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2000
Volume 21, Issue 4
  • ISSN: 1567-2026
  • E-ISSN: 1875-5739

Abstract

Background

Parkinson's disease is an illness marked by a gradual mitigation of dopamine neurons within the substantia nigra, which eventually leads to a deficiency of dopamine that further gives rise to mobility as well as cognitive impairments. Through long-established traditions, a wide array of Traditional Chinese Medicines (TCM) have undergone testing and are employed to avoid neurodegenerative disorders. Plumbagin is the primary active component of a medication called Baihua Dan or L., which is clinically used in China.

Objectives

This study investigated plumbagin-induced alterations in a Parkinson's disease rat model instigated by subcutaneous rotenone injection.

Methods

Male rats were administered subcutaneous injections of rotenone at a dosage of 1.5 mg/kg, followed by the treatment with varying doses of plumbagin (10, 20, and 40 mg/kg) through the oral route. The rats underwent various motor ability tests, including the actophotometer, rotarod, open field, beam walk, gait evaluation, ability to grip, and catalepsy bar tests. Furthermore, the brain dopamine level was then estimated for the extracted tissues. Also, through molecular docking, the binding effectiveness of plumbagin was assessed for human MAO-B. After that, plumbagin was put through 100 ns of molecular dynamic simulations to examine the stability of its conformational binding to the target protein. Furthermore, ADMET tests were used to verify Plumbagin's druggability.

Results

Plumbagin was found to alleviate rotenone-induced motor abnormalities and restore brain dopamine levels. Furthermore, plumbagin showed excellent interactions with MAO-B (monoamine oxidase-B) when compared with selegiline (a standard drug for Parkinson’s disease).

Conclusion

These findings underscore the potential therapeutic efficacy of plumbagin in mitigating behavioural deficits in rotenone-induced rodents. Considering this, plumbagin might be a feasible pharmacological strategy for the control of rotenone-triggered behavioural impairment in rats (), and it might display interesting interactions with MAO-B ().

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2025-05-10
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References

