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From Bench to Bedside: Unveiling the Effects of Phloroglucinol as a Promising Neuroprotective Agent in the Battle Against Neurodegenerative Disorders

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Abstract

Purpose of Review

Phloroglucinol (PG) is a potent secondary metabolite found in various organisms, with extensive applications in medicine since its discovery in the nineteenth century. Research has demonstrated its diverse properties, including anti-inflammatory, antioxidant, anti-viral, anti-cancer, and anthelmintic effects. In clinical settings, it alleviates pain by relaxing the gastrointestinal, biliary, and urinary systems. Despite its broad pharmacological potential, its use in treating neurodegenerative diseases (ND) remains underexplored. This study systematically explores PG’s role in ND management, utilizing data exclusively from reputable sources like PubMed, Google Scholar, Scopus, ScienceDirect, and SpringerLink, and adhering to PRISMA guidelines to provide structured insights.

Recent findings

The review emphasizes PG’s significant role in treating various neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). PG offers cytoprotective effects by preventing dendritic spine density loss in AD, reducing ROS levels in PD and ALS, and inhibiting amyloid aggregate formation in HD. These benefits stem from its powerful antioxidant properties, which alleviate cerebral oxidative stress. Overall, PG stands out as an affordable and readily accessible resource with promising pharmaceutical applications for treating NDs.

Summary

This study underscores the prospect of PG serving as a wellspring for innovative drugs catering to the intricate demands of neurodegenerative conditions. Nevertheless, further research is necessary to thoroughly assess its clinical effectiveness in human subjects to ensure its widespread acceptance in clinical practice.

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Data Availability

Not applicable.

Abbreviations

PG:

Phloroglucinol

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

HD:

Huntington disease

ALS,:

Amyotropic lateral sclerosis

ROS:

Reactive oxygen species

NOS:

Nitric oxide synthase

RNS:

Reactive nitrogen species

DALYs:

Disability-adjusted life ears

ADME:

Absorption, distribution, metabolism, excretion

NADP+ :

NADPH

SOD:

Superoxide dismutase

CAT:

Catalase

GSH:

Glutathione

GST:

Glutathione S-transferases

GPx1:

Glutathione peroxidase 1

HO-1:

Heme oxygenase 1

Nrf2 :

Nuclear factor erythroid 2–related factor 2

H2O2 :

Hydrogen peroxide

ATP:

Adenosine triphosphate

APP:

Amyloid precursor protein

NTF:

Neurofibrillary tangles

Aβ:

Amyloid beta

4HNE:

4-Hydroxynonenal protein

6-OHDA:

6-Hydroxydopamine

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Muddapu VR, Dharshini SAP, Chakravarthy VS, Gromiha MM. Neurodegenerative diseases - is metabolic deficiency the root cause? Front Neurosci. 2020;14:213. https://doi.org/10.3389/fnins.2020.00213.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Checkoway H, Kelada SN, Costa LG. Neurodegenerative diseases. Biol Med. 2011;407–419. https://doi.org/10.1002/0471758043.CH15

  3. Pereira TMC, Côco LZ, Ton AMM, Meyrelles SS, Campos-Toimil M, Campagnaro BP, Vasquez EC. The emerging scenario of the gut–brain axis: the therapeutic actions of the new actor kefir against neurodegenerative diseases. Antiox. 2021;10:1845. https://doi.org/10.3390/ANTIOX10111845.

    Article  CAS  Google Scholar 

  4. Brown RC, Lockwood AH, Sonawane BR. Neurodegenerative diseases: an overview of environmental risk factors. Environ Health Perspect. 2005;113:1250–6. https://doi.org/10.1289/EHP.7567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ding C, Wu Y, Chen X, Chen Y, Wu Z. Global, regional, and national burden and attributable risk factors of neurological disorders: the Global Burden of Disease study 1990–2019. Front Public Health. 2022;10:321. https://doi.org/10.3389/fpubh.2022.952161.

    Article  Google Scholar 

  6. Mayeux R, Stern Y. Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med. 2012;8:a006293. https://doi.org/10.1101/cshperspect.a006239.

    Article  Google Scholar 

  7. Erkkinen M, Kim M, Geschwind M. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harb Perspect Biol. 2018;10:a033118. https://doi.org/10.1101/cshperspect.a033118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Anonymous (2022) Parkinson’s foundation: Statistics https://www.parkinson.org/understanding-parkinsons/statistics#:~:text=A%202022%20Parkinson’s%20Foundation%2Dbacked,rate%20of%2060%2C000%20diagnoses%20annually Accessed 10.1.23

  9. Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N. The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis. Mov Disord. 2012;27:1083–91. https://doi.org/10.1002/mds.25075.

    Article  PubMed  Google Scholar 

  10. Xu L, Liu T, Liu L, Yao X, Chen L, Fan D, Zhan S, Wang S. Global variation in prevalence and incidence of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol. 2020;267:944–53. https://doi.org/10.1007/s00415-019-09652-y.

