshon S, Koltunov V, Cano RJ. Micrococcus luteus - Survival in Amber. Microbial Ecology [Internet]. 2004 May 28;48(1):120–7. Available from: https://doi.org/10.1007/s00248-003-2016-5

11. Durães F, Pinto M, Sousa E. Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals [Internet]. 2018 May 11;11(2):44. Available from: https://doi.org/10.3390/ph11020044

12. Maia MA, Sousa E. BACE-1 and Γ-Secretase as therapeutic targets for Alzheimer’s disease. Pharmaceuticals [Internet]. 2019 Mar 19;12(1):41. Available from: https://doi.org/10.3390/ph12010041

13. Sancho-Bielsa FJ. Parkinson’s disease: Present and future of cell therapy. Neurology Perspectives [Internet]. 2022 Jan 1;2:S58–68. Available from: https://doi.org/10.1016/j.neurop.2021.07.006

14. Fakhoury M. Role of immunity and inflammation in the pathophysiology of neurodegenerative diseases. Neurodegenerative Diseases [Internet]. 2015 Jan 1;15(2):63–9. Available from: https://doi.org/10.1159/000369933

15. Surekha PY, P D, Mk SJ, S P, Benjamin S. Micrococcus luteus strain BAA2, a novel isolate produces carotenoid pigment [Internet]. Electronic Journal of Biology. 2016 Jan. 12(1):83-89.

16. Surendran S, Suresh G, Vijayakumar N, Ramachandran R. Autophagy and Parkinson’s disease – role of caffeine as autophagic stimulator and anti-apoptotic agent [Internet]. Nepal Journal of Biotechnology. 2023 Dec;11(2):57-64. doi:10.54796/njb.v11i2.262.

17. Jerard C, Michael BP, Chenicheri S, Vijayakumar N, Ramachandran R. Rosmarinic acid-rich fraction from Mentha arvensis synchronizes Bcl/Bax expression and induces G0/G1 arrest in hepatocarcinoma cells. Proceedings of the National Academy of Sciences India Section B Biological Sciences [Internet]. 2019 Jul 15;90(3):515–22. Available from: https://doi.org/10.1007/s40011-019-01122-9

18. Ramachandran R, Saraswathy M. Up-regulation of nuclear related factor 2 (NRF2) and antioxidant responsive elements by metformin protects hepatocytes against the acetaminophen toxicity. Toxicology Research [Internet]. 2014 Jun 24;3(5):350-8. Available from: https://doi.org/10.1039/c4tx00032c

19. Hancock MK, Kopp L, Kaur N, Hanson BJ. A facile method for simultaneously measuring neuronal cell viability and neurite outgrowth. Current Chemical Genomics and Translational Medicine [Internet]. 2015 Feb 27;9(1):6–16. Available from: https://doi.org/10.2174/2213988501509010006

20. Almazrooei SS, Ghazala W. Characterization of the glyceraldehyde-3-phosphate dehydrogenase gene from the desert plant Haloxylon salicornicum using RT-PCR amplification and sequencing. Journal of King Saud University-Science. 2018;30(4):552-60. doi:10.1016/j.jksus.2017.07.004.

21. Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, Stringer T, Ulja D, Karuppagounder SS, Holson EB, Ratan RR, Ninan I, Chao MV. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. eLife. 2016;5:e15092. doi:10.7554/eLife.15092.

22. Huang C, Zhang Z, Cui W. Marine-Derived natural compounds for the treatment of Parkinson’s disease. Marine Drugs [Internet]. 2019 Apr 11;17(4):221. Available from: https://doi.org/10.3390/md17040221

23. Iarkov A, Barreto GE, Grizzell JA, Echeverria V. Strategies for the treatment of Parkinson’s Disease: Beyond dopamine. Frontiers in Aging Neuroscience [Internet]. 2020 Jan 31;12. Available from: https://doi.org/10.3389/fnagi.2020.00004

24. Mythri RB, Harish G, Bharath MM. Therapeutic potential of natural products in Parkinson’s disease. Recent Patents on Endocrine Metabolic & Immune Drug Discovery [Internet]. 2012 Aug 1;6(3):181–200. Available from: https://doi.org/10.2174/187221412802481793

25. Photometry & reflectometry [Internet]. Sigma-Aldrich. Available from: URL https://www.sigmaaldrich.com/IN/en/technical-documents/technical-article/analytical-chemistry/photometry-and-reflectometry/ir-spectrum-table

26. Jain J, Hasan W, Biswas P, Yadav RS, Jat D. Neuroprotective effect of quercetin against rotenone‐induced neuroinflammation and alterations in mice behavior. Journal of Biochemical and Molecular Toxicology [Internet]. 2022 Jul 13;36(10):e23165. Available from: https://doi.org/10.1002/jbt.23165

27. Oladele JO, Oladiji AT, Oladele OT, Oyeleke OM. Reactive oxygen species in neurodegenerative diseases: Implications in pathogenesis and treatment strategies. In: Biochemistry [Internet]. 2021. Available from: https://doi.org/10.5772/intechopen.99976

