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image of Glucagon-like Peptide-1 Boosts Plumbagin’s Neuroprotection Against Rotenone-Induced Motor Deficits

Abstract

Introduction

Parkinson's disease (PD), a condition that involves neural degeneration, develops due to dopaminergic neuronal death in the substantia nigra pars compacta, resulting in reduced striatal dopamine levels. This shortage causes problems with movement and thinking. The neurodefensive response of GLP-1 is especially important in PD. Assessments have demonstrated the neuroprotective advantages of activating GLP-1 receptors in distinct models of PD, resulting in enhancements in motor as well as non-motor behaviour. These characteristics suggest that GLP-1 signalling could be a promising target for PD treatment. Moreover, plumbagin is the primary active component of Plumbago zeylanica L., a medicinal herb that is clinically used in China. Also, plumbagin is reported to have significant neuroprotective efficacy.

Method

In this study, male rats received rotenone (1.5 mg/kg; subcutaneously), followed by plumbagin (20 mg/kg; p.o.). The rats’ motor abilities were assessed using the actophotometer, beam walk, rotarod, gait analysis, open field, grip strength, as well as bar catalepsy evaluation. In addition, the levels of dopamine, RAGE, and GLP-1 were measured.

Results

Plumbagin improved movement issues caused by rotenone, boosted dopamine and GLP-1 levels, as well as lowered RAGE levels in the brains of rats.

Discussion

The study highlights plumbagin’s potential in treating PD by improving motor function, increasing dopamine and GLP-1 levels, and reducing RAGE levels in a rotenone-induced rat model. These findings suggest that plumbagin may offer neuroprotective effects through GLP-1 pathway activation, making it a promising candidate for future PD therapies.

Conclusion

These outcomes imply that agents that activate GLP-1, such as plumbagin, present a promising strategy for creating treatments to safeguard against rotenone-induced motor disorders.

