Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Cassia tora Mitigates Aluminium Chloride Induced Alterations in Pro-inflammatory Cytokines, Neurotransmitters, and Beta-amyloid and Tau Protein Markers in Wistar Rats


Affiliations
1 Department of Zoology, Indira Gandhi National Tribal University, Amarkantak - 484887, Madhya Pradesh, India; pnm245@yahoo.com, India
2 Department of Zoology, Indira Gandhi National Tribal University, Amarkantak - 484887, Madhya Pradesh, India
3 Department of Horticulture, Aromatic and Medicinal Plants, Mizoram University, Aizawl - 796004, Mizoram, India
     

   Subscribe/Renew Journal


Background and Aim: Exposure to Aluminium (Al) has been reported to cause neurotoxicity in laboratory animals. Amyloid-β (Aβ) plaque formation, tau protein hyperphosphorylation, and neuroinflammation have been indicated as the possible mechanism of Al-induced neurodegeneration. The present study aimed to understand the mechanism of aluminium chloride (AlCl3)-induced neurotoxicity in Wistar rats and to assess the neuroprotective effect of methanolic extract of Cassia tora leaves (MECT). Material and Methods: Seventy-two male Wistar rats were randomly divided into nine groups. AlCl3 (100 mg/kg bw) and MECT (300 mg/kg bw) were given orally by gavage and memantine (MEM) was administered intraperitoneally (20 mg/kg bw) to rats, daily for 60 days. The spatial learning memory and recognition memory were evaluated using the Morris Water Maze (MWM) test. The levels of oxidative stress, neurotransmitter markers, pro-inflammatory markers, Aβ proteins plaques formation and tau protein hyperphosphorylation were evaluated. Histopathology of brain tissue was performed to assess the extent of tissue damage on AlCl3 exposure. Results: MECT significantly improved cognitive behaviours in AlCl3-exposed rats during the MWM test. Treatment with MECT resulted in a significant recovery of antioxidant enzyme function, the activity of neurotransmitter markers and pro-inflammatory cytokine levels. MECT prevented the aggregation of Aβ proteins and tau protein phosphorylation. Also, it inhibited the loss of neuronal integrity in the cortex and hippocampus regions of the brain in AlCl3-exposed rats. Conclusion: The findings demonstrate that a methanolic extract of Cassia tora leaves ameliorated AlCl3-induced neurodegeneration in Wistar rats.

Keywords

Aluminium Chloride, Beta-amyloid, Cassia tora, Neurotoxicity, Tau Protein.
User
Subscription Login to verify subscription
Notifications
Font Size

