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Protection of prefrontal cortex neurons and improvement of memory in epileptic rats by 1-triacontanol cerotate

Year 2024, Volume: 28 Issue: 5, 1572 - 1580, 28.06.2025

Abstract

Epilepsy treatment continues to face significant challenges, including drug resistance and cognitive impairment associated with antiepileptic drugs. 1-Triacontanol cerotate (1TAC), an active component isolated from Marsilea quadrifolia Linn., has emerged as a potential therapeutic avenue for epilepsy. This study investigated the effects of 1TAC on prefrontal cortical neurons and memory retention in chronically epileptic rats, comparing its efficacy to sodium valproate. Our experiment utilized two-month-old adult male Wistar rats, randomly assigned to one of five groups: I - Vehicle Control, II - Rats receiving Pentylenetetrazol (PTZ) at a dosage of 35 mg/kg body weight intraperitoneally every 48 hours, III - Rats given 200 mg/kg body weight of sodium valproate 30 minutes prior to PTZ administration, IV and V - Rats administered 40 and 80 mg/kg body weight of 1-TAC orally 30 minutes before PTZ challenge, respectively. To assess memory performance, we conducted a passive avoidance test. Subsequently, brain specimens were processed for cresyl violet staining to assess cell densities. Results demonstrated that epileptic rats treated with sodium valproate before PTZ administration, and those given 80 mg of 1-Triacontanol cerotate exhibited significantly enhanced memory retention compared to the untreated epileptic group at both 24- and 48-hours post-challenge. Furthermore, 80 mg of 1-Triacontanol cerotate administration showed a protective effect by significantly reducing the loss of pyramidal cells in the medial prefrontal cortex. This intervention effectively minimized the loss of pyramidal neurons in the medial prefrontal cortex and mitigated memory deficits in chronically epileptic rats.