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2025-10-23
2026-01-29

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References

  1. Goyal A. Solanki K. Verma A. Luteolin: Nature’s promising warrior against Alzheimer’s and Parkinson’s disease. J. Biochem. Mol. Toxicol. 2024 38 1 23619 10.1002/jbt.23619 38091364
    [Google Scholar]
  2. Verma A. Chaudhary S. Solanki K. Goyal A. Yadav H.N. Exendin-4: A potential therapeutic strategy for Alzheimer’s disease and Parkinson’s disease. Chem. Biol. Drug Des. 2024 103 1 14426 10.1111/cbdd.14426 38230775
    [Google Scholar]
  3. Poewe W. Seppi K. Tanner C.M. Halliday G.M. Brundin P. Volkmann J. Schrag A.E. Lang A.E. Parkinson disease. Nat. Rev. Dis. Primers 2017 3 1 17013 10.1038/nrdp.2017.13 28332488
    [Google Scholar]
  4. Hald A. Lotharius J. Oxidative stress and inflammation in Parkinson’s disease: Is there a causal link? Exp. Neurol. 2005 193 2 279 290 10.1016/j.expneurol.2005.01.013 15869932
    [Google Scholar]
  5. Gasparotto J. Somensi N. Girardi C.S. Bittencourt R.R. de Oliveira L.M. Hoefel L.P. Scheibel I.M. Peixoto D.O. Moreira J.C.F. Outeiro T.F. Gelain D.P. Is it all the RAGE? Defining the role of the receptor for advanced glycation end products in Parkinson’s disease. J. Neurochem. 2024 168 8 1608 1624 10.1111/jnc.15890 37381043
    [Google Scholar]
  6. Goyal A. Agrawal A. Dubey N. Verma A. High mobility group box 1 protein: A plausible therapeutic molecular target in Parkinson’s disease. Curr. Pharm. Biotechnol. 2024 25 8 937 943 10.2174/1389201025666230905092218 37670710
    [Google Scholar]
  7. Ben-Shlomo Y. Darweesh S. Llibre-Guerra J. Marras C. San Luciano M. Tanner C. The epidemiology of Parkinson’s disease. Lancet 2024 403 10423 283 292 10.1016/S0140‑6736(23)01419‑8 38245248
    [Google Scholar]
  8. Armstrong M.J. Okun M.S. Diagnosis and treatment of Parkinson disease: A review. JAMA 2020 323 6 548 560 10.1001/jama.2019.22360 32044947
    [Google Scholar]
  9. Holst J.J. Burcelin R. Nathanson E. Neuroprotective properties of GLP-1: Theoretical and practical applications. Curr. Med. Res. Opin. 2011 27 3 547 558 10.1185/03007995.2010.549466 21222567
    [Google Scholar]
  10. Katsurada K. Yada T. Neural effects of gut- and brain-derived glucagon-like peptide-1 and its receptor agonist. J. Diabetes Investig. 2016 7 Suppl 1 64 69
    [Google Scholar]
  11. Pyke C. Heller R.S. Kirk R.K. Ørskov C. Reedtz-Runge S. Kaastrup P. Hvelplund A. Bardram L. Calatayud D. Knudsen L.B. GLP-1 receptor localization in monkey and human tissue: Novel distribution revealed with extensively validated monoclonal antibody. Endocrinology 2014 155 4 1280 1290 10.1210/en.2013‑1934 24467746
    [Google Scholar]
  12. Erbil D. Eren C.Y. Demirel C. Küçüker M.U. Solaroğlu I. Eser H.Y. GLP-1’s role in neuroprotection: A systematic review. Brain Inj. 2019 33 6 734 819 10.1080/02699052.2019.1587000 30938196
    [Google Scholar]
  13. Standaert D.G. GLP-1, Parkinson’s disease, and neuroprotection. N. Engl. J. Med. 2024 390 13 1233 1234 10.1056/NEJMe2401743 38598580
    [Google Scholar]
  14. Kalinderi K. Papaliagkas V. Fidani L. GLP-1 receptor agonists: A new treatment in Parkinson’s disease. Int. J. Mol. Sci. 2024 25 7 3812 10.3390/ijms25073812 38612620
    [Google Scholar]
  15. Yadav A.M. Bagade M.M. Ghumnani S. Raman S. Saha B. Kubatzky K.F. Ashma R. The phytochemical plumbagin reciprocally modulates osteoblasts and osteoclasts. Biol. Chem. 2022 403 2 211 229 10.1515/hsz‑2021‑0290 34882360
