Skip to main content
Springer Nature Link
Log in

Synergistic neuroprotection by phytocompounds of Bacopa monnieri in scopolamine-induced Alzheimer’s disease mice model

  • Original Article
  • Published:
Save article
View saved research
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Millions of people around the globe are affected by Alzheimer’s disease (AD). This crippling condition has no treatment despite intensive studies. Some phytocompounds have been shown to protect against Alzheimer’s in recent studies.

Methods

Thus, this work aimed to examine Bacopa monnieri phytocompounds’ synergistic effects on neurodegeneration, antioxidant activity, and cognition in the scopolamine-induced AD mice model. The toxicity study of two phytocompounds: quercetin and bacopaside X revealed an LD50 of more than 2000 mg/kg since no deaths occurred.

Results

The neuroprotection experiment consists of 6 groups i.e., control (saline), scopolamine (1 mg/kg), donepezil (5 mg/kg), Q (25 mg/kg), BX (20 mg/kg), and Q + BX (25 mg/kg + 20 mg/kg). Visual behavioral assessment using the Morris water maze showed that animals in the diseased model group (scopolamine) moved more slowly toward the platform and exhibited greater thigmotaxis behavior than the treatment and control groups. Likewise, the concentration of biochemical NO, GSH, and MDA improved in treatment groups concerning the diseased group. mRNA levels of different marker genes including ChAT, IL-1α, IL-1 β, TNF α, tau, and β secretase (BACE1) improved in treatment groups with respect to the disease group.

Conclusion

Both bacopaside X and quercetin synergistically have shown promising results in neuroprotection. Therefore, it is suggested that Q and BX may work synergistically due to their antioxidant and neuroprotective property.

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

Access this article

Log in via an institution

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

Data availability

The data used to support the findings of this study are included within the supplementary information file(s).

References

  1. Khalil M et al (2018) Neurofilaments as biomarkers in neurological disorders. Nat Reviews Neurol 14(10):577–589

    Article  CAS  Google Scholar 

  2. Anwar MM et al (2022) Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: early approaches for therapeutic intervention. Front NeuroSci, 16

  3. WHO (2023) Dementia https://www.who.int/news-room/fact-sheets/detail/dementia

  4. Bhat AH et al (2015) Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother 74:101–110

    Article  CAS  PubMed  Google Scholar 

  5. Dai Y et al (2022) Amyloid-beta targeted therapeutic approaches for Alzheimer’s disease: long road ahead. Curr Drug Targets 23(11):1040–1056

    Article  CAS  PubMed  Google Scholar 

  6. Fjell AM et al (2014) What is normal in normal aging? Effects of aging, amyloid and Alzheimer’s disease on the cerebral cortex and the hippocampus. Prog Neurobiol 117:20–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sibat HF, Valdés L (2013) Uncommon clinical manifestations of cysticercosis. Novel Aspects on Cysticercosis and Neurocysticercosis 8:199–233

    Google Scholar 

  8. Prasad K (2019) AGE–RAGE stress: a changing landscape in pathology and treatment of Alzheimer’s disease. Mol Cell Biochem 459(1–2):95–112

    Article  CAS  PubMed  Google Scholar 

  9. Bateman RJ et al (2011) Autosomal-dominant Alzheimer’s disease: a review and proposal for the prevention of Alzheimer’s disease, vol 3. Alzheimer’s research & therapy, pp 1–13. 1

  10. Andrews SJ et al (2023) The complex genetic architecture of Alzheimer’s disease: novel insights and future directions. EBioMedicine, 90

  11. Bertram L, Tanzi RE (2008) Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 9(10):768–778

    Article  CAS  PubMed  Google Scholar 

  12. Alam J, Sharma L (2019) Potential enzymatic targets in Alzheimer’s: a comprehensive review. Curr Drug Targets 20(3):316–339

    Article  CAS  PubMed  Google Scholar 

  13. Martorana A, Esposito Z, Koch G (2010) Beyond the cholinergic hypothesis: do current drugs work in Alzheimer’s disease? vol 16. CNS neuroscience & therapeutics, pp 235–245. 4

  14. Vecchio I et al (2021) The state of the art on acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease. J Cent Nerv Syst Disease 13:11795735211029113

    Google Scholar 

  15. Chen Z-R et al (2022) Role of cholinergic signaling in Alzheimer’s disease. Molecules 27(6):1816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hampel H et al (2018) The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain 141(7):1917–1933

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wess J, Eglen RM, Gautam D (2007) Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nat Rev Drug Discovery 6(9):721–733

