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image of Enhanced Neuroprotection in Experiment Multiple Sclerosis through Combined Rosiglitazone and Probiotic-Loaded Solid Lipid Nanoparticles: Modulation of Cellular Signaling Pathways

Abstract

Background

Multiple sclerosis (MS) is a persistent autoimmune condition characterized by inflammation and neurodegeneration. The current efficacy of treatments is limited, which has generated interest in developing neuroprotective strategies. Solid lipid nanoparticles (SLNs) and probiotics are potential drug delivery vehicles for targeting the CNS (Central nervous system), regulating immune responses, and supporting neuroprotection in neurological conditions.

Methods

The study investigates how SLNs containing RSG (rosiglitazone) and probiotics can protect the nervous system in cases of MS. We administered toxin EtBr (Ethidium bromide) from day 1 to day 7, later followed by the treatment from day 8 to day 35. During this time interval, various behavioural parameters have been performed. Further, after 35th day, blood plasma of animals was collected to study complete CBC profiling and animals were sacrificed. Then, biochemical and molecular studies, gross morphology of brain sectioning, histopathological evaluation and estimation of fatty acid content in fecal matter were performed.

Results

RSG shows neuroprotective effects by blocking the STAT-3 and mTOR signaling pathways and increasing the production of PPAR-gamma. GW9662, a PPAR-gamma antagonist given at a dose of 2 mg/kg (, was utilized to evaluate the role of PPAR-gamma and to compare the efficacy of RSG and probiotic-loaded SLNs in potentially providing neuroprotection. The relationship between RSG and the STAT-3, mTOR, and PPAR-gamma pathways in MS was confirmed and validated using analysis. RSG and probiotic-loaded SLNs modulate the complete blood profiling of rats and improve the symptoms of MS. We assessed the diagnostic capabilities of different biological samples such as cerebrospinal fluid, blood plasma, and brain homogenates (specifically from the hippocampus, striatum, cortex, and midbrain) to analyze neurochemical changes linked to neurobehavioral changes in the progression of MS.

Conclusion

The study showed that combining RSG and probiotics in an experimental medication form improved symptoms of MS more effectively than using RSG alone. This improvement is likely due to changes in STAT-3, mTOR, and PPAR-gamma signaling pathways.

© 2024 Bentham Science Publishers
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2024-11-01
2024-11-29

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References

  1. Vidal-Jordana A. Montalban X. Multiple Sclerosis. Neuroimaging Clin. N. Am. 2017 27 2 195 204 10.1016/j.nic.2016.12.001 28391781
    [Google Scholar]
  2. Wang K. Song F. Fernandez-Escobar A. Luo G. Wang J.H. Sun Y. The properties of cytokines in multiple sclerosis: Pros and cons. Am. J. Med. Sci. 2018 356 6 552 560 10.1016/j.amjms.2018.08.018 30447707
    [Google Scholar]
  3. Fernández Ó. Costa-Frossard L. Martínez-Ginés M. Montero P. Prieto J.M. Ramió L. The broad concept of “spasticity-plus syndrome” in multiple sclerosis: A possible new concept in the management of multiple sclerosis symptoms. Front. Neurol. 2020 11 152 10.3389/fneur.2020.00152 32256440
    [Google Scholar]
  4. Pithadia A. Jain S. Navale A. Pathogenesis and treatment of multiple sclerosis (MS). Int. J. Neurol. 2009 10 2 1 20
    [Google Scholar]
  5. Goodin D.S. Khankhanian P. Gourraud P.A. Vince N. The nature of genetic and environmental susceptibility to multiple sclerosis. PLoS One 2021 16 3 e0246157 10.1371/journal.pone.0246157 33750973
    [Google Scholar]
  6. Naegele M. Martin R. The good and the bad of neuroinflammation in multiple sclerosis. Handb. Clin. Neurol. 2014 122 59 87 10.1016/B978‑0‑444‑52001‑2.00003‑0 24507513
    [Google Scholar]
  7. Xin P. Xu X. Deng C. Liu S. Wang Y. Zhou X. Ma H. Wei D. Sun S. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int. Immunopharmacol. 2020 80 106210 10.1016/j.intimp.2020.106210 31972425
    [Google Scholar]
  8. Philips R.L. Wang Y. Cheon H. Kanno Y. Gadina M. Sartorelli V. Horvath C.M. Darnell J.E. Jr Stark G.R. O’Shea J.J. The JAK-STAT pathway at 30: Much learned, much more to do. Cell 2022 185 21 3857 3876 10.1016/j.cell.2022.09.023 36240739
    [Google Scholar]
  9. Yang X. Yv Q. Ye F. Chen S. He Z. Li W. Dong F. Echinacoside protects dopaminergic neurons through regulating IL-6/JAK2/STAT3 pathway in Parkinson’s disease model. Front. Pharmacol. 2022 13 848813 10.3389/fphar.2022.848813 35281889
    [Google Scholar]
  10. Lashgari N.A. Roudsari N.M. Momtaz S. Sathyapalan T. Abdolghaffari A.H. Sahebkar A. The involvement of JAK/STAT signaling pathway in the treatment of Parkinson’s disease. J. Neuroimmunol. 2021 361 577758 10.1016/j.jneuroim.2021.577758 34739911
