Neuroinflammatory Response and Redox-regulation Activity of Hyperoside in Manganese-induced Neurotoxicity Model of Wistar Rats


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Abstract

Background:Excessive manganese exposure can lead to neurotoxicity with detrimental effects on the brain. Neuroinflammatory responses and redox regulation play pivotal roles in this process. Exploring the impact of hyperoside in a Wistar rat model offers insights into potential neuroprotective strategies against manganese-induced neurotoxicity.

Objective:The study investigated the neuroprotective efficacy of hyperoside isolated from the ethanol leaf extract of Gongronema latifolium (HELEGL), in the brain tissue of Wistar rats following 15 consecutive days of exposure to 30 mg/L of MnCl2.

Methods:Control animals in Group 1 had access to regular drinking water, while animals in groups 2–4 were exposed to MnCl2 in their drinking water. Groups 3 and 4 also received additional HELEGL at doses of 100 mg/kg and 200 mg/kg of body weight, respectively. In Group 5, HELEGL at a dose of 100 mg/kg of body weight was administered alone. Treatment with HELEGL commenced on day 8 via oral administration.

Results:HELEGL effectively mitigated MnCl2-induced memory impairment, organ-body weight discrepancies, and fluid intake deficits. Exposure to MnCl2 increased the activities or levels of various markers such as acyl peptide hydrolase, tumour necrosis factor-α, dipeptidyl peptidase IV, nitric oxide, IL-1β, prolyl oligopeptidase, caspase-3, myeloperoxidase, H2O2, and malondialdehyde, while it decreased the activities or levels of others, including AChE, BChE, DOPA, serotonin, epinephrine, norepinephrine, GST, GPx, CAT, SOD, GSH, and T-SH (p < 0.05). In contrast, HELEGL effectively counteracted the adverse effects of MnCl2 by alleviating oxidative stress, inflammation, apoptosis, mitochondrial dysfunction, cognitive deficits, and bolstering the antioxidant status. Moreover, HELEGL restored the normal histoarchitecture of the brain, which had been distorted by MnCl2.

Conclusion:In summary, HELEGL reversed the causative factors of neurodegenerative diseases induced by MnCl2 exposure, suggesting its potential for further exploration as a prospective therapeutic agent in the management of Alzheimer's disease and related forms of dementia.

About the authors

Olalekan Ogunro

Department of Biological Sciences, Reproductive & Endocrinology, Toxicology, and Bioinformatics Research Laboratory, Koladaisi University