  • Rather MA, Justin-Thenmozhi A, Manivasagam T, Saravanababu C, Guillemin GJ, Essa MM. Asiatic Acid Attenuated Aluminum Chloride-Induced Tau Pathology, Oxidative Stress and Apoptosis Via AKT/ GSK-3β Signaling Pathway in Wistar Rats. Neurotox Res. 2019; 35(4):955-68. PMid: 30671870. https://doi. org/10.1007/s12640-019-9999-2
  • Cao Z, Wang P, Gao X, Shao B, Zhao S, Li Y. Lycopene attenuates aluminium-induced hippocampal lesions by inhibiting oxidative stress-mediated inflamma¬tion and apoptosis in the rat. J Inorg Biochem. 2019; 193:143-51. PMid: 30743053. https://doi.org/10.1016/j. jinorgbio.2019.01.017
  • Liu J, Wang Q, Sun X, Yang X, Zhuang C, Xu F, Cao Z, Li Y. The Toxicity of Aluminum Chloride on Kidney of Rats. Biol Trace Elem Res. 2016; 173(2):339-44. PMid: 26910335. https://doi.org/10.1007/s12011-016- 0648-9
  • Sadek KM, Lebda MA, Abouzed TK. The possible neuroprotective effects of melatonin in aluminum chlo¬ride-induced neurotoxicity via antioxidant pathway and Nrf2 signaling apart from metal chelation. Environ Sci Pollut Res. 2019; 26(9):9174-83. PMid: 30719664. https://doi.org/10.1007/s11356-019-04430-9
  • Hosseini SM, Hejazian LB, Amani R, Badeli NS. Geraniol attenuates oxidative stress, bioaccumulation, serological and histopathological changes during alumi¬num chloride-hepatopancreatic toxicity in male Wistar rats. Environ Sci Pollut Res. 2020; 27(16):20076-89. PMid: 32232762. https://doi.org/10.1007/s11356-020- 08128-1
  • Akinola BK, Olawuyi TS, Ukwenya VO, Daniel LD, Faleye BC. Protective effects of aloe vera gel (aloe baberdensis Miller) on aluminum chloride-induced reproductive toxicity in male wistar rats. JBRA Assist Reprod. 2021; 25(2):193-201. PMid: 33507720. https:// doi.org/10.5935/1518-0557.20200082
  • Turk E, Tekeli IO, Özkan H, Uyar A, Cellat M, Kuzu M, Yavas I, Yegani AA, Yaman T, Güvenç M. The protective effect of esculetin against aluminium chloride-induced reproductive toxicity in rats. Andrologia. 2020; 53(2):1- 13. PMid: 33368464. https://doi.org/10.1111/and.13930
  • Tair K, Kharoubi O, Taïr OA, Hellal N, Benyettou I, Aoues A. Aluminium-induced acute neurotoxicity in rats: Treatment with aqueous extract of Arthrophytum (Hammada scoparia). Journal of Acute Disease. 2016; 5(6):470-82. https://doi.org/10.1016/j.joad.2016.08.028
  • Ravi SK, Narasingappa RB, Mundagaru R, Girish TK, Vincent B. Cassia tora extract alleviates Aβ1-42 aggregation processes in vitro and protects against alu¬minium-induced neurodegeneration in rats. J Pharm Pharmacol. 2020; 72(8):1119-32. PMid: 32363579. https://doi.org/10.1111/jphp.13283
  • Mustafa HN. Neuro-amelioration of cinnamaldehyde in aluminum-induced Alzheimer’s disease rat model. J Histotechnol. 2020; 43(1):11-20. PMid: 31460853. https://doi.org/10.1080/01478885.2019.1652994
  • Bhargava VP, Netam AK, Singh R, Sharma P. Aluminium and Neuro-degeneration: Mechanism of pathogenesis and possible strategies for mitigation. Asian J Pharm Res Health Care. 2021; 13(1):101-14. https://doi. org/10.18311/ajprhc/2021/26174
  • Moneim AEA. Evaluating the potential role of pome¬granate peel in aluminum-induced oxidative stress and histopathological alterations in brain of female rats. Biol Trace Elem Res. 2012; 150(1-3):328-36. PMid: 22945624. https://doi.org/10.1007/s12011-012-9498-2
  • Khafaga AF. Exogenous phosphatidylcholine supple¬mentation retrieve aluminum-induced toxicity in male albino rats. Environ Sci Pollut Res. 2017; 24(18):15589- 98. PMid: 28523611. https://doi.org/10.1007/ s11356-017-9151-x
  • Briggs R, Kennelly SP, O’neill D. Drug treatments in Alzheimer’s disease. Clin Med. 2016; 16(3):247- 53. PMid: 27251914. https://doi.org/10.7861/ clinmedicine.16-3-247
  • Szeto JYY, Lewis SJG. Current Treatment Options for Alzheimer’s Disease and Parkinson’s Disease Dementia. Curr Neuropharmacol. 2016; 14(4):326-38. PMid: 26644155. https://doi.org/ 10.2174/1570159x146 66151208112754