    [Google Scholar]
  11. Chiba T. Yamada M. Aiso S. Targeting the JAK2/STAT3 axis in Alzheimer’s disease. Expert Opin. Ther. Targets 2009 13 10 1155 1167 10.1517/14728220903213426 19663649
    [Google Scholar]
  12. Rusek M. Smith J. El-Khatib K. Aikins K. Czuczwar S.J. Pluta R. The role of the JAK/STAT signaling pathway in the pathogenesis of Alzheimer’s Disease: New potential treatment target. Int. J. Mol. Sci. 2023 24 1 864 10.3390/ijms24010864 36614305
    [Google Scholar]
  13. Träger U. Magnusson A. Lahiri Swales N. Wild E. North J. Lowdell M. Björkqvist M. JAK/STAT signalling in Huntington’s disease immune cells. PLoS Curr. 2013 5 ecurrents.hd.5791c897b5c3bebeed93b1d1da0c0648 10.1371/currents.hd.5791c897b5c3bebeed93b1d1da0c0648 24459609
    [Google Scholar]
  14. Kooshki L. Zarneshan S.N. Fakhri S. Moradi S.Z. Echeverria J. The pivotal role of JAK/STAT and IRS/PI3K signaling pathways in neurodegenerative diseases: Mechanistic approaches to polyphenols and alkaloids. Phytomedicine 2023 112 154686 10.1016/j.phymed.2023.154686 36804755
    [Google Scholar]
  15. Kumar N. Sharma N. Mehan S. Connection between JAK/STAT and PPARγ signaling during the progression of multiple sclerosis: Insights into the modulation of T-cells and immune responses in the brain. Curr. Mol. Pharmacol. 2021 14 5 823 837 10.2174/1874467214666210301121432 33645493
    [Google Scholar]
  16. Benveniste E.N. Liu Y. McFarland B.C. Qin H. Involvement of the janus kinase/signal transducer and activator of transcription signaling pathway in multiple sclerosis and the animal model of experimental autoimmune encephalomyelitis. J. Interferon Cytokine Res. 2014 34 8 577 588 10.1089/jir.2014.0012 25084174
    [Google Scholar]
  17. Schmitz T. Chew L.J. Cytokines and myelination in the central nervous system. ScientificWorldJournal 2008 8 1119 1147 10.1100/tsw.2008.140 18979053
    [Google Scholar]
  18. Liu Y. Holdbrooks A.T. De Sarno P. Rowse A.L. Yanagisawa L.L. McFarland B.C. Harrington L.E. Raman C. Sabbaj S. Benveniste E.N. Qin H. Therapeutic efficacy of suppressing the Jak/STAT pathway in multiple models of experimental autoimmune encephalomyelitis. J. Immunol. 2014 192 1 59 72 10.4049/jimmunol.1301513 24323580
    [Google Scholar]
  19. Van Rompaey L. Galien R. van der Aar E.M. Clement-Lacroix P. Nelles L. Smets B. Lepescheux L. Christophe T. Conrath K. Vandeghinste N. Vayssiere B. De Vos S. Fletcher S. Brys R. van ’t Klooster G. Feyen J.H.M. Menet C. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J. Immunol. 2013 191 7 3568 3577 10.4049/jimmunol.1201348 24006460
    [Google Scholar]
  20. Alhazzani K. Ahmad S.F. Al-Harbi N.O. Attia S.M. Bakheet S.A. Sarawi W. Alqarni S.A. Algahtani M. Nadeem A. Pharmacological inhibition of STAT3 by Stattic Ameliorates clinical symptoms and reduces autoinflammation in myeloid, lymphoid, and neuronal tissue compartments in relapsing–remitting model of experimental autoimmune encephalomyelitis in SJL/J Mice. Pharmaceutics 2021 13 7 925 10.3390/pharmaceutics13070925 34206429
    [Google Scholar]
  21. Panwar V. Singh A. Bhatt M. Tonk R.K. Azizov S. Raza A.S. Sengupta S. Kumar D. Garg M. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease. Signal Transduct. Target. Ther. 2023 8 1 375 10.1038/s41392‑023‑01608‑z 37779156
    [Google Scholar]
  22. Dello Russo C. Lisi L. Feinstein D.L. Navarra P. mTOR kinase, a key player in the regulation of glial functions: Relevance for the therapy of multiple sclerosis. Glia 2013 61 3 301 311 10.1002/glia.22433 23044764
    [Google Scholar]
  23. Vakrakou A.G. Alexaki A. Brinia M.E. Anagnostouli M. Stefanis L. Stathopoulos P. The mTOR signaling pathway in multiple sclerosis; from animal models to human data. Int. J. Mol. Sci. 2022 23 15 8077 10.3390/ijms23158077 35897651
    [Google Scholar]
  24. Figlia G Gerber D Suter U. Myelination and mTOR. Glia 2018 66 4 693 707 10.1002/glia.23273
    [Google Scholar]
  25. Giacoppo S. Pollastro F. Grassi G. Bramanti P. Mazzon E. Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis. Fitoterapia 2017 116 77 84 10.1016/j.fitote.2016.11.010 27890794
    [Google Scholar]
  26. Buonvicino D. Pratesi S. Ranieri G. Pistolesi A. Guasti D. Chiarugi A. The mitochondriogenic but not the immunosuppressant effects of mTOR inhibitors prompt neuroprotection and delay disease evolution in a mouse model of progressive multiple sclerosis. Neurobiol. Dis. 2024 191 106387 10.1016/j.nbd.2023.106387 38142841
    [Google Scholar]
  27. Hou H. Cao R. Quan M. Sun Y. Sun H. Zhang J. Li B. Guo L. Song X. Rapamycin and fingolimod modulate Treg/Th17 cells in experimental autoimmune encephalomyelitis by regulating the Akt-mTOR and MAPK/ERK pathways. J. Neuroimmunol. 2018 324 26 34 10.1016/j.jneuroim.2018.08.012 30205205