  1. GarabaduD. AgrawalN. SharmaA. SharmaS. Mitochondrial metabolism: A common link between neuroinflammation and neurodegeneration.Behav. Pharmacol.201930864165110.1097/FBP.000000000000050531625975
    [Google Scholar]
  2. GoyalA. AgrawalA. VermaA. DubeyN. The PI3K-AKT pathway: A plausible therapeutic target in Parkinson’s disease.Exp. Mol. Pathol.202312910484610.1016/j.yexmp.2022.10484636436571
    [Google Scholar]
  3. AscherioA. SchwarzschildM.A. The epidemiology of Parkinson’s disease: Risk factors and prevention.Lancet Neurol.201615121257127210.1016/S1474‑4422(16)30230‑727751556
    [Google Scholar]
  4. CrottyG.F. KeavneyJ.L. AlcalayR.N. MarekK. MarshallG.A. RosasH.D. SchwarzschildM.A. Planning for prevention of Parkinson disease: Now is the time.Neurology2022997_Supplement_1Suppl. 11910.1212/WNL.000000000020078936219787
    [Google Scholar]
  5. GarabaduD. AgrawalN. Naringin exhibits neuroprotection against rotenone-induced neurotoxicity in experimental rodents.Neuromolecular Med.202022231433010.1007/s12017‑019‑08590‑231916219
    [Google Scholar]
  6. GoyalA. VermaA. AgrawalA. DubeyN. KumarA. BehlT. Therapeutic implications of crocin in Parkinson’s disease: A review of preclinical research.Chem. Biol. Drug Des.202310161229124010.1111/cbdd.1421036752710
    [Google Scholar]
  7. WuK.J. HungT.W. WangY.S. ChenY.H. BaeE.K. YuS.J. Prosaposin PS18 reduces dopaminergic neurodegeneration in a 6-hydroxydopamine rat model of Parkinson’s disease.Sci. Rep.2023131814810.1038/s41598‑023‑35274‑637208379
    [Google Scholar]
  8. CiliaR. AkpaluA. SarfoF.S. ChamM. AmboniM. CeredaE. FabbriM. AdjeiP. AkassiJ. BonettiA. PezzoliG. The modern pre-levodopa era of Parkinson’s disease: Insights into motor complications from sub-Saharan Africa.Brain2014137102731274210.1093/brain/awu19525034897
    [Google Scholar]
  9. FahnS. OakesD. ShoulsonI. KieburtzK. RudolphA. LangA. OlanowC.W. TannerC. MarekK. Levodopa and the progression of Parkinson’s disease.N. Engl. J. Med.2004351242498250810.1056/NEJMoa03344715590952
    [Google Scholar]
  10. LiangW. YaoL. ChenJ. ChenZ. WuX. HuangX. Therapeutic and neuroprotective effects of Bushen Jianpi decoction on a rotenone-induced rat model of Parkinson’s disease.Evid. Based Complement. Alternat. Med.2022202211510.1155/2022/919128436437828
    [Google Scholar]
  11. IranshahyM. JavadiB. SahebkarA. Protective effects of functional foods against Parkinson’s disease: A narrative review on pharmacology, phytochemistry, and molecular mechanisms.Phytother. Res.20223651952198910.1002/ptr.742535244296
    [Google Scholar]
  12. Jimenez-Del-RioM. Guzman-MartinezC. Velez-PardoC. The effects of polyphenols on survival and locomotor activity in Drosophila melanogaster exposed to iron and paraquat.Neurochem. Res.201035222723810.1007/s11064‑009‑0046‑119701790
    [Google Scholar]
  13. ThakorN. JanathiaB. Plumbagin: A potential candidate for future research and development.Curr. Pharm. Biotechnol.202223151800181210.2174/138920102366621123011314634967293
    [Google Scholar]
  14. VermaA. GoyalA. Unravelling the potent anti-oxidant and anti-inflammatory actions of plumbagin: A review of preclinical discoveries.Pharmacol. Res. Mod. Chin. Med.202327100351
    [Google Scholar]
  15. SunilC. DuraipandiyanV. AgastianP. IgnacimuthuS. Antidiabetic effect of plumbagin isolated from Plumbago zeylanica L. root and its effect on GLUT4 translocation in streptozotocin-induced diabetic rats.Food Chem. Toxicol.201250124356436310.1016/j.fct.2012.08.04622960630
    [Google Scholar]
  16. Kuan-hongW. Bai-zhouL. Plumbagin protects against hydrogen peroxide-induced neurotoxicity by modulating NF-κB and Nrf-2.Arch. Med. Sci.20181451112111810.5114/aoms.2016.6476830154895
    [Google Scholar]