    [Google Scholar]
  16. Panichayupakaranant P. Ahmad M.I. Plumbagin and its role in chronic diseases. Adv. Exp. Med. Biol. 2016 929 229 246 10.1007/978‑3‑319‑41342‑6_10 27771927
    [Google Scholar]
  17. Sukkasem N. Chatuphonprasert W. Tatiyaaphiradee N. Jarukamjorn K. Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice. J. Intercult. Ethnopharmacol. 2016 5 2 137 145 10.5455/jice.20160301094913 27104034
    [Google Scholar]
  18. Kuan-hong W. Bai-zhou L. Plumbagin protects against hydrogen peroxide-induced neurotoxicity by modulating NF-κB and Nrf-2. Arch. Med. Sci. 2018 14 5 1112 1118 10.5114/aoms.2016.64768 30154895
    [Google Scholar]
  19. Wang S. Zhang Z. Zhao S. Plumbagin inhibits amyloid-β-induced neurotoxicity. Neuroreport 2018 29 15 1269 1274 10.1097/WNR.0000000000001103 30095583
    [Google Scholar]
  20. Yuan J.H. Pan F. Chen J. Chen C.E. Xie D.P. Jiang X.Z. Guo S.J. Zhou J. Neuroprotection by plumbagin involves BDNF-TrkB-PI3K/Akt and ERK1/2/JNK pathways in isoflurane-induced neonatal rats. J. Pharm. Pharmacol. 2017 69 7 896 906 10.1111/jphp.12681 28464236
    [Google Scholar]
  21. Kumar Arora M. Ratra A. Asdaq S.M.B. Alshamrani A.A. Alsalman A.J. Kamal M. Tomar R. Sahoo J. Ashok J. Imran M. Plumbagin alleviates intracerebroventricular-quinolinic acid induced depression-like behavior and memory deficits in wistar rats. Molecules 2022 27 6 1834 10.3390/molecules27061834 35335195
    [Google Scholar]
  22. Su Y. Li M. Wang Q. Xu X. Qin P. Huang H. Zhang Y. Zhou Y. Yan J. Inhibition of the TLR/NF-κB signaling pathway and improvement of autophagy mediates neuroprotective effects of plumbagin in Parkinson’s disease. Oxid. Med. Cell Longev. 2022 2022 1 1837278 10.1155/2022/1837278 36589679
    [Google Scholar]
  23. Chen X.J. Zhang J.G. Wu L. Plumbagin inhibits neuronal apoptosis, intimal hyperplasia and also suppresses TNF-α/NF-κB pathway induced inflammation and matrix metalloproteinase-2/9 expression in rat cerebral ischemia. Saudi J. Biol. Sci. 2018 25 6 1033 1039 10.1016/j.sjbs.2017.03.006 30174499
    [Google Scholar]
  24. Son T.G. Camandola S. Arumugam T.V. Cutler R.G. Telljohann R.S. Mughal M.R. Moore T.A. Luo W. Yu Q.S. Johnson D.A. Johnson J.A. Greig N.H. Mattson M.P. Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia. J. Neurochem. 2010 112 5 1316 1326 10.1111/j.1471‑4159.2009.06552.x 20028456
    [Google Scholar]
  25. Arruri V. Komirishetty P. Areti A. Dungavath S.K.N. Kumar A. Nrf2 and NF-κB modulation by Plumbagin attenuates functional, behavioural and biochemical deficits in rat model of neuropathic pain. Pharmacol. Rep. 2017 69 4 625 632 10.1016/j.pharep.2017.02.006 28505604
    [Google Scholar]
  26. Zhang K. Ge Z. Da Y. Wang D. Liu Y. Xue Z. Li Y. Li W. Zhang L. Wang H. Zhang H. Peng M. Hao J. Yao Z. Zhang R. Plumbagin suppresses dendritic cell functions and alleviates experimental autoimmune encephalomyelitis. J. Neuroimmunol. 2014 273 1-2 42 52 10.1016/j.jneuroim.2014.05.014 24953531
    [Google Scholar]
  27. Radad K. Al-Shraim M. Al-Emam A. Wang F. Kranner B. Rausch W.D. Moldzio R. Rotenone: From modelling to implication in Parkinson’s disease. Folia Neuropathol. 2019 57 4 317 326 10.5114/fn.2019.89857 32337944
    [Google Scholar]
  28. Liang W. Yao L. Chen J. Chen Z. Wu X. Huang X. Therapeutic and neuroprotective effects of Bushen Jianpi decoction on a rotenone-induced rat model of Parkinson’s disease. Evid. Based Complement. Alternat. Med. 2022 2022 1 15 10.1155/2022/9191284 36437828