    [Google Scholar]
  28. Luo W. Xu H. Xu L. Jiang W. Chen C. Chang Y. Liu C. Tian Z. Qiu X. Xie C. Li X. Chen H. Lai S. Wu L. Cui Y. Tang C. Qiu W. Remyelination in neuromyelitis optica spectrum disorder is promoted by edaravone through mTORC1 signaling activation. Glia 2023 71 2 284 304 10.1002/glia.24271 36089914
    [Google Scholar]
  29. Hou H. Miao J. Cao R. Han M. Sun Y. Liu X. Guo L. Rapamycin ameliorates experimental autoimmune encephalomyelitis by suppressing the mTOR-STAT3 pathway. Neurochem. Res. 2017 42 10 2831 2840 10.1007/s11064‑017‑2296‑7 28600752
    [Google Scholar]
  30. Chinetti G. Fruchart J.C. Staels B. Peroxisome proliferator-activated receptors (PPARs): Nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm. Res. 2000 49 10 497 505 10.1007/s000110050622 11089900
    [Google Scholar]
  31. Luconi M. Cantini G. Serio M. Peroxisome proliferator-activated receptor gamma (PPARγ): Is the genomic activity the only answer? Steroids 2010 75 8-9 585 594 10.1016/j.steroids.2009.10.012 19900469
    [Google Scholar]
  32. Mal S. Dwivedi A.R. Kumar V. Kumar N. Kumar B. Kumar V. Role of peroxisome proliferator-activated receptor gamma (PPARγ) in different disease states: Recent updates. Curr. Med. Chem. 2021 28 16 3193 3215 10.2174/1875533XMTA4rMjACx 32674727
    [Google Scholar]
  33. Storer P.D. Xu J. Chavis J. Drew P.D. Peroxisome proliferator-activated receptor-gamma agonists inhibit the activation of microglia and astrocytes: Implications for multiple sclerosis. J. Neuroimmunol. 2005 161 1-2 113 122 10.1016/j.jneuroim.2004.12.015 15748950
    [Google Scholar]
  34. Vallée A. Vallée J.N. Guillevin R. Lecarpentier Y. Interactions between the canonical WNT/beta-catenin pathway and PPAR gamma on neuroinflammation, demyelination, and remyelination in multiple sclerosis. Cell. Mol. Neurobiol. 2018 38 4 783 795 10.1007/s10571‑017‑0550‑9 28905149
    [Google Scholar]
  35. Vallée A. Lecarpentier Y. Guillevin R. Vallée J.N. Demyelination in multiple sclerosis: Reprogramming energy metabolism and potential PPARγ agonist treatment approaches. Int. J. Mol. Sci. 2018 19 4 1212 10.3390/ijms19041212 29659554
    [Google Scholar]
  36. Dunn S.E. Bhat R. Straus D.S. Sobel R.A. Axtell R. Johnson A. Nguyen K. Mukundan L. Moshkova M. Dugas J.C. Chawla A. Steinman L. Peroxisome proliferator–activated receptor δ limits the expansion of pathogenic Th cells during central nervous system autoimmunity. J. Exp. Med. 2010 207 8 1599 1608 10.1084/jem.20091663 20624891
    [Google Scholar]
  37. Fakan B. Szalardy L. Vecsei L. Exploiting the therapeutic potential of endogenous immunomodulatory systems in multiple sclerosis—special focus on the peroxisome proliferator-activated receptors (PPARs) and the kynurenines. Int. J. Mol. Sci. 2019 20 2 426 10.3390/ijms20020426 30669473
    [Google Scholar]
  38. Hucke S. Floßdorf J. Grützke B. Dunay I.R. Frenzel K. Jungverdorben J. Linnartz B. Mack M. Peitz M. Brüstle O. Kurts C. Klockgether T. Neumann H. Prinz M. Wiendl H. Knolle P. Klotz L. Licensing of myeloid cells promotes central nervous system autoimmunity and is controlled by peroxisome proliferator-activated receptor γ. Brain 2012 135 5 1586 1605 10.1093/brain/aws058 22447120
    [Google Scholar]
  39. Choi J.M. Bothwell A.L.M. The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases. Mol. Cells 2012 33 3 217 222 10.1007/s10059‑012‑2297‑y 22382683
    [Google Scholar]
  40. Racke M.K. Gocke A.R. Muir M. Diab A. Drew P.D. Lovett-Racke A.E. Nuclear receptors and autoimmune disease: The potential of PPAR agonists to treat multiple sclerosis. J. Nutr. 2006 136 3 700 703 10.1093/jn/136.3.700 16484546
    [Google Scholar]
  41. Smith E.S. Porterfield J.E. Kannan R.M. Leveraging the interplay of nanotechnology and neuroscience: Designing new avenues for treating central nervous system disorders. Adv. Drug Deliv. Rev. 2019 148 181 203 10.1016/j.addr.2019.02.009 30844410
    [Google Scholar]
  42. Siddiqui L Mishra H Talegaonkar S Rai M. Nanoformulations: Opportunities and challenges Nanoformulations in Human Health: Challenges and Approaches Springer 2020 3 12 10.1007/978‑3‑030‑41858‑8_1
    [Google Scholar]
  43. Pottoo F.H. Sharma S. Javed M.N. Barkat M.A. Harshita Alam M.S. Naim M.J. Alam O. Ansari M.A. Barreto G.E. Ashraf G.M. Lipid-based nanoformulations in the treatment of neurological disorders. Drug Metab. Rev. 2020 52 1 185 204 10.1080/03602532.2020.1726942 32116044
    [Google Scholar]
  44. Chenthamara D. Subramaniam S. Ramakrishnan S.G. Krishnaswamy S. Essa M.M. Lin F.H. Qoronfleh M.W. Therapeutic efficacy of nanoparticles and routes of administration. Biomater. Res. 2019 23 1 20 10.1186/s40824‑019‑0166‑x 31832232