  • Malabade R, Ashok T. Cassia tora a potential cogni¬tion enhancer in rats with experimentally induced Amnesia. J Young Pharm. 2015; 7(4):455-61. https://doi. org/10.5530/jyp.2015.4s.7
  • Bhandirge SK, Patel V, Patidar A, Pasi A, Sharma V. An overview on phytochemical and pharmacological profile of Cassia tora Linn. Int J Herb Med. 2016; 4(6): 50-55.
  • Bhargava VP, Netam, AK, Singh R, Sharma P. Identification of Phytochemicals of Cassia Tora by GC-MS and Correlation with reported Pharmacological Activities. Int J Biol Pharm Allied Sci. 2020; 9(12):3302- 12. https://doi.org/10.31032/IJBPAS/2020/9.12.5268
  • Justin-Thenmozhi A, Bharathi MD, Kiruthika R, Manivasagam T, Borah A, Essa MM. Attenuation of Aluminum Chloride-Induced Neuroinflammation and Caspase Activation Through the AKT/GSK-3β Pathway by Hesperidin in Wistar Rats. Neurotox Res. 2018; 34(3):463-76. PMid: 29687202. https://doi.org/10.1007/ s12640-018-9904-4
  • Abdel-aal RA, Assi AA, Kostandy BB. Memantine pre¬vents aluminum-induced cognitive deficit in rats. Behav Brain Res. 2011; 225(1):31-38. PMid: 21741993. https:// doi.org/10.1016/j.bbr.2011.06.031
  • Abulfadl YS, El-Maraghy NN, Ahmed AAE, Nofal S, Badary OA. Protective effects of thymoquinone on D-galactose and aluminum chloride induced neurotoxicity in rats: biochemical, histological and behavioral changes. Neurol Res. 2018; 40(4):324-33. PMid: 29464986. https://doi.org/10.1080/01616412.201 8.1441776
  • Ang HH, Lee KL. Analysis of mercury in Malaysian herbal preparations. J Med Biomed Res. 2005; 4(1):31- 36. https://doi.org/10.4314/jmbr.v4i1.10665
  • Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95(2):351-58. PMid: 36810. https://doi. org/10.1016/0003-2697(79)90738-3
  • Ellman GL. Tissue sulfhydryl Groups. Arch Biochem Biophys. 1959; 82(1):70-77. PMid: 13650640. https://doi. org/10.1016/0003-9861(59)90090-6
  • Kakkar P, Das B, Viswanathan PN. A modified spec¬trophotometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984; 21(2):130-32. PMID: 6490072.
  • Luck H. Catalase. Bergmeyer HU, editor. Methods of Enzymatic Analysis. New York: Academic Press; 1971. p. 885-93. https://doi.org/10.1016/B978-0-12-395630-9. X5001-4
  • Habig WH, Jakoby WB. Assays for differentiation of Glutathione-S-Transferases. Methods Enzymol. 1981; 77:398-405. PMid: 7329316. https://doi.org/10.1016/ s0076-6879(81)77053-8
  • Kumar A, Prakash A, Dogra S. Neuroprotective effect of carvedilol against aluminium induced toxicity: Possible behavioral and biochemical alterations in rats. Pharmacol Rep. 2011; 63(4):915-23. PMid: 22001979. https://doi.org/10.1016/s1734-1140(11)70607-7.
  • Gol M, Ghorbanian D, Soltanpour N, Faraji J, Pourghasem M. Protective effect of raisin (currant) against spatial memory impairment and oxidative stress in Alzheimer disease model. Nutr Neurosci. 2019; 22(2):110-18. PMid: 28812474. https://doi.org/10.1080/ 1028415X.2017.1354959
  • Khalaf NEA, El Banna FM, Youssef MY, Mosaad YM, Daba MHY, Ashour RH. Clopidogrel combats neu¬roinflammation and enhances learning behavior and memory in a rat model of Alzheimer’s disease. Pharmacol Biochem Behav. 2020; 195:1-9. PMid: 32474163. https://doi.org/10.1016/j.pbb.2020.172956
  • Auti ST, Kulkarni YA. Neuroprotective effect of car¬damom oil against aluminum induced neurotoxicity in rats. Front Neurol. 2019; 10:1-17. PMid: 31114535. https://doi.org/10.3389/fneur.2019.00399
  • Deng Z, Coudray C, Gouzoux L, Mazur A, Rayssiguier Y, Pippin D. Effect of Oral Aluminum and Aluminum Citrate on Blood Level and Short-Term Tissue Distribution of Aluminum in the Rat. Biol Trace Elem Res. 1998; 63(2):139-47. PMid: 9823440. https://doi. org/10.1007/BF02778873