    Article  PubMed  Google Scholar 

  11. Nandi A, Counts N, Chen S, Seligman B, Tortorice D, Vigo D, Bloom D. Global and regional projections of the economic burden of Alzheimer’s disease and related dementias from 2019 to 2050: a value of statistical life approach. E Clinic Med. 2022;51:101580. https://doi.org/10.1016/j.eclinm.2022.101580.

    Article  Google Scholar 

  12. Miller J, Das V. Potential for treatment of neurodegenerative diseases with natural products or synthetic compounds that stabilize microtubules. Curr Pharm Des. 2020;26:4362–72.

    Article  CAS  PubMed  Google Scholar 

  13. Zahoor I, Shafi A, Haq E (2018) Chapter 7: pharmacological treatment of Parkinson’s disease. In: Stoker TB, Greenland JC (Eds) Parkinson’s disease: pathogenesis and clinical aspects, Exon publications, Australia, pp 431–450. https://doi.org/10.15586/codonpublications.parkinsonsdisease.2018.ch7

  14. Mathur S, Gawas C, Ahmad IZ, Wani M, Tabassum H. Neurodegenerative disorders: Assessing the impact of natural vs drug-induced treatment options. Aging Med (Milton). 2023;6:82–97. https://doi.org/10.1002/agm2.12243.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Duraes F, Pinto M, Sousa E. Old drugs as new treatments for neurodegenerative diseases. Pharm (Basel). 2018;11:44.

    Article  Google Scholar 

  16. Tsolaki M, Arcan C, Zahid S. (2023) Editorial: the role of natural products in neurological disorders. Front Neurol. 2023;14:125–30. https://doi.org/10.3389/fneur.2023.1163282.

    Article  Google Scholar 

  17. Zhao J, Wang D, Cui W, Chen H. Editorial: natural products in the treatment of neurological diseases: identification of novel active compounds and therapeutic targets. Front Pharmacol. 2023;14:482–90. https://doi.org/10.3389/fphar.2023.1294625.

    Article  Google Scholar 

  18. Sharma R, Singla RK, Banerjee S, Sharma R. Revisiting licorice as a functional food in the management of neurological disorders: bench to trend. Neurosci Biobehav Rev. 2023;155:105452. https://doi.org/10.1016/j.neubiorev.2023.105452.

    Article  CAS  PubMed  Google Scholar 

  19. Raina K, Kumari R, Thakur P, Sharma R, Singh R, Thankur A, Anand V, Sharma R, Chaudhary A. Mechanistic role and potential of Ayurvedic herbs as anti-aging therapies. Drug Metabol Pers Ther. 2023;38(3):211–26.

    Article  CAS  Google Scholar 

  20. Thakur P, Kumar R, Choudhary N, Sharma R, Chaudhury A. Network pharmacology on mechanistic role of Thymus linearis Benth. against gastrointestinal and neurological diseases. Phytomedicine. 2023;121:155098.

    Article  CAS  PubMed  Google Scholar 

  21. Abdul Manap AS, Vijayabalan S, Madhavan P, Chia YY, Arya A, Wong EH, Rizwan F, Bindal U, Koshy S. Bacopa monnieri, a Neuroprotective lead in Alzheimer Disease: A review on its properties, mechanisms of action, and preclinical and clinical studies. Drug Target Insights. 2019;13:1177392819866412. https://doi.org/10.1177/1177392819866412.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Weinreb O, Mandel S, Amit T, Youdim MB. Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s diseases. J NutrBiochem. 2004;15(9):506–16. https://doi.org/10.1016/j.jnutbio.2004.05.002.

    Article  CAS  Google Scholar 

  23. Hossain S, Hashimoto M, Katakura M, Al Mamun A, Shido O. Medicinal value of asiaticoside for Alzheimer’s disease as assessed using single-molecule-detection fluorescence correlation spectroscopy, laser-scanning microscopy, transmission electron microscopy, and in silico docking. BMC Complement Altern Med. 2015;15:118. https://doi.org/10.1186/s12906-015-0620-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Xu CL, Qu R, Zhang J, Li LF, Ma SP. Neuroprotective effects of madecassoside in early stage of Parkinson’s disease induced by MPTP in rats. Fitoterapia. 2013;90:112–8. https://doi.org/10.1016/j.fitote.2013.07.009.

    Article  CAS  PubMed  Google Scholar 

  25. Hu S, Maiti P, Ma Q, Zuo X, Jones MR, Cole GM, Frautschy SA. Clinical development of curcumin in neurodegenerative disease. Expert Rev Neurother. 2015;15(6):629–37. https://doi.org/10.1586/14737175.2015.1044981.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Niu TT, Yuan BY, Liu GZ. Ginkgolides and bilobalide for treatment of Alzheimer’s disease and COVID-19: potential mechanisms of action. Eur Rev Med Pharmacol Sci. 2022;26(24):9502–10. https://doi.org/10.26355/eurrev_202212_30702.