Author for correspondence.
Email: info@benthamscience.net

Oluwaseun Olasehinde

Department of Biochemistry, University of Ilorin

Email: info@benthamscience.net

References

  1. Chen P, Bornhorst J, Aschner M. Manganese metabolism in humans. FBL 2018; 23(9): 1655-79. doi: 10.2741/4665
  2. Horning KJ, Caito SW, Tipps KG, Bowman AB, Aschner M. Manganese is essential for neuronal health. Annu Rev Nutr 2015; 35(1): 71-108. doi: 10.1146/annurev-nutr-071714-034419 PMID: 25974698
  3. Miah MR, Ijomone OM, Okoh COA, Ijomone OK, Akingbade GT, Ke T, et al. The effects of manganese overexposure on brain health. Neurochem Int 2019; 2020: 135. PMID: 31972215
  4. Soares ATG, Silva AC, Tinkov AA, et al. The impact of manganese on neurotransmitter systems. J Trace Elem Med Biol 2020; 61: 126554. doi: 10.1016/j.jtemb.2020.126554 PMID: 32480053
  5. Kevadiya BD, Ottemann BM, Thomas MB, et al. Neurotheranostics as personalized medicines. Adv Drug Deliv Rev 2019; 148: 252-89. doi: 10.1016/j.addr.2018.10.011 PMID: 30421721
  6. Rai SN, Mishra D, Singh P, Vamanu E, Singh MP. Therapeutic applications of mushrooms and their biomolecules along with a glimpse of in silico approach in neurodegenerative diseases. Biomed Pharmacother 2021; 137: 111377. doi: 10.1016/j.biopha.2021.111377 PMID: 33601145
  7. Nwanna EE, Adebayo AA, Oboh G, Ogunsuyi OB, Ademosun AO. Modulatory effects of alkaloid extract from Gongronema latifolium (Utazi) and Lasianthera africana (Editan) on activities of enzymes relevant to neurodegeneration. J Diet Suppl 2019; 16(1): 27-39. doi: 10.1080/19390211.2018.1426075 PMID: 29451813
  8. Cenini G, Lloret A, Cascella R. Oxidative stress in neurodegenerative diseases: From a mitochondrial point of view. Oxid Med Cell Longev 2019; 2019: 2105607.
  9. Javaid SF, Giebel C, Khan MAB, Hashim MJ. Epidemiology of Alzheimer’s disease and other dementias: rising global burden and forecasted trends version 1; peer review: 1 approved with reservations. F1000 Research 2021; 10: 425.
  10. Iriti M, Vitalini S, Fico G, Faoro F. Neuroprotective herbs and foods from different traditional medicines and diets. Molecules 2010; 15(5): 3517-55. doi: 10.3390/molecules15053517 PMID: 20657497
  11. Ayeni EA, Gong Y, Yuan H, Hu Y, Bai X, Liao X. Medicinal plants for anti-neurodegenerative diseases in West Africa. J Ethnopharmacol 2022; 285: 114468. doi: 10.1016/j.jep.2021.114468 PMID: 34390796
  12. e B, e B, N O, A M, Djobissie SFA. Gongronema latifolium: A phytochemical, nutritional and pharmacological review. J Physiol Pharmacol 2016; 6(1): 811-24. doi: 10.5455/jppa.1969123104000
  13. Gyebi GA, Ejoh JC, Ogunyemi OM, et al. Probing the multitargeting potential of n-hexane fraction of Gongronema latifolium leaves in neurodegeneration viain vitro, GC–MS and in silico studies. Future J Pharm Sci 2023; 9(1): 84. doi: 10.1186/s43094-023-00536-7
  14. Gyebi GA, Ogunyemi OM, Ibrahim IM, et al. Identification of potential inhibitors of cholinergic and β-secretase enzymes from phytochemicals derived from Gongronema latifolium Benth leaf: An integrated computational analysis. Mol Divers 2023. doi: 10.1007/s11030-023-10658-y PMID: 37338673
  15. Imo C, Uhegbu F. Phytochemical Analysis of Gongronema latifolium (Benth) leaf using gas phytochemical analysis of Gongronema latifolium benth leaf using gas chromatographic flame ionization detector. Int J Chem Biomol Sci 2015; 1(2): 60-8.
  16. Raza A, Xu X, Sun H, Tang J, Ouyang Z. Pharmacological activities and pharmacokinetic study of hyperoside: A short review. Trop J Pharm Res 2017; 16(2): 483-9. doi: 10.4314/tjpr.v16i2.30
  17. Xu S, Chen S, Xia W, Sui H, Fu X. Hyperoside: A review of its structure, synthesis, pharmacology, pharmacokinetics and toxicity. Molecules 2022; 27(9): 3009. doi: 10.3390/molecules27093009
  18. Cho M, Kang IJ, Won MH, Lee HS, You S. The antioxidant properties of ethanol extracts and their solvent-partitioned fractions from various green seaweeds. J Med Food 2010; 13(5): 1232-9. doi: 10.1089/jmf.2010.1124 PMID: 20828323