    Article  CAS  PubMed  Google Scholar 

  18. Alhazmi HA, Albratty M (2022) An update on the novel and approved drugs for Alzheimer disease. Saudi Pharm J,

  19. Prasansuklab A, Brimson JM, Tencomnao T (2020) Potential thai medicinal plants for neurodegenerative diseases: a review focusing on the anti-glutamate toxicity effect. J Traditional Complement Med 10(3):301–308

    Article  Google Scholar 

  20. Simpson T, Pase M, Stough C (2015) Bacopa monnieri as an antioxidant therapy to reduce oxidative stress in the aging brain Evidence-based complementary and alternative medicine, 2015

  21. Chaudhari KS et al (2017) Neurocognitive effect of nootropic drug Brahmi (Bacopa monnieri) in Alzheimer’s disease. Annals of neurosciences 24(2):111–122

    Article  PubMed  PubMed Central  Google Scholar 

  22. Fatima U et al (2022) Investigating neuroprotective roles of Bacopa monnieri extracts: mechanistic insights and therapeutic implications. Biomed Pharmacother 153:113469

    Article  CAS  PubMed  Google Scholar 

  23. Fatima U et al (2022) Pharmacological attributes of Bacopa monnieri extract: current updates and clinical manifestation. Front Nutr 9:972379

    Article  PubMed  PubMed Central  Google Scholar 

  24. Basheer A et al (2022) Use of Bacopa monnieri in the treatment of Dementia due to Alzheimer Disease: systematic review of Randomized controlled trials. Interact J Med Res 11(2):e38542

    Article  PubMed  PubMed Central  Google Scholar 

  25. Abdul Manap AS et al (2019) Bacopa monnieri, a neuroprotective lead in Alzheimer disease: a review on its properties, mechanisms of action, and preclinical and clinical studies. Drug target insights 13:1177392819866412

    Article  PubMed  PubMed Central  Google Scholar 

  26. Nandy S, Dey A, Mukherjeeb A (2019) Advances in dammarane-type triterpenoid saponins from Bacopa monnieri: structure, bioactivity, biotechnology and neuroprotection. Stud Nat Prod Chem 63:489–533

    Article  CAS  Google Scholar 

  27. Sangeet S, Khan A (2021) In-silico studies of Neurocognitive and Neuropharmacological effect of Bacopa monnieri (L.) bioRxiv, : p. 2021.01. 20.427542

  28. Brimson JM et al (2021) The effectiveness of Bacopa monnieri (Linn.) Wettst. As a nootropic, neuroprotective, or antidepressant supplement: analysis of the available clinical data. Sci Rep 11(1):596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Giacobini E (2003) Cholinergic function and alzheimer’s disease. Int J Geriatr Psychiatry 18(S1):S1–S5

    Article  PubMed  Google Scholar 

  30. Yusufzai SK et al (2018) Molecular docking studies of coumarin hybrids as potential acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A/B and β-amyloid inhibitors for Alzheimer’s disease. Chem Cent J 12(1):1–57

    Article  Google Scholar 

  31. Levin LA et al (2022) Neuroprotection in neurodegenerations of the brain and eye: Lessons from the past and directions for the future. Front Neurol 13:964197

    Article  PubMed  PubMed Central  Google Scholar 

  32. Banerjee S et al (2021) Bacosides from Bacopa monnieri extract: an overview of the effects on neurological disorders. Phytother Res 35(10):5668–5679

    Article  PubMed  Google Scholar 

  33. Guideline P-BT (2001) OECD guideline for the testing of chemicals. The Hershberger 601:858

    Google Scholar 

  34. Vaghasiya Y, Dave R, Chanda S (2011) Phytochemical analysis of some medicinal plants from western region of India. Res J Med Plant 5(5):567–576

    Article  Google Scholar 

  35. Mukinda JT, Syce JA (2007) Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents. J Ethnopharmacol 112(1):138–144

    Article  CAS  PubMed  Google Scholar 

  36. Eppley BL, Woodell JE, Higgins J (2004) Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 114(6):1502–1508

    Article  PubMed  Google Scholar 

  37. Orlandi M, Graziani F, D’Aiuto F (2020) Periodontal therapy and cardiovascular risk. Periodontol 2000 83(1):107–124

    Article  PubMed  Google Scholar 

  38. Lowe D et al (2022) Alkaline phosphatase, in StatPearls [internet]. StatPearls Publishing

  39. Chanda S et al (2012) Acute oral toxicity of Polyalthia longifolia var. Pendula leaf extract in Wistar albino rats. Pharm Biol 50(11):1408–1415