    [Google Scholar]
  45. Ojha S. Kumar B. Chadha H. Neuroprotective potential of Dimethyl Fumarate-loaded polymeric nanoparticles against multiple sclerosis. Indian J. Pharm. Sci. 2019 81 3 10.36468/pharmaceutical‑sciences.535
    [Google Scholar]
  46. Ghalamfarsa G. Hojjat-Farsangi M. Mohammadnia-Afrouzi M. Anvari E. Farhadi S. Yousefi M. Jadidi-Niaragh F. Application of nanomedicine for crossing the blood–brain barrier: Theranostic opportunities in multiple sclerosis. J. Immunotoxicol. 2016 13 5 603 619 10.3109/1547691X.2016.1159264 27416019
    [Google Scholar]
  47. Damavandi A.R. Mirmosayyeb O. Ebrahimi N. Zalpoor H. khalilian P. Yahiazadeh S. Eskandari N. Rahdar A. Kumar P.S. Pandey S. Advances in nanotechnology versus stem cell therapy for the theranostics of multiple sclerosis disease. Appl. Nanosci. 2023 13 6 4043 4073 10.1007/s13204‑022‑02698‑x
    [Google Scholar]
  48. Pathak R. Afaq A. Blonde L. Thiazolidinediones in the treatment of managed care patients with type 2 diabetes. Am. J. Manag. Care 2002 8 16 Suppl. S483 S494 12408411
    [Google Scholar]
  49. Li Y. Zhu Z.Y. Lu B.W. Huang T.T. Zhang Y.M. Zhou N.Y. Xuan W. Chen Z.A. Wen D.X. Yu W.F. Li P.Y. Rosiglitazone ameliorates tissue plasminogen activator‐induced brain hemorrhage after stroke. CNS Neurosci. Ther. 2019 25 12 1343 1352 10.1111/cns.13260 31756041
    [Google Scholar]
  50. Shao Z.Q. Liu Z.J. Neuroinflammation and neuronal autophagic death were suppressed via Rosiglitazone treatment: New evidence on neuroprotection in a rat model of global cerebral ischemia. J. Neurol. Sci. 2015 349 1-2 65 71 10.1016/j.jns.2014.12.027 25623802
    [Google Scholar]
  51. Nelson M.L. Pfeifer J.A. Hickey J.P. Collins A.E. Kalisch B.E. Exploring Rosiglitazone’s potential to treat Alzheimer’s disease through the modulation of brain-derived neurotrophic factor. Biology 2023 12 7 1042 10.3390/biology12071042 37508471
    [Google Scholar]
  52. San Y.Z. Liu Y.U. Zhang Y.U. Shi P.P. Zhu Y.U.L.A.N. Peroxisome proliferator-activated receptor-γ agonist inhibits the mammalian target of rapamycin signaling pathway and has a protective effect in a rat model of status epilepticus. Mol. Med. Rep. 2015 12 2 1877 1883 10.3892/mmr.2015.3641 25891824
    [Google Scholar]
  53. Park E.J. Park S.Y. Joe E. Jou I. 15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia. J. Biol. Chem. 2003 278 17 14747 14752 10.1074/jbc.M210819200 12584205
    [Google Scholar]
  54. Chen Y.C. Wu J.S. Tsai H.D. Huang C.Y. Chen J.J. Sun G.Y. Lin T.N. Peroxisome proliferator-activated receptor gamma (PPAR-γ) and neurodegenerative disorders. Mol. Neurobiol. 2012 46 1 114 124 10.1007/s12035‑012‑8259‑8 22434581
    [Google Scholar]
  55. Mörkl S. Butler M.I. Holl A. Cryan J.F. Dinan T.G. Probiotics and the microbiota-gut-brain axis: Focus on psychiatry. Curr. Nutr. Rep. 2020 9 3 171 182 10.1007/s13668‑020‑00313‑5 32406013
    [Google Scholar]
  56. Morshedi M. Hashemi R. Moazzen S. Sahebkar A. Hosseinifard E.S. Immunomodulatory and anti-inflammatory effects of probiotics in multiple sclerosis: A systematic review. J. Neuroinflammation 2019 16 1 231 10.1186/s12974‑019‑1611‑4 31752913
    [Google Scholar]
  57. Kumar N. Sahoo N.K. Mehan S. verma B. The importance of gut-brain axis and use of probiotics as a treatment strategy for multiple sclerosis. Mult. Scler. Relat. Disord. 2023 71 104547 10.1016/j.msard.2023.104547 36805171
    [Google Scholar]
  58. Jiang J. Chu C. Wu C. Wang C. Zhang C. Li T. Zhai Q. Yu L. Tian F. Chen W. Efficacy of probiotics in multiple sclerosis: A systematic review of preclinical trials and meta-analysis of randomized controlled trials. Food Funct. 2021 12 6 2354 2377 10.1039/D0FO03203D 33629669
    [Google Scholar]
  59. Salami M. Kouchaki E. Asemi Z. Tamtaji O.R. How probiotic bacteria influence the motor and mental behaviors as well as immunological and oxidative biomarkers in multiple sclerosis? A double blind clinical trial. J. Funct. Foods 2019 52 8 13 10.1016/j.jff.2018.10.023
    [Google Scholar]
  60. Asghari K.M. Dolatkhah N. Ayromlou H. Mirnasiri F. Dadfar T. Hashemian M. The effect of probiotic supplementation on the clinical and para-clinical findings of multiple sclerosis: a randomized clinical trial. Sci. Rep. 2023 13 1 18577 10.1038/s41598‑023‑46047‑6 37903945
    [Google Scholar]
  61. Sadeghirashed S. Kazemi F. Taheri S. Ebrahimi M.T. Arasteh J. A novel probiotic strain exerts therapeutic effects on mouse model of multiple sclerosis by altering the expression of inflammasome and IDO genes and modulation of T helper cytokine profile. Metab. Brain Dis. 2022 37 1 197 207 10.1007/s11011‑021‑00857‑7 34757579
    [Google Scholar]