  • Skalny AV, Aschner M, Jiang Y, Gluhcheva YG, Tizabi Y, Lobinski R, Tinkov AA. Molecular mechanisms of aluminum neurotoxicity: Update on adverse effects and therapeutic strategies. Aschner M, Costa LG, editors. Advances in Neurotoxicology Neurotoxicity of Metals: Old Issues and New Developments. Massachusetts, Academic Press; 2021. p. 1-34. https://doi.org/10.1016/ bs.ant.2020.12.001
  • Ighodaro OM, Akinloye OA. First line defence anti¬oxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med. 2018; 54(4):287-93. https://doi.org/10.1016/j. ajme.2017.09.001
  • Nandi A, Yan LJ, Jana CK, Das N. Role of catalase in oxidative stress-and age-associated degenerative diseases. Oxid Med Cell Longev. 2019; 2019:1-19. PMid: 31827713. https://doi.org/10.1155/2019/9613090
  • Justin-Thenmozhi AJ, Raja TRW, Janakiraman U, Manivasagam T. Neuroprotective Effect of Hesperidin on Aluminium Chloride Induced Alzheimer’s Disease in Wistar Rats. Neurochem Res. 2015; 40(4):767-76. PMid: 25630717. https://doi.org/10.1007/s11064-015- 1525-1
  • Hussien HM, Abd-Elmegied A, Ghareeb DA, Hafez HS, Ahmed HEA, El-moneam NA. Neuroprotective effect of berberine against environmental heavy metals-induced neurotoxicity and Alzheimer’s-like disease in rats. Food Chem Toxicol. 2018; 111:432-44. PMid: 29170048. https://doi.org/10.1016/j.fct.2017.11.025
  • Sharma P., Firdous S, Singh R. Neurotoxic effect of cypermethrin and protective role of resveratrol in Wistar rats. Int J Nutr Pharmacol Neurol Dis. 2014; 4(2):104- 11. https://doi.org/ 10.4103/2231-0738.129598
  • Behl T, Kaur D, Sehgal A, Singh S, Sharma N, Zengin G, Andronie-Cioara FL, Toma MM, Bungau S, Bumbu AG. Role of monoamine oxidase activity in alzheimer’s disease: An insight into the therapeutic potential of inhib¬itors. Molecules. 2021; 26(12):1-21. PMid: 34207264. https://doi.org/10.3390/molecules26123724
  • Liu L, Liu Y, Zhao J, Xing X, Zhang C, Meng H. Neuroprotective Effects of D-(-)-Quinic Acid on Aluminum Chloride-Induced Dementia in Rats. Evid Based Complement Alternat Med. 2020; 2020:1-10. PMid: 32454864. https://doi.org/10.1155/2020/5602597
  • Abd el-Rady NM, Ahmed A, Abdel-Rady MM, Ismail OI. Glucagon-like peptide-1 analog improves neuronal and behavioral impairment and promotes neuropro¬tection in a rat model of aluminum-induced dementia. Physiol Rep. 2021; 8(24):1-13. PMid: 33355990. https:// doi.org/10.14814/phy2.14651
  • Alasmari F, Alshammari MA, Alasmari AF, Alanazi WA, Alhazzani K. Neuroinflammatory Cytokines Induce Amyloid Beta Neurotoxicity through Modulating Amyloid Precursor Protein Levels/Metabolism. BioMed Res Int. 2018; 2018:1-8. PMid: 30498753. https://doi. org/10.1155/2018/3087475
  • Monteiro S, Roque S, Marques F, Correia-Neves M, Cerqueira JJ. Brain interference: Revisiting the role of IFN-γ in the central nervous system. Prog Neurobiol. 2017; 156:149-63. PMid: 28528956. https://doi. org/10.1016/j.pneurobio.2017.05.003
  • Qiu T, Liu Q, Chen Y, Zhao Y, Li Y. Aβ42 and Aβ40: similarities and differences. J Pept Sci. 2015; 21(7):522- 29. PMid: 26018760. https://doi.org/10.1002/psc.2789
  • Khalifa M, Safar MM, Abdelsalam RM, Zaki HF. Telmisartan Protects Against Aluminum-Induced Alzheimer-like Pathological Changes in Rats. Neurotox Res. 2020; 37(2):275-85. PMid: 31332715. https://doi. org/10.1007/s12640-019-00085-z
  • Promyo K, Iqbal F, Chaidee N, Chetsawang B. Aluminum chloride-induced amyloid β accumula¬tion and endoplasmic reticulum stress in rat brain are averted by melatonin. Food Chem Toxicol. 2020; 146:1-9. PMid: 33130240. https://doi.org/10.1016/j. fct.2020.111829
  • Liu J, Chang L, Song Y, Li H, Wu Y. The role of NMDA receptors in Alzheimer’s disease. Front Neurosci. 2019; 13:1-22. PMid: 30800052. https://doi.org/10.3389/ fnins.2019.00043
  • Mondragon-Rodriguez S, Perry G, Zhu X, Boehm J. Amyloid beta and tau proteins as therapeutic targets for Alzheimer’s disease treatment: Rethinking the cur¬rent strategy. Int J Alzheimer’s Dis. 2012; 2012:1-7. PMid: 22482074. https://doi.org/10.1155/2012/630182