  17. WangS. ZhangZ. ZhaoS. Plumbagin inhibits amyloid-β-induced neurotoxicity.Neuroreport201829151269127410.1097/WNR.000000000000110330095583
    [Google Scholar]
  18. ChenX.J. ZhangJ.G. WuL. 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.20182561033103910.1016/j.sjbs.2017.03.00630174499
    [Google Scholar]
  19. ArruriV. KomirishettyP. AretiA. DungavathS.K.N. KumarA. Nrf2 and NF-κB modulation by Plumbagin attenuates functional, behavioural and biochemical deficits in rat model of neuropathic pain.Pharmacol. Rep.201769462563210.1016/j.pharep.2017.02.00628505604
    [Google Scholar]
  20. ZhangK. GeZ. DaY. WangD. LiuY. XueZ. LiY. LiW. ZhangL. WangH. ZhangH. PengM. HaoJ. YaoZ. ZhangR. Plumbagin suppresses dendritic cell functions and alleviates experimental autoimmune encephalomyelitis.J. Neuroimmunol.20142731-2425210.1016/j.jneuroim.2014.05.01424953531
    [Google Scholar]
  21. SubarajaM. VanisreeA.J. Rotenone causing dysfunctional mitochondria and lysosomes in cerebral ganglions of Lumbricus terrestris degenerate giant fibers and neuromuscular junctions.Chemosphere201615246848010.1016/j.chemosphere.2016.02.13227003369
    [Google Scholar]
  22. VermaA. GoyalA. Reformative effect of daidzein on motor dysfunction following rotenone injection in ovariectomized rats.Rev. Bras. Farmacogn.202232456357410.1007/s43450‑022‑00277‑3
    [Google Scholar]
  23. CannonJ.R. TapiasV. NaH.M. HonickA.S. DroletR.E. GreenamyreJ.T. A highly reproducible rotenone model of Parkinson’s disease.Neurobiol. Dis.200934227929010.1016/j.nbd.2009.01.01619385059
    [Google Scholar]
  24. ThiffaultC. LangstonJ.W. Di MonteD.A. Increased striatal dopamine turnover following acute administration of rotenone to mice.Brain Res.2000885228328810.1016/S0006‑8993(00)02960‑711102582
    [Google Scholar]
  25. LuongT.N. CarlisleH.J. SouthwellA. PattersonP.H. Assessment of motor balance and coordination in mice using the balance beam.J. Vis. Exp.20112376492376-v10.3791/2376‑v21445033
    [Google Scholar]
  26. AllbuttH.N. HendersonJ.M. Use of the narrow beam test in the rat, 6-hydroxydopamine model of Parkinson’s disease.J. Neurosci. Methods2007159219520210.1016/j.jneumeth.2006.07.00616942799
    [Google Scholar]
  27. Van Den BuuseM. VeldhuisH.D. De BoerS. VersteegD.H.G. De JongW. Central 6-OHDA affects both open-field exploratory behaviour and the development of hypertension in SHR.Pharmacol. Biochem. Behav.1986241152110.1016/0091‑3057(86)90037‑73080759
    [Google Scholar]
  28. KuniishiH. IchisakaS. YamamotoM. IkuboN. MatsudaS. FutoraE. HaradaR. IshiharaK. HataY. Early deprivation increases high-leaning behavior, a novel anxiety-like behavior, in the open field test in rats.Neurosci. Res.2017123273510.1016/j.neures.2017.04.01228450152
    [Google Scholar]
  29. RozasG. GuerraM.J. Labandeira-GarcíaJ.L. An automated rotarod method for quantitative drug-free evaluation of overall motor deficits in rat models of parkinsonism.Brain Res. Brain Res. Protoc.199721758410.1016/S1385‑299X(97)00034‑29438075
    [Google Scholar]
  30. FernandezA.M. de la VegaA.G. Torres-AlemanI. Insulin-like growth factor I restores motor coordination in a rat model of cerebellar ataxia.Proc. Natl. Acad. Sci. USA19989531253125810.1073/pnas.95.3.12539448318
    [Google Scholar]
  31. KheradmandA. NayebiA.M. JorjaniM. HaddadiR. Effect of WR-1065 on 6-hydroxydopamine-induced catalepsy and IL-6 level in rats.Iran. J. Basic Med. Sci.201619549049627403255
    [Google Scholar]
  32. GeedM. GarabaduD. AhmadA. KrishnamurthyS. Silibinin pretreatment attenuates biochemical and behavioral changes induced by intrastriatal MPP+ injection in rats.Pharmacol. Biochem. Behav.20141179210310.1016/j.pbb.2013.12.00824345573
    [Google Scholar]