  19. He J, Li H, Li G, Yang L. Hyperoside protects against cerebral ischemia-reperfusion injury by alleviating oxidative stress, inflammation and apoptosis in rats. Biotechnol Biotechnol Equip 2019; 33(1): 798-806. doi: 10.1080/13102818.2019.1620633
  20. Al-Hindi B, Yusoff NA, Ahmad M, et al. Safety assessment of the ethanolic extract of Gongronema latifolium Benth. leaves: A 90-day oral toxicity study in Sprague Dawley rats. BMC Complement Altern Med 2019; 19(1): 152. doi: 10.1186/s12906-019-2573-x PMID: 31253153
  21. Adedara IA, Abolaji AO, Awogbindin IO, Farombi EO. Suppression of the brain-pituitary-testicular axis function following acute arsenic and manganese co-exposure and withdrawal in rats. J Trace Elem Med Biol 2017; 39: 21-9. doi: 10.1016/j.jtemb.2016.07.001 PMID: 27908416
  22. Ogunro OB, Salawu AO, Alotaibi SS, Albogami SM, Batiha GES, Waard MD. Quercetin-3-O-β-d-glucopyranoside-rich fraction from Spondias mombin leaves halted responses from oxidative stress, neuroinflammation, apoptosis, and lipid peroxidation in the brain of dichlorvos-treated wistar rats. Toxics 2022; 10(8): 477. doi: 10.3390/toxics10080477 PMID: 36006156
  23. Ogunro OB. Redox-regulation and anti-inflammatory system activation by quercetin-3-O- β - D -glucopyranoside-rich fraction from Spondias mombin leaves : biochemical, reproductive and histological study in rat model of dichlorvos toxicity. RPSPPR 2023; 2(4): 1-19.
  24. Wolff SP. Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Methods Enzymol 1994; 233(C): 182-9. doi: 10.1016/S0076-6879(94)33021-2
  25. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82: 70-7.
  26. Buege JA, Aust SD. Biomembranes - Part C: Biological oxidations. Methods Enzymol 1978; 52: 302-10. doi: 10.1016/S0076-6879(78)52032-6 PMID: 672633
  27. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and 15Nnitrate in biological fluids. Anal Biochem 1982; 126(1): 131-8. doi: 10.1016/0003-2697(82)90118-X PMID: 7181105
  28. Granell S, Gironella M, Bulbena O, et al. Heparin mobilizes xanthine oxidase and induces lung inflammation in acute pancreatitis. Crit Care Med 2003; 31(2): 525-30. doi: 10.1097/01.CCM.0000049948.64660.06 PMID: 12576961
  29. Ellman GL, Courtney KD, Andres V Jr, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7(2): 88-95. doi: 10.1016/0006-2952(61)90145-9 PMID: 13726518
  30. Richards PG, Johnson MK, Ray DE. Identification of acylpeptide hydrolase as a sensitive site for reaction with organophosphorus compounds and a potential target for cognitive enhancing drugs. Mol Pharmacol 2000; 58(3): 577-83. doi: 10.1124/mol.58.3.577 PMID: 10953051
  31. Cahlíková L, Hulová L, Hrabinová M, et al. Isoquinoline alkaloids as prolyl oligopeptidase inhibitors. Fitoterapia 2015; 103: 192-6. doi: 10.1016/j.fitote.2015.04.004 PMID: 25863351
  32. Pagel P, Blome J, Wolf HU. High-performance liquid chromatographic separation and measurement of various biogenic compounds possibly involved in the pathomechanism of Parkinson’s disease. J Chromatogr, Biomed Appl 2000; 746(2): 297-304. doi: 10.1016/S0378-4347(00)00348-0 PMID: 11076082
  33. Habig WH, Jakoby WB. Assays for differentiation of glutathione S-Transferases. Methods Enzymol 1981; 77(C): 398-405. doi: 10.1016/S0076-6879(81)77053-8 PMID: 7329316
  34. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical role as a component of glutathione peroxidase. Science 1973; 179(4073): 588-90. doi: 10.1126/science.179.4073.588 PMID: 4686466
  35. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105(C): 121-6. doi: 10.1016/S0076-6879(84)05016-3 PMID: 6727660
  36. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247(10): 3170-5. doi: 10.1016/S0021-9258(19)45228-9 PMID: 4623845
  37. Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 1974; 11(3): 151-69. doi: 10.1159/000136485 PMID: 4831804
  38. Lowry O, Rosebrough N, Farr AL, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75. doi: 10.1016/S0021-9258(19)52451-6 PMID: 14907713
  39. Yong LCJ. The Theory and Practice of Histological Techniques. Pathology 1992; Vol. 24