    [Google Scholar]
  29. Cannon J.R. Tapias V. Na H.M. Honick A.S. Drolet R.E. Greenamyre J.T. A highly reproducible rotenone model of Parkinson’s disease. Neurobiol. Dis. 2009 34 2 279 290 10.1016/j.nbd.2009.01.016 19385059
    [Google Scholar]
  30. Thiffault C. Langston J.W. Di Monte D.A. Increased striatal dopamine turnover following acute administration of rotenone to mice. Brain Res. 2000 885 2 283 288 10.1016/S0006‑8993(00)02960‑7 11102582
    [Google Scholar]
  31. Henderson J.M. Stanic D. Tomas D. Patch J. Horne M.K. Bourke D. Finkelstein D.I. Postural changes after lesions of the substantia nigra pars reticulata in hemiparkinsonian monkeys. Behav. Brain Res. 2005 160 2 267 276 10.1016/j.bbr.2004.12.008 15863223
    [Google Scholar]
  32. Kiasalari Z. Baluchnejadmojarad T. Roghani M. Hypericum perforatum hydroalcoholic extract mitigates motor dysfunction and is neuroprotective in intrastriatal 6-hydroxydopamine rat model of Parkinson’s disease. Cell Mol. Neurobiol. 2016 36 4 521 530 10.1007/s10571‑015‑0230‑6 26119304
    [Google Scholar]
  33. hegab Ahmed O. Mahmoud M. Abdelhamid A. Behavioral evaluation of rotenone model of parkinson’s disease in male wistar rats. Sohag. Med. J. 2020 24 2 8 14 10.21608/smj.2020.21596.1089
    [Google Scholar]
  34. Garabadu D. Agrawal N. Naringin exhibits neuroprotection against rotenone-induced neurotoxicity in experimental rodents. Neuromolecular. Med. 2020 22 2 314 330 10.1007/s12017‑019‑08590‑2 31916219
    [Google Scholar]
  35. Verma A. Goyal A. Reformative effect of daidzein on motor dysfunction following rotenone injection in ovariectomized rats. Rev. Bras. Farmacogn. 2022 32 4 563 574 10.1007/s43450‑022‑00277‑3
    [Google Scholar]
  36. Knani L. Venditti M. Rouis H. Minucci S. Messaoudi I. Effects of dopaminergic neuron degeneration on osteocyte apoptosis and osteogenic markers in 6-OHDA male rat model of Parkinson’s disease. Bone 2025 190 117271 10.1016/j.bone.2024.117271 39369834
    [Google Scholar]
  37. Kumar P. Kalonia H. Kumar A. Novel protective mechanisms of antidepressants against 3-nitropropionic acid induced Huntington’s-like symptoms: A comparative study. J. Psychopharmacol. 2011 25 10 1399 1411 10.1177/0269881110364269 20305041
    [Google Scholar]
  38. Agrawal S.S. Gullaiya S. Dubey V. Singh V. Kumar A. Nagar A. Tiwari P. Neurodegenerative shielding by curcumin and its derivatives on brain lesions induced by 6-OHDA model of Parkinson’s disease in albino wistar rats. Cardiovasc. Psychiatry Neurol. 2012 2012 1 8 10.1155/2012/942981 22928089
    [Google Scholar]
  39. Raj K. Gupta G.D. Singh S. L-Theanine ameliorates motor deficit, mitochondrial dysfunction, and neurodegeneration against chronic tramadol induced rats model of Parkinson’s disease. Drug Chem. Toxicol. 2022 45 5 2097 2108 10.1080/01480545.2021.1907909 34210222
    [Google Scholar]
  40. Ferro M.M. Bellissimo M.I. Anselmo-Franci J.A. Angellucci M.E.M. Canteras N.S. Da Cunha C. Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson’s disease: Histological, neurochemical, motor and memory alterations. J. Neurosci. Methods 2005 148 1 78 87 10.1016/j.jneumeth.2005.04.005 15939479
    [Google Scholar]
  41. Karl T. Duffy L. Obrien E. Matsumoto I. Dedova I. Behavioural effects of chronic haloperidol and risperidone treatment in rats. Behav. Brain Res. 2006 171 2 286 294 10.1016/j.bbr.2006.04.004 16697060
    [Google Scholar]