  • Shukla SK, Kumar A, Terrence M, Yusuf J, Singh VP, Mishra M. The Probable Medicinal Usage of Cassia tora: An Overview. OnLine J Biol Sci. 2013; 13(1):13- 17. https://doi.org/10.3844/ojbssp.2013.13.17
  • Arya V, Yadav JP. Antioxidant activity and total phenolics in leaves extracts of Cassia tora L. Pharmacologyonline. 2010; 2: 1030-36.
  • Khalifeh M, Barreto GE, Sahebkar A. Therapeutic potential of trehalose in neurodegenerative diseases: The knowns and unknowns. Neural Regen Res. 2021; 16(10):2026-27. PMid: 33642389. https://doi. org/10.4103/1673-5374.308085
  • Holler CJ, Taylor G, McEachin ZT, Deng Q, Watkins WJ, Hudson K, Easley CA, Hu WT, Hales CM, Rossoll W, Bassell GJ, Kukar T. Trehalose upregulates progran¬ulin expression in human and mouse models of GRN haploinsufficiency: A novel therapeutic lead to treat frontotemporal dementia. Mol Neurodegener. 2016; 11(1):1-17. PMid: 27341800. https://doi.org/10.1186/ s13024-016-0114-3
  • Sathya S, Shanmuganathan B, Saranya S, Vaidevi S, Ruckmani K, Devi KP. Phytol-loaded PLGA nanopar¬ticle as a modulator of Alzheimer’s toxic Aβ peptide aggregation and fibrillation associated with impaired neuronal cell function. Artif Cells Nanomed Biotechnol. 2018; 46(8):1719-30. PMid: 29069924. https://doi.org/1 0.1080/21691401.2017.1391822
  • Grimm MOW, Mett J, Hartmann T. The impact of Vitamin E and other fat-soluble vitamins on Alzheimer’s disease. Int J Mol Sci. 2016; 17(11):1-18. PMid: 27792188. https://doi.org/10.3390/ijms17111785
  • Yamamuro Y, Yamaguchi Y, Abe S, Takenaga F. Neurochemical and behavioural impact of C18 fatty acids in male mice postweaning. Exp Biol Med. 2013; 238(6):658-67. PMid: 23918877. https://doi. org/10.1177/1535370213489451
  • Khalaf SS, Hafez MM, Mehanna ET, Mesbah NM, Abo-Elmatty DM. Combined vildagliptin and meman¬tine treatment downregulates expression of amyloid precursor protein, and total and phosphorylated tau in a rat model of combined Alzheimer’s disease and type 2 diabetes. Naunyn Schmiedeberg’s Arch Pharmacol. 2019; 392(6):685-95. PMid: 30759264. https://doi. org/10.1007/s00210-019-01616-3
  • Babu SM, Swain S, Boyapati P. Neuroprotective activity of ethanolic extract of Tamarindus indica seeds against aluminium induced neurotoxicity. Asian J Pharm Hea Sci. 2016; 6(2):1445-52.
  • Liu W, Xu Z, Deng Y, Xu B, Wei Y, Yang T. Protective effects of memantine against methylmercury-induced glutamate dyshomeostasis and oxidative stress in rat cerebral cortex. Neurotox Res. 2013; 24(3):320-37. PMid: 23504438. https://doi.org/10.1007/s12640-013- 9386-3
  • Eldeeb AA, Fathy AE, Elgendy SA. Differential potency of vitamin D3, folic acid and memantine in protecting against neurobehavioral alterations of sco¬polamine induced Alzheimer’s model in rats. Int J Basic Clin Pharmacol. 2021; 10(5):471-78. https://doi. org/10.18203/2319-2003.ijbcp20211638
  • Gothwal A, Kumar H, Nakhate KT, Ajazuddin Dutta A, Borah A, Gupta U. Lactoferrin Coupled Lower Generation PAMAM Dendrimers for Brain Targeted Delivery of Memantine in Aluminum-Chloride-Induced Alzheimer’s Disease in Mice. Bioconjug Chem. 2019; 30(10):2573-83. PMid: 31553175. https://doi. org/10.1021/acs.bioconjchem.9b00505
  • Onogi H, Ishigaki S, Nakagawasai O, Arai-Kato Y, Arai Y, Watanabe H, Miyamoto A, Tan-No K, Tadano T. Influence of memantine on brain monoaminergic neu¬rotransmission parameters in mice: Neurochemical and behavioral study. Biol Pharm Bull. 2009; 32(5):850-55. PMid: 19420753. https://doi.org/10.1248/bpb.32.850
  • Shata A, Elkashef W, Hamouda MA, Eissa H. Effect of Artesunate vs Memantine in Aluminum Chloride Induced Model of Neurotoxicity in Rats. Adv Alzheimer’s Dis. 2020; 09(1):1-19. https://doi.org/10.4236/ aad.2020.91001