    Article  PubMed  Google Scholar 

  27. Yuan X, Yan F, Gao LH, Ma QH, Wang J. Hypericin as a potential drug for treating Alzheimer’s disease and type 2 diabetes with a view to drug repositioning. CNS Neurosci Ther. 2023;29:3307–21. https://doi.org/10.1111/cns.14260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sun Y, Yang Y, Liu S, Yang S, Chen C, Lin M, Zeng Q, Long J, Yao J, Yi F, Meng L, Ai Q, Chen N. New therapeutic approaches to and mechanisms of ginsenoside Rg1 against neurological diseases. Cells. 2022;11(16):2529. https://doi.org/10.3390/cells11162529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mohd Sairazi NS, Sirajudeen KNS. Natural products and their bioactive compounds: neuroprotective potentials against neurodegenerative diseases. Evid-based Complement Alternat Med. 2020;6565396. https://doi.org/10.1155/2020/6565396.

  30. Di Paolo M, Papi L, Gori F, Turillazzi E. Natural products in neurodegenerative diseases: a great promise but an ethical challenge. Int J Mol Sci. 2019;20(20):5170. https://doi.org/10.3390/ijms20205170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Saraiva C, Praça C, Ferreira R, Santos T, Ferreira L, Bernardino L. Nanoparticle-mediated brain drug delivery: overcoming blood–brain barrier to treat neurodegenerative diseases. J Control Release. 2016;235:34–47.

    Article  CAS  PubMed  Google Scholar 

  32. Smith A, Giunta B, Bickford PC, Fountain M, Tan J, Shytle RD. Nanolipidic particles improve the bioavailability and alpha-secretase inducing ability of epigallocatechin-3-gallate (EGCG) for the treatment of Alzheimer’s disease. Int J Pharm. 2010;389(1–2):207–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bhatt R, Singh D, Prakash A, Mishra N. Development, characterization and nasal delivery of rosmarinic acid loaded solid lipid nanoparticles for the effective management of Huntington’s disease. Drug Deliv. 2015;22(7):931–9.

    Article  CAS  PubMed  Google Scholar 

  34. Del Prado-Audelo ML, Caballero-Floran IH, MezaToledo JA, et al. Formulations of curcumin nanoparticles for brain diseases. Biomolecules. 2019;9:56.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Islam F, Islam MM, Khan Meem AF, Nafady MH, Islam MR, Akter A, Mitra S, Alhumaydhi FA, Emran TB, Khusro A, Simal-Gandara J, Eftekhari A, Karimi F, Baghayeri M. Multifaceted role of polyphenols in the treatment and management of neurodegenerative diseases. Chemosphere. 2022;307(Pt 3):136020. https://doi.org/10.1016/j.chemosphere.2022.136020.

    Article  CAS  PubMed  Google Scholar 

  36. Li Z, Zhao T, Shi M, Wei Y, Huang X, Shen J, Zhang X, Xie Z, Huang P, Yuan K, Li Z, Li N, Qin D. Polyphenols: natural food grade biomolecules for treating neurodegenerative diseases from a multi-target perspective. Front Nutr. 2023;10:1139558. https://doi.org/10.3389/fnut.2023.1139558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Singh IP, Sidana J, Bharate SB, Foley WJ. Phloroglucinol compounds of natural origin: synthetic aspects. Rep Nat Prod. 2010;27:393–416.

    Article  CAS  Google Scholar 

  38. Blanchard C, Pouchain D, Vanderkam P, Perault-Pochat MC, Boussageon R, Vaillant-Roussel H. Efficacy of phloroglucinol for treatment of abdominal pain: a systematic review of literature and meta-analysis of randomised controlled trials versus placebo. Eur J ClinPharmacol. 2018;74:541–8. https://doi.org/10.1007/S00228-018-2416-6.

    Article  CAS  Google Scholar 

  39. Wong CP, Morita H. 1.08-Bacterial type III polyketide synthases. Chem Bio. 2020;1:250–65. https://doi.org/10.1016/B978-0-12-409547-2.14640-2.

    Article  CAS  Google Scholar 

  40. Clara B, Paul V, Denis P, Stéphanie M, Hélène VR, Rémy B. Efficacy of phloroglucinol for the treatment of pain of gynaecologic or obstetrical origin: a systematic review of literature of randomised controlled trials. Eur J ClinPharmacol. 2020;76:541–8. https://doi.org/10.1007/S00228-019-02745-7.

    Article  Google Scholar 

  41. • Yang EJ, Ahn S, Ryu J, Choi MS, Choi S, Chong YH, Hyun JW, Chang MJ, Kim HS. Phloroglucinol attenuates the cognitive deficits of the 5XFAD mouse model of Alzheimer’s disease. PLoS ONE. 2015;10:1–20. https://doi.org/10.1371/journal.pone.0135686. This study demonstrated that phloroglucinol showed promising effect in the treatment of Alzhiemer’s disease by potentially slowing disease progression through its antioxidant properties, mitigating cognitive impairments. It safeguards dendritic spine density and synaptic proteins, indicating its protective impact rather than direct influence on Aβ formation or breakdown.