  62. Samani S.A. Moloudi M.R. Ramezanzadeh R. Abdi M. Nikkhoo B. Izadpanah E. Roshani D. Abdolahi A. Esmaili P. Hassanzadeh K. Oral Administration of Probiotic Enterococcus durans to Ameliorate Experimental Autoimmune Encephalomyelitis in Mice. Basic Clin. Neurosci. 2022 13 1 35 46 10.32598/bcn.2021.1955.1 36589015
    [Google Scholar]
  63. Kumar N. Tyagi N. Mehan S. Singh A.P. Formulation of solid lipid nanoparticles loaded with Rosiglitazone and Probiotic: Optimization and In-vitro characterization. Recent Pat. Nanotechnol. 2024 18 4 527 542 10.2174/0118722105268801231203144554 38305310
    [Google Scholar]
  64. Pathan A.R. Gaikwad A.B. Viswanad B. Ramarao P. Rosiglitazone attenuates the cognitive deficits induced by high fat diet feeding in rats. Eur. J. Pharmacol. 2008 589 1-3 176 179 10.1016/j.ejphar.2008.06.016 18602098
    [Google Scholar]
  65. Shahsavarian A. Javadi S. Jahanabadi S. Khoshnoodi M. Shamsaee J. Shafaroodi H. Mehr S.E. Dehpour A. Antidepressant-like effect of atorvastatin in the forced swimming test in mice: The role of PPAR-gamma receptor and nitric oxide pathway. Eur. J. Pharmacol. 2014 745 52 58 10.1016/j.ejphar.2014.10.004 25446923
    [Google Scholar]
  66. Sadaghiani M.S. Javadi-Paydar M. Gharedaghi M.H. Fard Y.Y. Dehpour A.R. Antidepressant-like effect of pioglitazone in the forced swimming test in mice: The role of PPAR-gamma receptor and nitric oxide pathway. Behav. Brain Res. 2011 224 2 336 343 10.1016/j.bbr.2011.06.011 21704657
    [Google Scholar]
  67. Kapoor T. Mehan S. Suri M. Sharma N. Kumar N. Narula A.S. Alshammari A. Alasmari A.F. Alharbi M. Assiri M.A. Kalfin R. Forskolin, an Adenylcyclase/cAMP/CREB signaling activator restoring Myelin-associated oligodendrocyte destruction in experimental ethidium bromide model of multiple sclerosis. Cells 2022 11 18 2771 10.3390/cells11182771 36139346
    [Google Scholar]
  68. Upadhayay S. Mehan S. Prajapati A. Sethi P. Suri M. Zawawi A. Almashjary M.N. Tabrez S. Nrf2/HO-1 signaling stimulation through Acetyl-11-Keto-Beta-Boswellic acid (AKBA) provides neuroprotection in ethidium bromide-induced experimental model of multiple sclerosis. Genes (Basel) 2022 13 8 1324 10.3390/genes13081324 35893061
    [Google Scholar]
  69. Khera R. Mehan S. Bhalla S. Kumar S. Alshammari A. Alharbi M. Sadhu S.S. Guggulsterone mediated JAK/STAT and PPAR-Gamma modulation prevents neurobehavioral and neurochemical abnormalities in propionic acid-induced experimental model of autism. Molecules 2022 27 3 889 10.3390/molecules27030889 35164154
    [Google Scholar]
  70. Kumar N. Sharma N. Khera R. Gupta R. Mehan S. Guggulsterone ameliorates ethidium bromide-induced experimental model of multiple sclerosis via restoration of behavioral, molecular, neurochemical and morphological alterations in rat brain. Metab. Brain Dis. 2021 36 5 911 925 10.1007/s11011‑021‑00691‑x 33635478
    [Google Scholar]
  71. Sharma N. Upadhayay S. Shandilya A. Sahu R. Singh A. Rajkhowa B. Mehan S. Neuroprotection by solanesol against ethidium bromide-induced multiple sclerosis-like neurobehavioral, molecular, and neurochemical alterations in experimental rats. Phytomedicine Plus 2021 1 4 100051 10.1016/j.phyplu.2021.100051
    [Google Scholar]
  72. Singh A. Upadhayay S. Mehan S. Inhibition of c-JNK/p38MAPK signaling pathway by Apigenin prevents neurobehavioral and neurochemical defects in ethidium bromide-induced experimental model of multiple sclerosis in rats: Evidence from CSF, blood plasma and brain samples. Phytomedicine Plus 2021 1 4 100139 10.1016/j.phyplu.2021.100139
    [Google Scholar]
  73. Goudarzvand M. Javan M. Mirnajafi-Zadeh J. Mozafari S. Tiraihi T. Vitamins E and D3 attenuate demyelination and potentiate remyelination processes of hippocampal formation of rats following local injection of ethidium bromide. Cell. Mol. Neurobiol. 2010 30 2 289 299 10.1007/s10571‑009‑9451‑x 19768531
    [Google Scholar]
  74. Shandilya A. Mehan S. Kumar S. Sethi P. Narula A.S. Alshammari A. Alharbi M. Alasmari A.F. Activation of IGF-1/GLP-1 Signalling via 4-Hydroxyisoleucine Prevents Motor Neuron Impairments in Experimental ALS-Rats Exposed to Methylmercury-Induced Neurotoxicity. Molecules 2022 27 12 3878 10.3390/molecules27123878 35745001
    [Google Scholar]
  75. Yadav R.K. Mehan S. Sahu R. Kumar S. Khan A. Makeen H.A. Al Bratty M. Protective effects of apigenin on methylmercury-induced behavioral/neurochemical abnormalities and neurotoxicity in rats. Hum. Exp. Toxicol. 2022 41 10.1177/09603271221084276 35373622
    [Google Scholar]
  76. Rahi S. Gupta R. Sharma A. Mehan S. Smo-Shh signaling activator purmorphamine ameliorates neurobehavioral, molecular, and morphological alterations in an intracerebroventricular propionic acid-induced experimental model of autism. Hum. Exp. Toxicol. 2021 40 11 1880 1898 10.1177/09603271211013456 33906504
    [Google Scholar]