Abstract Views: 89

PDF Views: 0




  • Cassia tora Mitigates Aluminium Chloride Induced Alterations in Pro-inflammatory Cytokines, Neurotransmitters, and Beta-amyloid and Tau Protein Markers in Wistar Rats

Abstract Views: 89  |  PDF Views: 0

Authors

Vikas Pankaj Bhargava
Department of Zoology, Indira Gandhi National Tribal University, Amarkantak - 484887, Madhya Pradesh, India; pnm245@yahoo.com, India
Aashish Kumar Netam
Department of Zoology, Indira Gandhi National Tribal University, Amarkantak - 484887, Madhya Pradesh, India
Rambir Singh
Department of Horticulture, Aromatic and Medicinal Plants, Mizoram University, Aizawl - 796004, Mizoram, India
Poonam Sharma
Department of Zoology, Indira Gandhi National Tribal University, Amarkantak - 484887, Madhya Pradesh, India

Abstract


Background and Aim: Exposure to Aluminium (Al) has been reported to cause neurotoxicity in laboratory animals. Amyloid-β (Aβ) plaque formation, tau protein hyperphosphorylation, and neuroinflammation have been indicated as the possible mechanism of Al-induced neurodegeneration. The present study aimed to understand the mechanism of aluminium chloride (AlCl3)-induced neurotoxicity in Wistar rats and to assess the neuroprotective effect of methanolic extract of Cassia tora leaves (MECT). Material and Methods: Seventy-two male Wistar rats were randomly divided into nine groups. AlCl3 (100 mg/kg bw) and MECT (300 mg/kg bw) were given orally by gavage and memantine (MEM) was administered intraperitoneally (20 mg/kg bw) to rats, daily for 60 days. The spatial learning memory and recognition memory were evaluated using the Morris Water Maze (MWM) test. The levels of oxidative stress, neurotransmitter markers, pro-inflammatory markers, Aβ proteins plaques formation and tau protein hyperphosphorylation were evaluated. Histopathology of brain tissue was performed to assess the extent of tissue damage on AlCl3 exposure. Results: MECT significantly improved cognitive behaviours in AlCl3-exposed rats during the MWM test. Treatment with MECT resulted in a significant recovery of antioxidant enzyme function, the activity of neurotransmitter markers and pro-inflammatory cytokine levels. MECT prevented the aggregation of Aβ proteins and tau protein phosphorylation. Also, it inhibited the loss of neuronal integrity in the cortex and hippocampus regions of the brain in AlCl3-exposed rats. Conclusion: The findings demonstrate that a methanolic extract of Cassia tora leaves ameliorated AlCl3-induced neurodegeneration in Wistar rats.

Keywords


Aluminium Chloride, Beta-amyloid, Cassia tora, Neurotoxicity, Tau Protein.

References





DOI: https://doi.org/10.18311/ti%2F2023%2Fv30i1%2F30863