    Article  CAS  Google Scholar 

  42. • Yang EJ, Mahmood U, Kim H, Choi M, Choi Y, Lee JP, Cho JY, Hyun JW, Kim YS, Chang MJ, Kim HS. Phloroglucinol ameliorates cognitive impairments by reducing the amyloid β peptide burden and pro-inflammatory cytokines in the hippocampus of 5XFAD mice. Free Rad Bio Med. 2018;126:221–34. https://doi.org/10.1016/J.FREERADBIOMED.2018.08.016. This study revealed that administering phloroglucinol orally for two months alleviated neuropathological features and behavioral phenotypes in the 5XFAD mouse model. This effect was achieved through mechanisms involving anti-inflammatory actions and reduction of amyloid β peptide levels.

    Article  CAS  Google Scholar 

  43. Duarte MO, Lunardelli S. Phloroglucinol derivatives present an antidepressant-like effect in the mice tail suspension test (TST). Nat Prod Commun. 2014;9:671–4. https://doi.org/10.1177/1934578X1400900522.

    Article  CAS  PubMed  Google Scholar 

  44. Zonoli P. Role of hyperforin in the pharmacological activities of St. John’s Wort CNS Drugs Rev. 2006;10:203–18. https://doi.org/10.1111/j.1527-3458.2004.tb00022.x.

    Article  Google Scholar 

  45. So JM, Cho JE. Phloroglucinol attenuates free radical-induced oxidative stress. Prev Nutr Food Sci. 2014;19:129–35.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Prakash S, Somiya G, Elavarasan N, Subashini K, Kanaga S, Dhandapani R, Sivanandam M, Kumaradhas P, Thirunavukkarasu C, Sujatha V. Synthesis and characterization of novel bioactive azo compounds fused with benzothiazole and their versatile biological applications. J Mol Struct. 2021;1224:129016. https://doi.org/10.1016/J.MOLSTRUC.2020.129016.

    Article  CAS  Google Scholar 

  47. Daus M, Wunnoo S, Voravuthikunchai SP, Saithong S. Phloroglucinol–meroterpenoids from the leaves of Eucalyptus camaldulensis Dehnh. Phytochem. 2022;200:113179. https://doi.org/10.1016/j.phytochem.2022.113179.

    Article  CAS  Google Scholar 

  48. Hakim MM, Patel IC. A review on phytoconstituents of marine brown algae. Futur J Pharm Sci. 2020;6:129. https://doi.org/10.1186/s43094-020-00147-6.

    Article  Google Scholar 

  49. Liu F, Wu Y, Li NP, Liu JW, Wang L, Ye WC. Front cover: chiral isolation and absolute configuration of (+)- and (−)-Xanchryones F and G from Xanthostemon chrysanthus. Chem Biodiversity. 2020;17:e190068. https://doi.org/10.1002/cbdv.201900723.

    Article  Google Scholar 

  50. Bruna BM, Zibrandtsen JF, Gunbilig D. Quantification and localization of formylated phloroglucinol compounds (FPCs) in Eucalyptus species. Front Plant Sci. 2019;10:214–20. https://doi.org/10.3389/fpls.2019.00186.

    Article  Google Scholar 

  51. Eschler BM, Pass DM, Willis R, Foley WJ. Distribution of foliar formylated phloroglucinol derivatives amongst Eucalyptus species. BiochemSyst Ecol. 2000;28:813–24. https://doi.org/10.1016/S0305-1978(99)00123-4.

    Article  CAS  Google Scholar 

  52. Hogan CM (2008) Coastal wood fern (Dryopteris arguta) http://www.globaltwitcher.com/artspec_information.asp?thingid=88976 Accessed 6.9.22

  53. Na MK, Jang JP, Min BS, Lee SJ, Lee MS, Kim BY, Oh WK, Ahn JS. Fatty acid synthase inhibitory activity of acylphloroglucinols isolated from Dryopteriscrassirhizoma. Bioorg Med Chem Lett. 2006;16:4738–42. https://doi.org/10.1016/j.bmcl.2006.07.018.

    Article  CAS  PubMed  Google Scholar 

  54. Kang KA, Zhang R, Chae S, Lee SJ, Kim J, Kim J, Jeong J, Lee J, Shin T, Lee NH, Hyun JW. Phloroglucinol (1,3,5-trihydroxybenzene) protects against ionizing radiation-induced cell damage through inhibition of oxidative stress in vitro and in vivo. Chemico-BiolInterac. 2010;185:215–26. https://doi.org/10.1016/J.CBI.2010.02.031.