  77. Minj E. Upadhayay S. Mehan S. Nrf2/HO-1 Signaling Activator Acetyl-11-keto-beta Boswellic Acid (AKBA)-Mediated neuroprotection in methyl mercury-induced experimental model of aLS. Neurochem. Res. 2021 46 11 2867 2884 10.1007/s11064‑021‑03366‑2 34075522
    [Google Scholar]
  78. Rajkhowa B. Mehan S. Sethi P. Prajapati A. Suri M. Kumar S. Bhalla S. Narula A.S. Alshammari A. Alharbi M. Alkahtani N. Alghamdi S. Kalfin R. Activating SIRT-1 signalling with the mitochondrial-CoQ10 activator Solanesol improves neurobehavioral and neurochemical defects in Ouabain-induced experimental model of bipolar disorder. Pharmaceuticals (Basel) 2022 15 8 959 10.3390/ph15080959 36015107
    [Google Scholar]
  79. Bergadano A. Amen E.M. Jacobsen B. Belli S. Vandjour A. Rapp C. Senn C. A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs. J. Biol. Methods 2019 6 1 1 10.14440/jbm.2019.265 31453257
    [Google Scholar]
  80. Bhalla S. Mehan S. 4-hydroxyisoleucine mediated IGF-1/GLP-1 signalling activation prevents propionic acid-induced autism-like behavioural phenotypes and neurochemical defects in experimental rats. Neuropeptides 2022 96 102296 10.1016/j.npep.2022.102296 36307249
    [Google Scholar]
  81. Tsao S.P. Nurrahma B.A. Kumar R. Wu C.H. Yeh T.H. Chiu C.C. Lee Y.P. Liao Y.C. Huang C.H. Yeh Y.T. Huang H.Y. Probiotic enhancement of antioxidant capacity and alterations of gut microbiota composition in 6-hydroxydopamin-induced parkinson’s disease rats. Antioxidants 2021 10 11 1823 10.3390/antiox10111823 34829694
    [Google Scholar]
  82. Hao Z. Wang W. Guo R. Liu H. Faecalibacterium prausnitzii (ATCC 27766) has preventive and therapeutic effects on chronic unpredictable mild stress-induced depression-like and anxiety-like behavior in rats. Psychoneuroendocrinology 2019 104 132 142 10.1016/j.psyneuen.2019.02.025 30844607
    [Google Scholar]
  83. Chhabra S. Mehan S. Khan Z. Gupta G.D. Narula A.S. Matrine mediated neuroprotective potential in experimental multiple sclerosis: Evidence from CSF, blood markers, brain samples and in-silico investigations. J. Neuroimmunol. 2023 384 578200 10.1016/j.jneuroim.2023.578200 37774554
    [Google Scholar]
  84. Sahu R. Mehan S. Kumar S. Prajapati A. Alshammari A. Alharbi M. Assiri M.A. Narula A.S. Effect of alpha-mangostin in the prevention of behavioural and neurochemical defects in methylmercury-induced neurotoxicity in experimental rats. Toxicol. Rep. 2022 9 977 998 10.1016/j.toxrep.2022.04.023 35783250
    [Google Scholar]
  85. Tiwari A. Khera R. Rahi S. Mehan S. Makeen H.A. Khormi Y.H. Rehman M.U. Khan A. Neuroprotective effect of α-Mangostin in Ameliorating Propionic Acid-Induced experimental model of autism in wistar rats. Brain Sci. 2021 11 3 288 10.3390/brainsci11030288 33669120
    [Google Scholar]
  86. Jadaun K.S. Mehan S. Sharma A. Siddiqui E.M. Kumar S. Alsuhaymi N. Neuroprotective effect of Chrysophanol as a PI3K/AKT/mTOR signaling inhibitor in an experimental model of autologous blood-induced intracerebral hemorrhage. Curr. Med. Sci. 2022 42 2 249 266 10.1007/s11596‑022‑2496‑x 35079960
    [Google Scholar]
  87. Albekairi T.H. Kamra A. Bhardwaj S. Mehan S. Giri A. Suri M. Alshammari A. Alharbi M. Alasmari A.F. Narula A.S. Kalfin R. Beta-boswellic acid reverses 3-Nitropropionic Acid-induced molecular, mitochondrial, and histopathological defects in experimental rat model of Huntington’s disease. Biomedicines 2022 10 11 2866 10.3390/biomedicines10112866 36359390
    [Google Scholar]
  88. Lotfi A. Soleimani M. Ghasemi N. Astaxanthin reduces demyelination and oligodendrocytes death in a rat model of multiple sclerosis. Cell J. 2021 22 4 565 571 10.220742/Fcellj.2021.6999 32347051
    [Google Scholar]
  89. Adelusi T.I. Oyedele A.Q.K. Boyenle I.D. Ogunlana A.T. Adeyemi R.O. Ukachi C.D. Idris M.O. Olaoba O.T. Adedotun I.O. Kolawole O.E. Xiaoxing Y. Abdul-Hammed M. Molecular modeling in drug discovery. Informatics in Medicine Unlocked 2022 29 100880 10.1016/j.imu.2022.100880
    [Google Scholar]
  90. Kumar S. Abbas F. Ali I. Gupta M.K. Kumar S. Garg M. Kumar D. Integrated network pharmacology and in-silico approaches to decipher the pharmacological mechanism of Selaginella tamariscina in the treatment of non-small cell lung cancer. Phytomedicine Plus 2023 3 2 100419 10.1016/j.phyplu.2023.100419
    [Google Scholar]
  91. Zak M. Hanan E.J. Lupardus P. Brown D.G. Robinson C. Siu M. Lyssikatos J.P. Romero F.A. Zhao G. Kellar T. Mendonca R. Ray N.C. Goodacre S.C. Crackett P.H. McLean N. Hurley C.A. Yuen P. Cheng Y.X. Liu X. Liimatta M. Kohli P.B. Nonomiya J. Salmon G. Buckley G. Lloyd J. Gibbons P. Ghilardi N. Kenny J.R. Johnson A. Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling. Bioorg. Med. Chem. Lett. 2019 29 12 1522 1531 10.1016/j.bmcl.2019.04.008 30981576