  33. TakeshitaH. YamamotoK. NozatoS. InagakiT. TsuchimochiH. ShiraiM. YamamotoR. ImaizumiY. HongyoK. YokoyamaS. TakedaM. OguroR. TakamiY. ItohN. TakeyaY. SugimotoK. FukadaS. RakugiH. Modified forelimb grip strength test detects aging-associated physiological decline in skeletal muscle function in male mice.Sci. Rep.2017714232310.1038/srep4232328176863
    [Google Scholar]
  34. MeyerO.A. TilsonH.A. ByrdW.C. RileyM.T. A method for the routine assessment of fore- and hindlimb grip strength of rats and mice.Neurobehav. Toxicol.197913233236551317
    [Google Scholar]
  35. ReddyD.S. KulkarniS.K. Possible role of nitric oxide in the nootropic and antiamnesic effects of neurosteroids on aging- and dizocilpine-induced learning impairment.Brain Res.1998799221522910.1016/S0006‑8993(98)00419‑39675286
    [Google Scholar]
  36. KlapdorK. DulferB.G. HammannA. Van der StaayF.J. A low-cost method to analyse footprint patterns.J. Neurosci. Methods1997751495410.1016/S0165‑0270(97)00042‑39262143
    [Google Scholar]
  37. GuoL. ZhangY. LiQ. Spectrophotometric determination of dopamine hydrochloride in pharmaceutical, banana, urine and serum samples by potassium ferricyanide-Fe(III).Anal. Sci.200925121451145510.2116/analsci.25.145120009333
    [Google Scholar]
  38. GopiC. SastryV.G. DhanarajuM.D. Effect of novel phenothiazine derivatives on brain dopamine in Wistar rats.Beni. Suef Univ. J. Basic Appl. Sci.2019819
    [Google Scholar]
  39. KuppusamyA. ArumugamM. GeorgeS. Combining in silico and in vitro approaches to evaluate the acetylcholinesterase inhibitory profile of some commercially available flavonoids in the management of Alzheimer’s disease.Int. J. Biol. Macromol.20179519920310.1016/j.ijbiomac.2016.11.06227871793
    [Google Scholar]
  40. ManjunathanR. PeriyaswamiV. MitraK. RositaA.S. PandyaM. SelvarajJ. RaviL. DevarajanN. DobleM. Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein.BMC Bioinformatics202223118010.1186/s12859‑022‑04724‑935578172
    [Google Scholar]
  41. DeyD. HossainR. BiswasP. PaulP. IslamM.A. EmaT.I. GainB.K. HasanM.M. BibiS. IslamM.T. RahmanM.A. KimB. Amentoflavone derivatives significantly act towards the main protease (3CLPRO/MPRO) of SARS-CoV-2: In silico admet profiling, molecular docking, molecular dynamics simulation, network pharmacology.Mol. Divers.202327285787110.1007/s11030‑022‑10459‑935639226
    [Google Scholar]
  42. JainA.N. NichollsA. Recommendations for evaluation of computational methods.J. Comput. Aided Mol. Des.2008223-413313910.1007/s10822‑008‑9196‑518338228
    [Google Scholar]
  43. HussainM. JabeenN. AmanullahA. Ashraf BaigA. AzizB. ShabbirS. RazaF. UddinN. Molecular docking between human TMPRSS2 and SARS-CoV-2 spike protein: Conformation and intermolecular interactions.AIMS Microbiol.20206335036010.3934/microbiol.202002133029570
    [Google Scholar]
  44. GangadharappaB.S. SharathR. RevanasiddappaP.D. ChandramohanV. BalasubramaniamM. VardhineniT.P. Structural insights of metallo-beta-lactamase revealed an effective way of inhibition of enzyme by natural inhibitors.J. Biomol. Struct. Dyn.202038133757377110.1080/07391102.2019.166726531514687
    [Google Scholar]
  45. PrasanthD.S.N.B.K. MurahariM. ChandramohanV. PandaS.P. AtmakuriL.R. GuntupalliC. In silico identification of potential inhibitors from Cinnamon against main protease and spike glycoprotein of SARS CoV-2.J. Biomol. Struct. Dyn.202139134618463210.1080/07391102.2020.177912932567989
    [Google Scholar]
  46. AiY. SongW. KostyukovA.A. YinY. KuzminV.A. LinW. Fluorescent probe for evaluating the preventive utility of plumbagin in ischemia–reperfusion injury.J. Photochem. Photobiol. Chem.202445411572310.1016/j.jphotochem.2024.115723
    [Google Scholar]