    Article  CAS  Google Scholar 

  55. Okada Y, Ishimaru A, Suzuki R, Okuyama T. A new phloroglucinol derivative from the brown alga Eisenia bicyclis: potential for the effective treatment of diabetic complications. J Nat Prod. 2004;67:103–5. https://doi.org/10.1021/np030323j.

    Article  CAS  PubMed  Google Scholar 

  56. Kennedy J (2020) What are brown algae https://www.thoughtco.com/brown-algae-phaeophyta-2291972 Accessed 8.7.23

  57. Oh YS, Lee IK, Boo SM. An annotated account of Korean economic seaweeds for food, medical and industrial uses. Kor J Phycol. 1990;5:57–71.

    Google Scholar 

  58. Ragan MA, Craigie JS. Physodes and the phenolic compounds of brown algae. Isolation and characterization of phloroglucinol polymers from Fucusvesiculosus (L). Can J Biochem. 1976;54:66–73. https://doi.org/10.1139/O76-011.

    Article  CAS  PubMed  Google Scholar 

  59. Blackman AJ, Rogers GI, Volkman JK. Phloroglucinol derivatives from three Australian marine algae of the genus Zonaria. JNat Prod. 1998;51:158–60. https://doi.org/10.1021/np50055a027.

    Article  Google Scholar 

  60. Achkar J, Xian M, Zhao H, Frost JW. Biosynthesis of phloroglucinol. J Am Chem Soc. 2005;127:5332–3. https://doi.org/10.1021/ja042340g.

    Article  CAS  PubMed  Google Scholar 

  61. Liu X, Liu J, Lei D, Zhao GR. Modular metabolic engineering for production of phloretic acid, phloretin and phlorizin in Escherichia coli. Chem Eng Sci. 2022;247:11693.

    Article  Google Scholar 

  62. National Center for Biotechnology Information (2023) PubChem compound summary for CID 359, Phloroglucinol Pubchem https://pubchem.ncbi.nlm.nih.gov/compound/Phloroglucinol Accessed 09.08.2023

  63. Clarke HT, Hartman WW. Phloroglucinol. Org Synth. 1929;9:74. https://doi.org/10.15227/orgsyn.009.0074.

    Article  CAS  Google Scholar 

  64. Kanan K, Jain SK. Oxidative stress and apoptosis. Pathophysiol. 2000;53:153–63.

    Article  Google Scholar 

  65. Ashok A, Andrabi SS, Mansoor S, Kuang Y, Kwon BK, Labhasetwar V. Antioxidant therapy in oxidative stress-induced neurodegenerative diseases: role of nanoparticle-based drug delivery systems in clinical translation. Antioxid. 2022;11:408. https://doi.org/10.3390/antiox1102040.

    Article  CAS  Google Scholar 

  66. Larson R. Phenolic and enolic antioxidants. Naturally occurring antioxidants New York: Lewis publishers; 1997. p. 83–7.

    Google Scholar 

  67. Kang KA, Lee KH, Chae S, Zhang R, Jung MS, Ham YM, Baik JS, Lee NH, Hyun JW. Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation. J Cell Biochem. 2006;97:609–20. https://doi.org/10.1002/JCB.20668.

    Article  CAS  PubMed  Google Scholar 

  68. • Kim HS, Lee K, Kang KA, Lee NH, Hyun JW, Kim HS. Phloroglucinol exerts protective effects against oxidative stress-induced cell damage in SH-SY5Y cells. J Pharmacol Sci. 2012;119:86–192. https://doi.org/10.1254/JPHS.12056FP. The study implies that phloroglucinol protects SH-SY5Y cells from oxidative stress-induced damage by decreasing levels of 8-isoprostane, protein carbonylation, and 8-hydroxy deoxyguanine caused by hydrogen peroxide.

    Article  Google Scholar 

  69. Park C, Cha HJ, Hong SH, Kim GY, Kim S, Kim HS, Kim BW, Jeon YJ, Choi YH. Protective effect of phloroglucinol on oxidative stress-induced DNA damage and apoptosis through activation of the Nrf2/HO-1 signaling pathway in HaCaT human keratinocytes. Mar Drugs. 2019;17:2334. https://doi.org/10.3390/MD17040225.

    Article  Google Scholar 

  70. Dugger BN, Dickson DW. Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol. 2017;9:126–40. https://doi.org/10.1101/CSHPERSPECT.A028035.

    Article  Google Scholar 

  71. Palop JJ, Mucke L. Amyloid-beta-induced neuronal dysfunction in Alzheimer’s disease: from synapses. Nat Neurosci. 2010;13:812–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Dickson DW. The pathogenesis of senile plaques. J Neuropathol Exp Neurol. 1997;56:321–39. https://doi.org/10.1097/00005072-199704000-00001.

    Article  CAS  PubMed  Google Scholar 

  73. Wallace L, Theou O, Rockwood K, Andrew MK. Relationship between frailty and Alzheimer’s disease biomarkers: a scoping review. Alzheimers Dement. 2018;10:394–401. https://doi.org/10.1016/j.dadm.2018.05.002.