  40. Balachandran RC, Mukhopadhyay S, McBride D, et al. Brain manganese and the balance between essential roles and neurotoxicity. J Biol Chem 2020; 295(19): 6312-29. doi: 10.1074/jbc.REV119.009453 PMID: 32188696
  41. Avila DS, Puntel RL, Aschner M. Manganese in health and disease. Met Ions Life Sci 2013; 13: 199-227. doi: 10.1007/978-94-007-7500-8_7 PMID: 24470093
  42. Kwakye G, Paoliello M, Mukhopadhyay S, Bowman A, Aschner M. Manganese-induced parkinsonism and Parkinson’s disease: Shared and distinguishable features. Int J Environ Res Public Health 2015; 12(7): 7519-40. doi: 10.3390/ijerph120707519 PMID: 26154659
  43. Harischandra DS, Ghaisas S, Zenitsky G, et al. Manganese-induced neurotoxicity: New insights into the triad of protein misfolding, mitochondrial impairment, and neuroinflammation. Front Neurosci 2019; 13(JUN): 654. doi: 10.3389/fnins.2019.00654 PMID: 31293375
  44. Park JY, Han X, Piao MJ, Oh MC, Madushan P, Jayatissa D. Hyperoside induces endogenous antioxidant system to alleviate oxidative stress. J Cancer Prev 2016; 21(1): 41-7.
  45. Nadeem RI, Ahmed HI, El-Sayeh BM. Protective effect of vinpocetine against neurotoxicity of manganese in adult male rats. Naunyn Schmiedebergs Arch Pharmacol 2018; 391(7): 729-42. doi: 10.1007/s00210-018-1498-0 PMID: 29671021
  46. Patyar S, Prakash A, Modi M, Medhi B. Role of vinpocetine in cerebrovascular diseases. Pharmacol Rep 2011; 63(3): 618-28. doi: 10.1016/S1734-1140(11)70574-6 PMID: 21857073
  47. Abu-Elfotuh K, Hamdan AME, Mohammed AA, et al. Neuroprotective effects of some nutraceuticals against manganese-induced parkinson’s disease in rats: Possible modulatory effects on TLR4/NLRP3/NF-κB, GSK-3β, Nrf2/HO-1, and apoptotic pathways. Pharmaceuticals 2022; 15(12): 1554. doi: 10.3390/ph15121554 PMID: 36559006
  48. Daniela M, Catalina L, Ilie O, Paula M, Daniel-Andrei I, Ioana B. Effects of exercise training on the autonomic nervous system with a focus on anti-inflammatory and antioxidants effects. Antioxidants 2022; 11(2): 350. doi: 10.3390/antiox11020350 PMID: 35204231
  49. Švob Štrac D, Pivac N, Mück-Šeler D. The serotonergic system and cognitive function. Transl Neurosci 2016; 7(1): 35-49. doi: 10.1515/tnsci-2016-0007 PMID: 28123820
  50. Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase inhibitors: Pharmacology and toxicology. Curr Neuropharmacol 2013; 11(3): 315-35. doi: 10.2174/1570159X11311030006 PMID: 24179466
  51. Angelopoulou E, Piperi C. DPP-4 inhibitors: A promising therapeutic approach against Alzheimer’s disease. Ann Transl Med 2018; 6(12): 255-5. doi: 10.21037/atm.2018.04.41 PMID: 30069457
  52. Yang L, Han W, Luo Y, et al. Adapentpronitrile, a new dipeptidyl peptidase-IV inhibitor, ameliorates diabetic neuronal injury through inhibiting mitochondria-related oxidative stress and apoptosis. Front Cell Neurosci 2018; 12(July): 214. doi: 10.3389/fncel.2018.00214 PMID: 30072873
  53. Zolotov NN, Schepetkin IA, Voronina TA, et al. Therapeutic effect of novel cyanopyrrolidine-based prolyl oligopeptidase inhibitors in rat models of amnesia. Front Chem 2021; 9(December): 780958. doi: 10.3389/fchem.2021.780958 PMID: 35004610
  54. Eteläinen T, Kulmala V, Svarcbahs R, Jäntti M, Myöhänen TT. Prolyl oligopeptidase inhibition reduces oxidative stress via reducing NADPH oxidase activity by activating protein phosphatase 2A. Free Radic Biol Med 2021; 169(March): 14-23. doi: 10.1016/j.freeradbiomed.2021.04.001 PMID: 33838285
  55. Chen G, Xu T, Yan Y, et al. Amyloid beta: Structure, biology and structure-based therapeutic development. Acta Pharmacol Sin 2017; 38(9): 1205-35. doi: 10.1038/aps.2017.28 PMID: 28713158
  56. Castorina A, Al-Badri G, Leggio GM, Musumeci G, Marzagalli R, Drago F. Tackling dipeptidyl peptidase IV in neurological disorders. Neural Regen Res 2018; 13(1): 26-34. doi: 10.4103/1673-5374.224365 PMID: 29451201
  57. Ayaz M, Ullah F, Sadiq A, Kim MO, Ali T. Editorial: Natural products-based drugs: Potential therapeutics against Alzheimer’s disease and other neurological disorders. Front Pharmacol 2019; 10(November): 1417. doi: 10.3389/fphar.2019.01417 PMID: 31849668