    [Google Scholar]
  92. Hu T Yeh JE Pinello L Jacob J Chakravarthy S Yuan GC Chopra R Frank DA Impact of the N-terminal domain of STAT3 in STAT3-Dependent transcriptional activity. Mol Cell Biol 2023 35 19 3284 3300 10.1128/MCB.00060‑15
    [Google Scholar]
  93. Yang H. Rudge D.G. Koos J.D. Vaidialingam B. Yang H.J. Pavletich N.P. mTOR kinase structure, mechanism and regulation. Nature 2013 497 7448 217 223 10.1038/nature12122 23636326
    [Google Scholar]
  94. Nolte RT Wisely GB Westin S Cobb JE Lambert MH Kurokawa R Rosenfeld MG Willson TM Glass CK Milburn MV Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-γ. Nature 1998 395 6698 137 143 10.1038/25931
    [Google Scholar]
  95. Cosconati S Forli S Perryman AL Harris R Goodsell DS Olson AJ Virtual screening with AutoDock: Theory and practice. Expert Opin Drug Discov 2010 5 6 597 607 10.1517/17460441.2010.484460
    [Google Scholar]
  96. Morris G.M. Huey R. Lindstrom W. Sanner M.F. Belew R.K. Goodsell D.S. Olson A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 2009 30 16 2785 2791 10.1002/jcc.21256 19399780
    [Google Scholar]
  97. O’Boyle N.M. Banck M. James C.A. Morley C. Vandermeersch T. Hutchison G.R. Open Babel: An open chemical toolbox. J. Cheminform. 2011 3 1 33 10.1186/1758‑2946‑3‑33 21982300
    [Google Scholar]
  98. Dallakyan S. Olson A.J. Small-molecule library screening by docking with PyRx. Methods Mol. Biol. 2015 1263 243 250 10.1007/978‑1‑4939‑2269‑7_19 25618350
    [Google Scholar]
  99. Kumar S Sengupta S Ali I Gupta MK Lalhlenmawia H Azizov S Kumar D Identification and exploration of quinazoline-1,2,3-triazole inhibitors targeting EGFR in lung cancer J Biomol Struct Dyn 2023 41 21 11353 11372 10.1080/07391102.2023.2204360
    [Google Scholar]
  100. Reynolds R. Roncaroli F. Nicholas R. Radotra B. Gveric D. Howell O. The neuropathological basis of clinical progression in multiple sclerosis. Acta Neuropathol. 2011 122 2 155 170 10.1007/s00401‑011‑0840‑0 21626034
    [Google Scholar]
  101. Geurts J.J.G. Calabrese M. Fisher E. Rudick R.A. Measurement and clinical effect of grey matter pathology in multiple sclerosis. Lancet Neurol. 2012 11 12 1082 1092 10.1016/S1474‑4422(12)70230‑2 23153407
    [Google Scholar]
  102. Jackson S.J. Lee J. Nikodemova M. Fabry Z. Duncan I.D. Quantification of myelin and axon pathology during relapsing progressive experimental autoimmune encephalomyelitis in the Biozzi ABH mouse. J. Neuropathol. Exp. Neurol. 2009 68 6 616 625 10.1097/NEN.0b013e3181a41d23 19458548
    [Google Scholar]
  103. ’t Hart B.A. Experimental autoimmune encephalomyelitis in the common marmoset: a translationally relevant model for the cause and course of multiple sclerosis. Primate Biol. 2019 6 1 17 58 10.5194/pb‑6‑17‑2019 32110715
    [Google Scholar]
  104. Serra-de-Oliveira N. Boilesen S.N. Prado de França Carvalho C. LeSueur-Maluf L. Zollner R.L. Spadari R.C. Medalha C.C. Monteiro de Castro G. Behavioural changes observed in demyelination model shares similarities with white matter abnormalities in humans. Behav. Brain Res. 2015 287 265 275 10.1016/j.bbr.2015.03.038 25843560
    [Google Scholar]
  105. Gloudina M.H. Mogamat S.H. Rajiv T.E. Tandi M. The haematological profile of patients with multiple sclerosis. 2012 http://www.scirp.org/journal/PaperInformation.aspx?PaperID=21173
    [Google Scholar]
  106. Akaishi T. Misu T. Fujihara K. Nakaya N. Nakamura T. Kogure M. Hatanaka R. Itabashi F. Kanno I. Takahashi T. Kuroda H. Fujimori J. Takai Y. Nishiyama S. Kaneko K. Ishii T. Aoki M. Nakashima I. Hozawa A. White blood cell count profiles in multiple sclerosis during attacks before the initiation of acute and chronic treatments. Sci. Rep. 2021 11 1 22357 10.1038/s41598‑021‑01942‑8 34785750
    [Google Scholar]
  107. Manoochehrabadi S. Arsang-Jang S. Mazdeh M. Inoko H. Sayad A. Taheri M. Analysis of STAT1, STAT2 and STAT3 mRNA expression levels in the blood of patients with multiple sclerosis. Hum. Antibodies 2019 27 2 91 98 10.3233/HAB‑180352 30412483
    [Google Scholar]
  108. Maiese K. Novel insights for multiple sclerosis and demyelinating disorders with apoptosis, autophagy, FoxO, and mTOR. Curr. Neurovasc. Res. 2021 18 2 169 171 10.2174/1567202618999210505124235 33964865
    [Google Scholar]
  109. Szalardy L. Zadori D. Tanczos E. Simu M. Bencsik K. Vecsei L. Klivenyi P. Elevated levels of PPAR-gamma in the cerebrospinal fluid of patients with multiple sclerosis. Neurosci. Lett. 2013 554 131 134 10.1016/j.neulet.2013.08.069 24021801
    [Google Scholar]
  110. Feinstein D.L. Galea E. Gavrilyuk V. Brosnan C.F. Whitacre C.C. Dumitrescu-Ozimek L. Landreth G.E. Pershadsingh H.A. Weinberg G. Heneka M.T. Peroxisome proliferator‐activated receptor‐γ agonists prevent experimental autoimmune encephalomyelitis. Ann. Neurol. 2002 51 6 694 702 10.1002/ana.10206 12112074