    Article  Google Scholar 

  74. Hyman BT, Trojanowski JQ. Editorial on consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan institute working group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuro pathol Exp Neurol. 1997;56:1095–7. https://doi.org/10.1097/00005072-199710000-00002.

    Article  CAS  Google Scholar 

  75. Mattson MP. Cellular actions of β-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev. 1997;77:1081–132. https://doi.org/10.1152/PHYSREV.1997.77.4.1081.

    Article  CAS  PubMed  Google Scholar 

  76. Matsuoka Y, Picciano M, Francois J, Duff K. Fibrillar β-amyloid evokes oxidative damage in a transgenic mouse model of Alzheimer’s disease. Neurosci. 2001;104:609–13. https://doi.org/10.1016/S0306-4522(01)00115-4.

    Article  CAS  Google Scholar 

  77. Behl C, Davis J, Lesley R, Schubert D. Hydrogen peroxide mediates amyloid β protein toxicity. Cell. 1994;77:817–27.

    Article  CAS  PubMed  Google Scholar 

  78. Gella A, Durany N. Oxidative stress in Alzheimer disease. Cell AdhMigr. 2009;3:88–93. https://doi.org/10.4161/CAM.3.1.7402.

    Article  Google Scholar 

  79. Yang EJ, Kim H, Kim HS, Chang MJ. Phloroglucinol attenuates oligomeric amyloid beta peptide1-42-induced astrocytic activation by reducing oxidative stress. J PharmacolSci. 2021;145:308–12. https://doi.org/10.1016/J.JPHS.2021.01.008.

    Article  CAS  Google Scholar 

  80. Zigmond MJ, Burke RE. Pathophysiology of Parkinson’s disease. Neuropsychopharmacology: Fifth Gener Progress. 2017;1781–1793.

  81. Jang BG, Choi B, Kim S, Lee DS, Lee J, Koh YH, Jo SA, Kim JE, Kang TC, Kim MJ. 2,4-diacetylphloroglucinol reduces beta-amyloid production and secretion by regulating ADAM10 and intracellular trafficking in cellular and animal models of alzheimer’s disease. Cells. 2022;11:2585. https://doi.org/10.3390/cells11162585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ryu J, Zhang R, Hong BH, Yang EJ, Kang KA, Choi M, Kim KC, Noh SJ, Kim HS, Lee NH, Hyun JW, Kim HS. Phloroglucinol attenuates motor functional deficits in an animal model of Parkinson’s disease by enhancing Nrf2 activity. PLoS One. 2013;8:432. https://doi.org/10.1371/JOURNAL.PONE.0071178.

    Article  Google Scholar 

  83. • Wang YD, Bao XQ, Xu S, Yu WW, Cao SN, Hu JP, Li Y, Wang XL, Zhang D, Yu SS. A novel Parkinson’s disease drug candidate with potent anti-neuroinflammatory effects through the Src signaling pathway. J Med Chem. 2016;59:9062–79. https://doi.org/10.1021/ACS.JMEDCHEM.6B00976. The study showed that phloroglucinol protected against synaptic loss in 6-OHDA-lesioned rats’ midbrain, evidenced by enhanced synaptophysin levels. In SH-SY5Y cultures, phloroglucinol reduced 6-OHDA cytotoxicity, diminishing ROS, lipid peroxidation, protein carbonylation, and 8-hydroxyguanine. Phloroglucinol also restored reduced nuclear Nrf2 levels and antioxidant enzyme activity induced by 6-OHDA.

    Article  CAS  PubMed  Google Scholar 

  84. Stuart A (2020) Brain and nervous system: Huntington’s disease. WebMD LCC. https://www.webmd.com/brain/hungtingtons-disease-causes-symptoms-treatment Accessed 12.05.2023

  85. Kumar V, Abbas A, Aster J. Robbins Basic Pathology E-Book. Elsevier; 2017. p. 133–42.

    Google Scholar 

  86. Purves D, Augustine G, Fitzpatrick D, Hall W, Lamantia A. White. Neuroscience 5th Edition - PMC Yale J Biol Med. 2013;86:113–4.

    Google Scholar 

  87. Dayalu P, Albin RL. Huntington disease: pathogenesis and treatment. Neurol Clin. 2015;33:101–14. https://doi.org/10.1016/J.NCL.2014.09.003.

    Article  PubMed  Google Scholar 

  88. Vonsattel JPG, DiFiglia M. Huntington disease. J Neuropathol Exp Neurol. 1998;5:369–84. https://doi.org/10.1097/00005072-199805000-00001.

    Article  Google Scholar 

  89. Kremer HPH, Roos RAC, Dingjan G, Marani E, Bots AM. Atrophy of the hypothalamic lateral tuberal nucleus in Huntington’s disease. J Neuropathol Exp Neurol. 1990;49:371–82. https://doi.org/10.1097/00005072-199007000-00002.