    Article  PubMed  Google Scholar 

  40. Harizal S et al (2010) Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in rodent. J Ethnopharmacol 131(2):404–409

    Article  CAS  PubMed  Google Scholar 

  41. Salawu O et al (2009) Acute and sub-acute toxicological evaluation of the methanolic stem bark extract of Crossopteryx febrifuga in rats. Afr J Pharm and Pharmacol 3(12):621–626

    Google Scholar 

  42. Madhyastha S et al (2011) Neuroprotective effects of Mucuna pruriens against stress-induced oxidative damage. J Physiological Biomedical Sci 24(2):28–33

    Google Scholar 

  43. Atanu FO et al (2021) Evaluation of antimalarial potential of extracts from Alstonia boonei and Carica papaya in Plasmodium berghei-infected mice Evidence-Based Complementary and Alternative Medicine, 2021: p. 1–11

  44. Chen J et al (2019) Neuroprotective effects of red ginseng saponins in scopolamine-treated rats and activity screening based on pharmacokinetics. Molecules 24(11):2136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Alikatte KL et al (2012) Antiamnesic activity of Syzygium cumini against scopolamine induced spatial memory impairments in rats. Brain Develop 34(10):844–851

    Article  Google Scholar 

  46. Cai H et al (2001) BACE1 is the major β-secretase for generation of Aβ peptides by neurons. Nat Neurosci 4(3):233–234

    Article  CAS  PubMed  Google Scholar 

  47. Wang F et al (2021) Mitochondrial protein translation: emerging roles and clinical significance in disease. Front Cell Dev Biology 9:675465

    Article  Google Scholar 

  48. Das B, Yan R (2017) Role of BACE1 in Alzheimer’s synaptic function. Translational neurodegeneration 6:1–8

    Article  Google Scholar 

  49. Decourt B, Lahiri DK, Sabbagh MN (2017) Targeting tumor necrosis factor alpha for Alzheimer’s disease. Curr Alzheimer Res 14(4):412–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zaky AM et al (2017) Tumor-vessel relationships in pancreatic ductal adenocarcinoma at multidetector CT: different classification systems and their influence on treatment planning. Radiographics 37(1):93–112

    Article  PubMed  Google Scholar 

  51. Shi C, Pamer EG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11(11):762–774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Griffin W et al (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci 86(19):7611–7615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Depino A et al (2005) Differential effects of interleukin-1β on neurotoxicity, cytokine induction and glial reaction in specific brain regions. J Neuroimmunol 168(1–2):96–110

    Article  CAS  PubMed  Google Scholar 

  54. Pugh KR et al (2001) Neurobiological studies of reading and reading disability. J Commun Disord 34(6):479–492

    Article  CAS  PubMed  Google Scholar 

  55. Gad SC, Chengelis CP (1997) Acute toxicology testing. Academic Press

  56. Kraus SI et al (2023) Toxicological and pharmacological effects of Eugenia brasiliensis Lam.(Myrtaceae) leaves in mice. J Ethnopharmacol 309:116309

    Article  CAS  PubMed  Google Scholar 

  57. Manwani B et al (2011) Functional recovery in aging mice after experimental stroke. Brain Behav Immun 25(8):1689–1700

    Article  PubMed  PubMed Central  Google Scholar 

  58. Worasuttayangkurn L et al (2012) Safety evaluation of longan seed extract: acute and repeated oral administration. Food Chem Toxicol 50(11):3949–3955

    Article  CAS  PubMed  Google Scholar 

  59. Sabogal-Guáqueta AM et al (2015) The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology 93:134–145

    Article  PubMed  Google Scholar 

  60. Palle S, Neerati P (2017) Quercetin nanoparticles attenuates scopolamine induced spatial memory deficits and pathological damages in rats. Bull Fac Pharm Cairo Univ 55(1):101–106

    Google Scholar 

  61. Singh B et al (2022) Bacopaside-I ameliorates motor dysfunction and neurodegeneration in rat model of parkinson’s disease

  62. Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11(1):47–60

    Article  CAS  PubMed  Google Scholar 

  63. Bromley-Brits K, Deng Y, Song W Morris water maze test for learning and memory deficits in Alzheimer’s disease model mice. J visualized experiments: JoVE, 2011(53).