    [Google Scholar]
  111. Lebrun-Julien F. Bachmann L. Norrmén C. Trötzmüller M. Köfeler H. Rüegg M.A. Hall M.N. Suter U. Balanced mTORC1 activity in oligodendrocytes is required for accurate CNS myelination. J. Neurosci. 2014 34 25 8432 8448 10.1523/JNEUROSCI.1105‑14.2014 24948799
    [Google Scholar]
  112. Steelman A.J. Zhou Y. Koito H. Kim S. Payne H.R. Lu Q.R. Li J. Activation of oligodendroglial Stat3 is required for efficient remyelination. Neurobiol. Dis. 2016 91 336 346 10.1016/j.nbd.2016.03.023 27060559
    [Google Scholar]
  113. Kumar S. Mehan S. Narula A.S. Therapeutic modulation of JAK-STAT, mTOR, and PPAR-γ signaling in neurological dysfunctions. J. Mol. Med. (Berl.) 2023 101 1-2 9 49 10.1007/s00109‑022‑02272‑6 36478124
    [Google Scholar]
  114. Martins T.B. Rose J.W. Jaskowski T.D. Wilson A.R. Husebye D. Seraj H.S. Hill H.R. Analysis of proinflammatory and anti-inflammatory cytokine serum concentrations in patients with multiple sclerosis by using a multiplexed immunoassay. Am. J. Clin. Pathol. 2011 136 5 696 704 10.1309/AJCP7UBK8IBVMVNR 22031307
    [Google Scholar]
  115. Kallaur A.P. Oliveira S.R. Simão A.N.C. Alfieri D.F. Flauzino T. Lopes J. de Carvalho Jennings Pereira W.L. de Meleck Proença C. Borelli S.D. Kaimen-Maciel D.R. Maes M. Reiche E.M.V. Cytokine profile in patients with progressive multiple sclerosis and its association with disease progression and disability. Mol. Neurobiol. 2017 54 4 2950 2960 10.1007/s12035‑016‑9846‑x 27023227
    [Google Scholar]
  116. Brambilla R. The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol. 2019 137 5 757 783 10.1007/s00401‑019‑01980‑7 30847559
    [Google Scholar]
  117. Totuk Ö. Arsoy E. Türkoğlu R. Effects of neurocognitive rehabilitation on the levels of neurotransmitters and memory proteins in patients with multiple sclerosis. Experimed 2023 13 3 187 193 10.26650/experimed.1318122
    [Google Scholar]
  118. Akyuz E. Celik B.R. Aslan F.S. Sahin H. Angelopoulou E. Exploring the role of neurotransmitters in multiple sclerosis: An expanded review. ACS Chem. Neurosci. 2023 14 4 527 553 10.1021/acschemneuro.2c00589 36724132
    [Google Scholar]
  119. Moles L. Delgado S. Gorostidi-Aicua M. Sepúlveda L. Alberro A. Iparraguirre L. Suárez J.A. Romarate L. Arruti M. Muñoz-Culla M. Castillo-Triviño T. Otaegui D. international Multiple Sclerosis Microbiome Study Consortium Microbial dysbiosis and lack of SCFA production in a Spanish cohort of patients with multiple sclerosis. Front. Immunol. 2022 13 960761 10.3389/fimmu.2022.960761 36325343
    [Google Scholar]
  120. Melbye P. Olsson A. Hansen T.H. Søndergaard H.B. Bang Oturai A. Short-chain fatty acids and gut microbiota in multiple sclerosis. Acta Neurol. Scand. 2019 139 3 208 219 10.1111/ane.13045 30427062
    [Google Scholar]
  121. Saresella M. Marventano I. Barone M. La Rosa F. Piancone F. Mendozzi L. d’Arma A. Rossi V. Pugnetti L. Roda G. Casagni E. Cas M.D. Paroni R. Brigidi P. Turroni S. Clerici M. Alterations in circulating fatty acid are associated with gut microbiota dysbiosis and inflammation in multiple sclerosis. Front. Immunol. 2020 11 1390 10.3389/fimmu.2020.01390 32733460
    [Google Scholar]
  122. Martinez-Assucena A Marnetoft SU Rovira TR Hernandez-San-Miguel J Bernabeu M Martinell-Gispert-Sauch M Rehabilitation for multiple sclerosis in adults (I); Impairment and impact on functioning and quality of life: An overview. Crit Rev Phys Rehabil Med 2010 22 1-4 103 178 10.1615/CritRevPhysRehabilMed.v22.i1‑4.90
    [Google Scholar]
  123. Schreck L. Ryan S. Monaghan P. Cerebellum and cognition in multiple sclerosis. J. Neurophysiol. 2018 120 6 2707 2709 10.1152/jn.00245.2018
    [Google Scholar]
  124. Goudarzvand M. Choopani S. Shams A. Javan M. Khodaii Z. Ghamsari F. Naghdi N. Piryaei A. Haghparast A. Focal injection of ethidium bromide as a simple model to study cognitive deficit and its improvement. Basic Clin. Neurosci. 2016 7 1 63 72 27303601
    [Google Scholar]
/content/journals/cnsnddt/10.2174/0118715273336107241015100912
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Enhanced Neuroprotection in Experiment Multiple Sclerosis through Combined Rosiglitazone and Probiotic-Loaded Solid Lipid Nanoparticles: Modulation of Cellular Signaling Pathways
Bentham Science Publishers ; https://doi.org/10.2174/0118715273336107241015100912
/content/journals/cnsnddt/10.2174/0118715273336107241015100912
/content/journals/cnsnddt/10.2174/0118715273336107241015100912
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  • Article Type:     Research Article
Keywords: demyelination ; probiotics ; Multiple sclerosis ; oligodendrocytes ; nanoparticles ; rosiglitazone

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