    Article  CAS  PubMed  Google Scholar 

  90. Kassubek J, Landwehrmeyer GB, Ecker D, Juengling FD, Muche R, Schuller S, Weindl A, Peinemann A. Global cerebral atrophy in early stages of Huntington’s disease: quantitative MRI study. Neuro Report. 2007;15:363–5. https://doi.org/10.1097/00001756-200402090-00030.

    Article  Google Scholar 

  91. Heinsen H, Rüb U, Gangnus D, Jungkunz G, Bauer M, Ulmar G, Bethke B, Schüler M, Böcker F, Eisenmenger W, Götz M, Strik M. Nerve cell loss in the thalamic centromedian-parafascicular complex in patients with Huntington’s disease. Acta Neuropathol. 1996;91:161–8. https://doi.org/10.1007/S004010050408.

    Article  CAS  PubMed  Google Scholar 

  92. Petersén Å, Chase K, Puschban Z, DiFiglia M, Brundin P, Aronin N. Maintenance of susceptibility to neurodegeneration following intrastriatal injections of quinolinic acid in a new transgenic mouse model of Huntington’s disease. Exp Neurol. 2002;175:297–300. https://doi.org/10.1006/EXNR.2002.7885.

    Article  PubMed  Google Scholar 

  93. Arenas J, Campos Y, Ribacoba R, Martín MA, Rubio JC, Ablanedo P, Cabello A. Complex I defect in muscle from patients with Huntington’s disease. AnnNeurol. 1998;43:397–400. https://doi.org/10.1002/ANA.410430321.

    Article  CAS  Google Scholar 

  94. Rubinsztein D, Leggo J, Coles R, Almqvist E, Biancalana V, Cassiman JJ, Cothai K, Connarty M, Craufoe D, Curtis A, Curtis D, Davidson M, Differ A, Dode CD, Dodge A, Frontali M, Ranen N, Stine O. Phenotypic characterization of individuals with 30–40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and normal elderly individuals with 36–39 repeats. Am J Hum Genet. 1996;59:16–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Brinkman RR, Mezei MM, Theilmann J, Almqvist E, Hayden MR. The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size. Am J Hum Genet. 1997;60:1202–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Xie Y, Lu J, Yang T, Chen C, Bao Y, Jiang L, Wei H, Wu X, Zhao L, He S, Lin D, Liu F, Liu H, Yan X, Cui W. Phloroglucinol, a clinical-used antispasmodic, inhibits amyloid aggregation and degrades the pre-formed amyloid proteins. Int J BiolMacromo. 2022;213:675–89. https://doi.org/10.1016/J.IJBIOMAC.2022.06.008.

    Article  CAS  Google Scholar 

  97. • Melinosky C (2021) Amyotrophic lateral sclerosis (ALS): symptoms, causes, types https://www.webmd.com/brain/understanding-als-basics Accessed 8.9.22 The study suggested that phloroglucinol possesses the ability to degrade pre-formed amyloid aggregates, to inhibit the seeding during amyloid aggregation, and to reduce the neurotoxicity, indicating the reposition possibility of phloroglucinol as a novel drug for treating neurodegenerative disorders.

  98. Kurtzke JF. Epidemiology of amyotrophic lateral sclerosis. Adv Neurol. 1982;36:281–302. https://doi.org/10.52667/2712-9179-2022-2-1-57-66.

    Article  CAS  PubMed  Google Scholar 

  99. Jokelainen M. Amyotrophic lateral sclerosis in Finland: II: clinical characteristics. Acta Neurol Scand. 1977;56:194–204. https://doi.org/10.1111/J.1600-0404.1977.TB01425.X.

    Article  CAS  PubMed  Google Scholar 

  100. Van EMA, Hardiman O, Chio A, Al-Chalabi A, Pasterkamp RJ, Veldink JH, Van den Berg LH. Amyotrophic lateral sclerosis. Lancet. 2017;390:2084–98. https://doi.org/10.1016/S0140-6736(17)31287-4.

    Article  Google Scholar 

  101. Chiò A, Mora G, Lauria G. Pain in amyotrophic lateral sclerosis. Lancet Neurol. 2017;16:144–57. https://doi.org/10.1016/S1474-4422(16)30358-1.

    Article  PubMed  Google Scholar 

  102. Hilton JB, White AR, Crouch PJ. Metal-deficient SOD1 in amyotrophic lateral sclerosis. J Mol Med. 2015;93:481–7. https://doi.org/10.1007/s00109-015-1273-3.

    Article  CAS  PubMed  Google Scholar 

  103. Morgan S, Orrell RW. Pathogenesis of amyotrophic lateral sclerosis. Br Med Bull. 2016;119:87–97. https://doi.org/10.1093/BMB/LDW026.