  58. Shao S, Xu Q, Yu X, Pan R, Chen Y. Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions. Pharmacol Ther 2020; 209: 107503. doi: 10.1016/j.pharmthera.2020.107503 PMID: 32061923
  59. Srinivasan V, Korhonen L, Lindholm D. The unfolded protein response and autophagy as drug targets in neuropsychiatric disorders. Front Cell Neurosci 2020; 14(September): 554548. doi: 10.3389/fncel.2020.554548 PMID: 33132844
  60. Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: Current state. Nutr J 2015; 15(1): 71. doi: 10.1186/s12937-016-0186-5 PMID: 27456681
  61. Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex J Med 2018; 54(4): 287-93. doi: 10.1016/j.ajme.2017.09.001
  62. Singh A, Kukreti R, Saso L, Kukreti S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules 2019; 24(8): 1583. doi: 10.3390/molecules24081583 PMID: 31013638
  63. Huang Y, Wen Q, Huang J, et al. Manganese (II) chloride leads to dopaminergic neurotoxicity by promoting mitophagy through BNIP3-mediated oxidative stress in SH-SY5Y cells. Cell Mol Biol Lett 2021; 26(1): 23. doi: 10.1186/s11658-021-00267-8 PMID: 34078255
  64. Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis 2013; 3(4): 461-91. doi: 10.3233/JPD-130230 PMID: 24252804
  65. Behl T, Makkar R, Sehgal A, et al. Current trends in neurodegeneration: Cross talks between oxidative stress, cell death, and inflammation. Int J Mol Sci 2021; 22(14): 7432. doi: 10.3390/ijms22147432 PMID: 34299052
  66. Perry SW, Dewhurst S, Bellizzi MJ, Gelbard HA. Tumor necrosis factor-alpha in normal and diseased brain: Conflicting effects via intraneuronal receptor crosstalk? J Neurovirol 2002; 8(6): 611-24. doi: 10.1080/13550280290101021 PMID: 12476354
  67. Rothaug M, Becker-Pauly C, Rose-John S. The role of interleukin-6 signaling in nervous tissue. Biochim Biophys Acta Mol Cell Res 2016; 1863(6): 1218-27. doi: 10.1016/j.bbamcr.2016.03.018 PMID: 27016501
  68. Chen S, Chen H, Du Q, Shen J. Targeting myeloperoxidase (MPO) mediated oxidative stress and inflammation for reducing brain ischemia injury: Potential application of natural compounds. Front Physiol 2020; 11(May): 433. doi: 10.3389/fphys.2020.00433 PMID: 32508671
  69. Picón-Pagès P, Garcia-Buendia J, Muñoz FJ. Functions and dysfunctions of nitric oxide in brain. Biochim Biophys Acta Mol Basis Dis 2019; 1865(8): 1949-67. doi: 10.1016/j.bbadis.2018.11.007 PMID: 30500433
  70. Morgan CW, Julien O, Unger EK, Shah NM, Wells JA. Turning on caspases with genetics and small molecules Internet. In: Methods in Enzymology. (1st ed.). Elsevier Inc 2014; 544: pp. 179-213. doi: 10.1016/B978-0-12-417158-9.00008-X
  71. Mohammadi M, Gozashti MH, Aghadavood M, Mehdizadeh MR, Hayatbakhsh MM. Clinical significance of serum IL-6 and TNF-α levels in patients with metabolic syndrome. Rep Biochem Mol Biol 2017; 6(1): 74-9. PMID: 29090232
  72. Pall M. The NO/ONOO-cycle as the central cause of heart failure. Int J Mol Sci 2013; 14(11): 22274-330. doi: 10.3390/ijms141122274 PMID: 24232452
  73. Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007; 87(1): 315-424. doi: 10.1152/physrev.00029.2006 PMID: 17237348
  74. Trujillo M, Ferrer-Sueta G, Radi R. Kinetic studies on peroxynitrite reduction by peroxiredoxins. Methods Enzymol 2008; 441(08): 173-96. doi: 10.1016/S0076-6879(08)01210-X PMID: 18554535
  75. Kumar A, Chen SH, Kadiiska MB, et al. Inducible nitric oxide synthase is key to peroxynitrite-mediated, LPS-induced protein radical formation in murine microglial BV2 cells. Free Radic Biol Med 2014; 73: 51-9. doi: 10.1016/j.freeradbiomed.2014.04.014 PMID: 24746617
  76. Su L, Zhang J, Gomez H, et al. Review article reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev 2019; 5080843.
  77. Galluzzi L, Vitale I, Aaronson SA, et al. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Differ 2018; 25(3): 486-541. doi: 10.1038/s41418-017-0012-4 PMID: 29362479

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