  47. SonT.G. CamandolaS. ArumugamT.V. CutlerR.G. TelljohannR.S. MughalM.R. MooreT.A. LuoW. YuQ.S. JohnsonD.A. JohnsonJ.A. GreigN.H. MattsonM.P. Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia.J. Neurochem.201011251316132610.1111/j.1471‑4159.2009.06552.x20028456
    [Google Scholar]
  48. NakhateK.T. BharneA.P. VermaV.S. AruD.N. KokareD.M. Plumbagin ameliorates memory dysfunction in streptozotocin induced Alzheimer’s disease via activation of Nrf2/ARE pathway and inhibition of β-secretase.Biomed. Pharmacother.201810137939010.1016/j.biopha.2018.02.05229501041
    [Google Scholar]
  49. SuY. LiM. WangQ. XuX. QinP. HuangH. ZhangY. ZhouY. YanJ. 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.2022202211410.1155/2022/183727836589679
    [Google Scholar]
  50. MessehaS.S. ZarmouhN.O. MendoncaP. KoltaM.G. SolimanK.F.A. The attenuating effects of plumbagin on pro-inflammatory cytokine expression in LPS-activated BV-2 microglial cells.J. Neuroimmunol.201731312913710.1016/j.jneuroim.2017.09.00728950995
    [Google Scholar]
  51. JangraA. ChadhaV. KumarD. KumarV. AroraM.K. Neuroprotective and acetylcholinesterase inhibitory activity of plumbagin in ICV-LPS induced behavioral deficits in rats.CRBS20232100060
    [Google Scholar]
  52. KhadrawyY.A. SalemA.M. El-ShamyK.A. AhmedE.K. FadlN.N. HosnyE.N. Neuroprotective and therapeutic effect of caffeine on the rat model of Parkinson’s disease induced by rotenone.J. Diet. Suppl.201714555357210.1080/19390211.2016.127591628301304
    [Google Scholar]
  53. RamkumarM. RajasankarS. JohnsonS.W.M. PrabuK. GobiV.V. Demethoxycurcumin ameliorates rotenone-induced toxicity in rats.Front. Biosci. (Elite Ed.)201911111130468633
    [Google Scholar]
  54. Medeiros-LinardC.F.B. Andrade-da-CostaB.L.S. AugustoR.L. SerenikiA. TrevisanM.T.S. PerreiraR.C.R. de SouzaF.T.C. BrazG.R.F. LagranhaC.J. de SouzaI.A. WanderleyA.G. SmailliS.S. LafayetteS.S.L. Anacardic acids from cashew nuts prevent behavioral changes and oxidative stress induced by rotenone in a rat model of Parkinson’s disease.Neurotox. Res.201834225026210.1007/s12640‑018‑9882‑629520721
    [Google Scholar]
  55. HeJ.Y. LiD.D. WenQ. QinT.Y. LongH. ZhangS.B. ZhangF. Synergistic effects of lipopolysaccharide and rotenone on dopamine neuronal damage in rats.CNS Neurosci. Ther.20232982281229110.1111/cns.1418036942519
    [Google Scholar]
  56. EddinL.B. AzimullahS. JhaN.K. Nagoor MeeranM.F. BeiramR. OjhaS. Limonene, a monoterpene, mitigates rotenone-induced dopaminergic neurodegeneration by modulating neuroinflammation, hippo signaling and apoptosis in rats.Int. J. Mol. Sci.2023246522210.3390/ijms2406522236982297
    [Google Scholar]
  57. NamM.H. SaM. JuY.H. ParkM.G. LeeC.J. Revisiting the role of astrocytic MAOB in Parkinson’s disease.Int. J. Mol. Sci.2022238445310.3390/ijms2308445335457272
    [Google Scholar]
  58. JostW.H. A critical appraisal of MAO-B inhibitors in the treatment of Parkinson’s disease.J. Neural Transm. (Vienna)20221295-672373610.1007/s00702‑022‑02465‑w35107654
    [Google Scholar]
  59. HegdeH.V. NairV. KumarD. PatilP.A. RoyS. KholkuteS.D. Comparative toxicity profiles of Plumbago zeylanica L. root petroleum ether, acetone and hydroalcoholic extracts in Wistar rats.Ayu201536332933410.4103/0974‑8520.18275027313422
    [Google Scholar]
  60. TeixeiraC.J.R. dos SantosB.P. SaraivaC.J.C. PedrozaH.P. OlorisS.C.S. Soto-BlancoB. TLC and HPLC methods for the determination of plumbagin for the diagnosis of poisoning by Plumbago scandens L.Toxicon202423910763410.1016/j.toxicon.2024.10763438307130
    [Google Scholar]
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  • Article Type:
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Keyword(s): dopamine; MAO-B; neuroprotective; Parkinson's disease; plumbagin; rotenone-toxified rodents
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