    Article  CAS  PubMed  Google Scholar 

  104. Wingo TS, Cutler DJ, Yarab N, Kelly CM, Glass JD. The heritability of amyotrophic lateral sclerosis in a clinically ascertained United States research registry. PLoS One. 2011;6:e27985. https://doi.org/10.1371/journal.pone.0027985.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, Burrell JR, Zoing MC. Amyotrophic lateral sclerosis. Lancet. 2011;377:942–55. https://doi.org/10.1016/s0140-6736(10)61156-7.

    Article  CAS  PubMed  Google Scholar 

  106. Couratier P, Corcia P, Lautrette G, Nicol M, Marin B. ALS and frontotemporal dementia belong to a common disease spectrum. Rev Neurol. 2017;173:273–9. https://doi.org/10.1016/j.neurol.2017.04.001.

    Article  CAS  PubMed  Google Scholar 

  107. Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017;377:162–72. https://doi.org/10.1056/NEJMra1603471.

    Article  CAS  PubMed  Google Scholar 

  108. Cunha-Oliveira T, Montezinho L, Mendes C, Firuzi O, Saso L, Oliveira PJ, Silva FSG. Oxidative stress in amyotrophic lateral sclerosis. Pathophysio Opp PharmacolInterven. 2020. https://doi.org/10.1155/2020/5021694.

    Article  Google Scholar 

  109. Hoffmann LF, Martins A, Majolo F, Contini V, Laufer S, Goettert MI. Neural regeneration research model to be explored: SH-SY5Y human neuroblastoma cells. Neural Regen Res. 2023;18(6):1265–6. https://doi.org/10.4103/1673-5374.358621.

    Article  CAS  PubMed  Google Scholar 

  110. Peng Y, Chu S, Yang Y, Zhang Z, Pang Z, Chen N. Neuroinflammatory in vitro cell culture models and the potential applications for neurological disorders. Front Pharmacol. 2021;12:671734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Laudati G, Mascolo L, Guida N, Sirabella R, Pizzorusso V, Bruzzaniti S, Serani A, Renzo GD, Canzoniero LMT, Formisano L. Resveratrol treatment reduces the vulnerability of SH-SY5Y cells and cortical neurons overexpressing SOD1-G93A to Thimerosal toxicity through SIRT1/DREAM/PDYN pathway. Neurotoxicology. 2019;71:6–15. https://doi.org/10.1016/j.neuro.2018.11.009.

    Article  CAS  PubMed  Google Scholar 

  112. Anonymous. Final report on the safety assessment of phloroglucinol. J Am Coll Toxicol. 1995;14:468–75.https://doi.org/10.3109/10915819509010306

  113. Harwanto D, Negara BF, Tirtawijaya G, Meinita MDN, Choi JS. Evaluation of toxicity of crude phlorotannins and phloroglucinol using different model organisms. Toxins. 2022;14:312. https://doi.org/10.3390/TOXINS14050312/S1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Anonymous (2023) Registration dossier, CAS number: 108–73–6. European Chemical Agency. https://echa.europa.eu/registration-dossier/-/registered-dossier/23677/7/1 Accessed 15.07.2023

  115. Corvino A, Magli E, Minale M. Phloroglucinol-derived medications are effective in reducing pain and spasms of urinary and biliary tracts: results of phase 3 multicentre, open-label, randomized, comparative studies of clinical effectiveness and safety. Adv Ther. 2023;40:619–40. https://doi.org/10.1007/s12325-022-02347-3.

    Article  CAS  PubMed  Google Scholar 

  116. Anonymous (2023a) Uses of phloroglucinol. Vinmac Health Care System. https://www.vinmec.com/en/pharmaceutical-information/use-medicines-safely/uses-of-phloroglucinol/ Accessed 09.07.2023

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Acknowledgements

The author wishes to acknowledge the Bina Chowdhury Central Library, Girijananda Chowdhury University, Assam (Guwahati, India), for providing access to internet facilities and electronic database information. All the images were generated using Biorender 2023 software which is also deeply acknowledged.

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  1. Department of Pharmacology, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India

    Nayana Bhuyan & Shatabdi Ghose

  2. Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, India

    Nikhil Biswas

  3. Advanced Drug Delivery Laboratory, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, India

    Jaheer Ali Sultan

  4. Phytochemical Research Laboratory, Department of Pharmacognosy, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, India

    Damiki Laloo

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NBU and JS have collected the required information through a literature review. NBU conceived, designed, and drafted the manuscript. NB critically revised the manuscript for technical, typological, and grammatical errors. DL and SG supervised and conceptualized the work, proof editing, and critical revision of the manuscript. All the authors have read, proof checked, and approved the final version of the manuscript.

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Bhuyan, N., Ghose, S., Biswas, N. et al. From Bench to Bedside: Unveiling the Effects of Phloroglucinol as a Promising Neuroprotective Agent in the Battle Against Neurodegenerative Disorders. Curr Behav Neurosci Rep (2024). https://doi.org/10.1007/s40473-024-00271-0

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