  42. Guo L. Zhang Y. Li Q. Spectrophotometric determination of dopamine hydrochloride in pharmaceutical, banana, urine and serum samples by potassium ferricyanide-Fe(III). Anal. Sci. 2009 25 12 1451 1455 10.2116/analsci.25.1451 20009333
    [Google Scholar]
  43. Gopi C. Sastry V.G. Dhanaraju M.D. Effect of novel phenothiazine derivatives on brain dopamine in wistar rats. Beni. Suef Univ. J. Basic Appl. Sci. 2019 8 1 9
    [Google Scholar]
  44. Famusiwa C.D. Josiah S.S. Saliu I.O. Fatoki T.H. Umar H.I. Akinmoladun A.C. Taxifolin alleviate metabolic and neurochemical alterations in the hippocampus and cortex of rats with rotenone-induced toxicity: In vivo and in silico insight. Pharmacol. Res. Mod. Chin. Med. 2024 11 100439 10.1016/j.prmcm.2024.100439
    [Google Scholar]
  45. Tilak J.C. Adhikari S. Devasagayam T.P.A. Antioxidant properties of Plumbago zeylanica, an Indian medicinal plant and its active ingredient, plumbagin. Redox Rep. 2004 9 4 219 227 10.1179/135100004225005976 15479566
    [Google Scholar]
  46. Checker R. Sharma D. Sandur S.K. Subrahmanyam G. Krishnan S. Poduval T.B. Sainis K.B. Plumbagin inhibits proliferative and inflammatory responses of T cells independent of ROS generation but by modulating intracellular thiols. J. Cell. Biochem. 2010 110 5 1082 1093 10.1002/jcb.22620 20564204
    [Google Scholar]
  47. Luo Y. Mughal M.R. Ouyang T.G.S.X. Jiang H. Luo W. Yu Q.S. Greig N.H. Mattson M.P. Plumbagin promotes the generation of astrocytes from rat spinal cord neural progenitors via activation of the transcription factor Stat3. J. Neurochem. 2010 115 6 1337 1349 10.1111/j.1471‑4159.2010.06780.x 20456019
    [Google Scholar]
  48. Verma A. Goyal A. Plumbagin’s healing effect on motor impairment in rotenone-toxified rodents. Curr. Neurovasc. Res. 2024 39229982
    [Google Scholar]
  49. Verma A. Goyal A. Beyond insulin: The intriguing role of GLP-1 in Parkinson’s disease. Eur. J. Pharmacol. 2024 982 176936 10.1016/j.ejphar.2024.176936 39182542
    [Google Scholar]
  50. Khadrawy Y.A. Salem A.M. El-Shamy K.A. Ahmed E.K. Fadl N.N. Hosny E.N. Neuroprotective and therapeutic effect of caffeine on the rat model of Parkinson’s disease induced by rotenone. J. Diet. Suppl. 2017 14 5 553 572 10.1080/19390211.2016.1275916 28301304
    [Google Scholar]
  51. Chia S.J. Tan E.K. Chao Y.X. Historical perspective: Models of Parkinson’s disease. Int. J. Mol. Sci. 2020 21 7 2464 10.3390/ijms21072464 32252301
    [Google Scholar]
  52. Saravanan K.S. Sindhu K.M. Senthilkumar K.S. Mohanakumar K.P. l-deprenyl protects against rotenone-induced, oxidative stress-mediated dopaminergic neurodegeneration in rats. Neurochem. Int. 2006 49 1 28 40 10.1016/j.neuint.2005.12.016 16490285
    [Google Scholar]
  53. Abdelsalam R.M. Safar M.M. Neuroprotective effects of vildagliptin in rat rotenone Parkinson’s disease model: Role of RAGE-NFκB and Nrf2-antioxidant signaling pathways. J. Neurochem. 2015 133 5 700 707 10.1111/jnc.13087 25752913
    [Google Scholar]
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Glucagon-like Peptide-1 Boosts Plumbagin’s Neuroprotection Against Rotenone-Induced Motor Deficits
Bentham Science Publishers ; https://doi.org/10.2174/0113892037402724251006011830
/content/journals/cpps/10.2174/0113892037402724251006011830
/content/journals/cpps/10.2174/0113892037402724251006011830
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  • Article Type:     Research Article
Keywords: dopamine ; plumbagin ; GLP-1 ; Plumbago zeylanica ; neuroprotective ; Parkinson

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