  64. Ellman G, Courtney K (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacal 7a:88–95

    Article  Google Scholar 

  65. Wilbur K (1949) The thiobarbituric acid reagent as a test for the oxidation of unsaturated fatty acids by various agents. Archs Biochem Biophys 24:305–313

    CAS  Google Scholar 

  66. Sun J et al (2003) Measurement of nitric oxide production in biological systems by using Griess reaction assay. Sensors 3(8):276–284

    Article  CAS  Google Scholar 

  67. Farhat F et al (2021) Akt/GSK3β/Nrf2/HO-1 pathway activation by flurbiprofen protects the hippocampal neurons in a rat model of glutamate excitotoxicity. Neuropharmacology 196:108654

    Article  CAS  PubMed  Google Scholar 

  68. Hestrin S (1949) The reaction of acetylcholine and other carboxylic acid derivatives with hydroxylamine, and its analytical application. J Biol Chem 180(1):249–261

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors extend their appreciation to the Researchers Supporting Project number (RSP-2023R369), King Saud University, Riyadh, Saudi Arabia. The authors are thankful to National Institute for Genomics and Advanced Biotechnology (NIGAB), Islamabad, Pakistan for facilitating and providing research funds throughout this study.

Funding

This research received no external funding.

Author information

Authors and Affiliations

  1. Department of Plant Genomics and Biotechnology, PARC Institute of Advanced Studies in Agriculture, Affiliated with Quaid-e-Azam University, National Agriculture Research Centre, Islamabad, Pakistan

    Shehla Shoukat

  2. National Institute for Genomics and Advanced Biotechnology, National Agriculture Research Centre, Islamabad, Pakistan

    Muhammad Amir Zia, Muhammad Uzair & Shaukat Ali

  3. Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Roua A. Alsubki

  4. Department of Biotechnology, University of Gujrat, Gujrat, Pakistan

    Kaynat Sajid

  5. Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, Pakistan

    Sana Shoukat

  6. Department of Biochemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    KOTB A. Attia

  7. Department of Plant Breeding and Genetics, University of Haripur, Haripur, Pakistan

    Sajid Fiaz & Itoh Kimiko

  8. Institute of Science and Technology, Niigata University, Ikarashi-2, Nishi-ku, Niigata, 950-2181, Japan

    Itoh Kimiko

  9. Pakistan Agriculture Research Council, Islamabad, Pakistan

    Ghulam Muhammad Ali

Authors
  1. Shehla Shoukat
    View author publications

    Search author on:PubMed Google Scholar

  2. Muhammad Amir Zia
    View author publications

    Search author on:PubMed Google Scholar

  3. Muhammad Uzair
    View author publications

    Search author on:PubMed Google Scholar

  4. Roua A. Alsubki
    View author publications

    Search author on:PubMed Google Scholar

  5. Kaynat Sajid
    View author publications

    Search author on:PubMed Google Scholar

  6. Sana Shoukat
    View author publications

    Search author on:PubMed Google Scholar

  7. KOTB A. Attia
    View author publications

    Search author on:PubMed Google Scholar

  8. Sajid Fiaz
    View author publications

    Search author on:PubMed Google Scholar

  9. Shaukat Ali
    View author publications

    Search author on:PubMed Google Scholar

  10. Itoh Kimiko
    View author publications

    Search author on:PubMed Google Scholar

  11. Ghulam Muhammad Ali
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Conceptualization of study, S.S., M.A.Z, and S.A.; methodology, S.S.; software, S.S.; validation, M.A.Z., S.A., S.S., and S.S.; formal analysis, S.S., S.F., and M.U.; investigation, S.S.; resources, S.A.; writing—original draft preparation, S.S., K.A.A, I.K, K.S, M.A.Z; writing—review and editing, S.S., S.S., S.A., R.A.A., and G.M.A.; visualization, M.A.Z., S.S., and M.U.; supervision, S.A.; project administration, S.A.; funding acquisition, R.A.A., S.F., and M.U. All authors have read and agreed to the published version of the manuscript.”

Corresponding authors

Correspondence to Shehla Shoukat or Shaukat Ali.

Ethics declarations

Ethics approval and consent to participate

Ethical approval statement/approval letter has been attached. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shoukat, S., Zia, M.A., Uzair, M. et al. Synergistic neuroprotection by phytocompounds of Bacopa monnieri in scopolamine-induced Alzheimer’s disease mice model. Mol Biol Rep 50, 7967–7979 (2023). https://doi.org/10.1007/s11033-023-08674-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1007/s11033-023-08674-0

Keywords

Profiles

  1. KOTB A. Attia View author profile
  2. Itoh Kimiko View author profile