28. Lin TK, Chen SD, Chuang YC, Lin HY, Huang CR, Chuang JH, et al. Resveratrol Partially Prevents Rotenone-Induced Neurotoxicity in Dopaminergic SH-SY5Y Cells through Induction of Heme Oxygenase-1 Dependent Autophagy. International Journal of Molecular Sciences [Internet]. 2014 Jan 22;15(1):1625–46. Available from: https://doi.org/10.3390/ijms15011625

29. Feng J, Zheng Y, Guo M, Ares I, Martínez M, Lopez-Torres B, et al. Oxidative stress, the blood–brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants. Acta Pharmaceutica Sinica B [Internet]. 2023 Jul 16;13(10):3988–4024. Available from: https://doi.org/10.1016/j.apsb.2023.07.010

30. Mader BJ, Pivtoraiko VN, Flippo HM, Klocke BJ, Roth KA, Mangieri LR, et al. Rotenone inhibits autophagic flux prior to inducing cell death. ACS Chemical Neuroscience [Internet]. 2012 Sep 13;3(12):1063–72. Available from: https://doi.org/10.1021/cn300145z

31. Xiong N, Xiong J, Jia M, Liu L, Zhang X, Chen Z, et al. The role of autophagy in Parkinson’s disease: rotenone-based modeling. Behavioral and Brain Functions [Internet]. 2013 Mar 15;9(13). Available from: https://doi.org/10.1186/1744-9081-9-13

32. Djajadikerta A, Keshri S, Pavel M, Prestil R, Ryan L, Rubinsztein DC. Autophagy induction as a therapeutic strategy for neurodegenerative diseases. Journal of Molecular Biology [Internet]. 2019 Dec 27;432(8):2799–821. Available from: https://doi.org/10.1016/j.jmb.2019.12.035

33. Ibarra-Gutiérrez MT, Serrano-García N, Orozco-Ibarra M. Rotenone-Induced Model of Parkinson’s Disease: Beyond Mitochondrial complex I inhibition. Molecular Neurobiology [Internet]. 2023 Jan 3;60(4):1929–48. Available from: https://doi.org/10.1007/s12035-022-03193-8

34. Nahar L, Charoensup R, Kalieva K, Habibi E, Guo M, Wang D, et al. Natural products in neurodegenerative diseases: recent advances and future outlook. Frontiers in Pharmacology [Internet]. 2025 Mar 19;16. Available from: https://doi.org/10.3389/fphar.2025.1529194

35. Shaikh S, Ahmad K, Ahmad SS, Lee EJ, Lim JH, Beg MMA, et al. Natural products in therapeutic management of multineurodegenerative disorders by targeting autophagy. Oxidative Medicine and Cellular Longevity [Internet]. 2021 Jan 1;2021(1):6347792. Available from: https://doi.org/10.1155/2021/6347792

36. Azman KF, Zakaria R. Brain-Derived Neurotrophic Factor (BDNF) in Huntington’s Disease: Neurobiology and Therapeutic Potential. Current Neuropharmacology [Internet]. 2025 Jan 7;23(4):384–403. Available from: https://doi.org/10.2174/1570159x22666240530105516

37. Huang YX, Zhang QL, Huang CL, Wu WQ, Sun JW. Association of decreased serum BDNF with restless legs syndrome in Parkinson’s disease patients. Frontiers in Neurology [Internet]. 2021 Oct 26;12. Available from: https://doi.org/10.3389/fneur.2021.734570

38. Azman KF, Zakaria R. Recent advances on the role of Brain-Derived Neurotrophic Factor (BDNF) in neurodegenerative diseases. International Journal of Molecular Sciences [Internet]. 2022 Jun 19;23(12):6827. Available from: https://doi.org/10.3390/ijms23126827

39. Jiang L, Zhang H, Wang C, Ming F, Shi X, Yang M. Serum level of brain-derived neurotrophic factor in Parkinson’s disease: a meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry [Internet]. 2018 Jul 11;88:168–74. Available from: https://doi.org/10.1016/j.pnpbp.2018.07.010

40. Xu B, Bai L, Chen L, Tong R, Feng Y, Shi J. Terpenoid natural products exert neuroprotection via the PI3K/Akt pathway. Frontiers in Pharmacology [Internet]. 2022 Oct 13;13. Available from: https://doi.org/10.3389/fphar.2022.1036506

Paul R, Mazumder MK, Nath J, Deb S, Paul S, Bhattacharya P, Borah A. Lycopene – A pleiotropic

Downloads

Published

2025-06-30

Issue

Vol. 15 No. 2 (2025)

Section

Articles

How to Cite

Carotenoid pigment from Micrococcus luteus confers neuroprotection in a cellular model of Parkinson’s disease via BDNF upregulation and oxidative stress reduction. (2025). Asian Journal of Pharmaceutical and Health Sciences, 15(2), 3061-3072. https://doi.org/10.5530/ajphs.2025.15.78