References

  • [1] Singh G, Sander JW. The global burden of epilepsy report: Implications for low- and middle-income countries. Epilepsy Behav. 2020; 105: 106949. https://doi.org/10.1016/j.yebeh.2020.106949.
  • [2] GBD 2016 Epilepsy Collaborators. Global, regional, and national burden of epilepsy, 1990–2016: A systematic analysis for the global burden of disease study 2016. Lancet Neurol. 2019; 18(4): 357–375. https://doi.org/10.1016/S1474-4422(18)30454-X.
  • [3] Cho CH. New mechanism for glutamate hypothesis in epilepsy. Front Cell Neurosci. 2013; 7: 127. https://doi.org/10.3389/fncel.2013.00127.
  • [4] Gelfuso EA, Reis SL, Pereira AMS, Aguiar DSR, Beleboni RO. Neuroprotective effects and improvement of learning and memory elicited by erythravine and 11α-hydroxy-erythravine against the pilocarpine model of epilepsy. Life Sci. 2020; 240: 117072. https://doi.org/10.1016/j.lfs.2019.117072.
  • [5] DiNuzzo M, Mangia S, Maraviglia B, Giove F. Physiological bases of the K+ and the Glutamate/GABA hypotheses of epilepsy. Epilepsy Res. 2014; 108(6): 995–1012. https://doi.org/10.1016/j.eplepsyres.2014.04.001.
  • [6] Landi S, Petrucco L, Sicca F, Ratto GM. Transient cognitive impairment in epilepsy. Front Mol Neurosci. 2018; 11: 458. https://doi.org/10.3389/fnmol.2018.00458.
  • [7] Colciaghi F, Finardi A, Nobili P, Locatelli D, Spigolon G, Battaglia GS. Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia. PLoS One. 2014; 9(2): e89898. https://doi.org/10.1371/journal.pone.0089898.
  • [8] Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, Hong JS, Yoneda Y, Kim HC. Role of oxidative stress in epileptic seizures. Neurochem Int. 2011; 59(2): 122–137. https://doi.org/10.1016/j.neuint.2011.03.025.
  • [9] Wu Q, Zhao CW, Long Z, Xiao B, Feng L. Anatomy based networks and topology alteration in seizure-related cognitive outcomes. Front Neuroanat. 2018; 12: 25. https://doi.org/10.3389/fnana.2018.00025.
  • [10] Rogawski MA, Löscher W, Rho JM. Mechanisms of action of antiseizure drugs and the ketogenic diet. Cold Spring Harb Perspect Med. 2016; 6(5): a022780. https://doi.org/10.1101/cshperspect.a022780.
  • [11] Bromfield EB, Cavazos JE, Sirven JI, editors. An Introduction to Epilepsy [Internet]. West Hartford (CT): American Epilepsy Society; 2006. Available from: https://www.ncbi.nlm.nih.gov/books/NBK2508/
  • [12] Eddy CM, Rickards HE, Cavanna AE. The cognitive impact of antiepileptic drugs. Ther Adv Neurol Disord. 2011; 4(6): 385–407. https://doi.org/10.1177/1756285611417920.
  • [13] Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs. Lancet Neurol. 2012; 11(9): 792–802. https://doi.org/10.1016/S1474-4422(12)70153-9.
  • [14] Park SP, Kwon SH. Cognitive effects of antiepileptic drugs. J Clin Neurol. 2008; 4(3): 99–106. https://doi.org/10.3988/jcn.2008.4.3.99.
  • [15] Choudhary N, Singh V. Insights about multi-targeting and synergistic neuromodulators in ayurvedic herbs against epilepsy: Integrated computational studies on drug-target and protein-protein interaction networks. Sci Rep. 2019; 9(1):10565. https://doi.org/10.1038/s41598-019-46715-6.
  • [16] Manchishi SM. Recent advances in antiepileptic herbal medicine. Curr Neuropharmacol. 2018; 16(1): 79-83. https://doi.org/10.2174/1570159X15666170518151809.
  • [17] Levira F, Thurman DJ, Sander JW, Hauser WA, Hesdorffer DC, Masanja H, Odermatt P, Logroscino G, Newton CR. Premature mortality of epilepsy in low- and middle-income countries: a systematic review from the mortality task force of the international league against epilepsy. Epilepsia. 2017; 58(1): 6–16. https://doi.org/10.1111/epi.13603.
  • [18] Snehunsu A, Mukunda N, Satish Kumar MC, Sadhana N, Naduvil Narayanan S, Vijay Kapgal K, Avinash H, Chandrashekar BR, Raghavendra Rao K, Nayak BS. Evaluation of anti-epileptic property of Marsilea quadrifolia Linn. in maximal electroshock and pentylenetetrazole-induced rat models of epilepsy. Brain Inj. 2013; 27(13–14): 1707–1714. https://doi.org/10.3109/02699052.2013.831121.
  • [19] Snehunsu A, Ghosal C, Kandwal M, Yadav PK, Nayak BS, Rao KR, Kamath SU, Sahoo P, Srinivasan KK, Naduvil Narayanan S, Kumar S, Joseph A. 1-Triacontanol cerotate, isolated from Marsilea quadrifolia Linn. ameliorates reactive oxidative damage in the frontal cortex and hippocampus of chronic epileptic rats. J Ethnopharmacol. 2015; 172: 80–84. https://doi.org/10.1016/j.jep.2015.06.020.
  • [20] Seghatoleslam M, Alipour F, Shafieian R, Hassanzadeh Z, Edalatmanesh MA, Sadeghnia HR, Hosseini M. The Effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats. J Tradit Complement Med. 2016; 6(3): 262–268. https://doi.org/10.1016/j.jtcme.2015.06.003.
  • [21] Pahuja M, Mehla J, Kumar Gupta Y. Anticonvulsant and antioxidative activity of hydroalcoholic extract of tuber of Orchis mascula in pentylenetetrazole and maximal electroshock induced seizures in rats. J Ethnopharmacol. 2012; 142(1): 23–27. https://doi.org/10.1016/j.jep.2012.04.006.
  • [22] Mortazavi F, Ericson M, Story D, Hulce VD, Dunbar GL. Spatial learning deficits and emotional impairments in pentylenetetrazole-kindled rats. Epilepsy Behav. 2005; 7(4): 629–638. https://doi.org/10.1016/j.yebeh.2005.08.019.
  • [23] Snehunsu A, Nayak SB, Kandwal M, Piyali A, Adiga M, Sahoo P, Medabala T, Rao KR, Joseph A. 1-Triacontanol cerotate isolated from Marsilea quadrifolia Linn. safeguards hippocampal CA3 neurons and augments special memory deficit in chronic epileptic rats. Int J Morphol. 2019; 37(1): 265–272. https://doi.org/10.4067/S0717-95022019000100265.
  • [24] Sahu S, Dutta G, Mandal N, Goswami AR, Ghosh T. Anticonvulsant effect of Marsilea quadrifolia Linn. on pentylenetetrazole induced seizure: A behavioral and EEG study in rats. J Ethnopharmacol. 2012; 141(1): 537–541. https://doi.org/10.1016/j.jep.2012.02.039.
  • [25] Zahan R, Ripa F A, Alam M B, Haque M A, Mosaddik M A, Nahar L. Hypoglycemic and in vitro antioxidant effects of methanolic extract of Marsilea quadrifolia plant. Pharmacogn J. 2011; 3(26): 86–92. https://doi.org/10.5530/pj.2011.26.14.
  • [26] Hasselmo, ME. The role of acetylcholine in learning and memory. Curr Opin Neurobiol. 2006; 16(6): 710–715. https://doi.org/10.1016/j.conb.2006.09.002.
  • [27] Bhadra S, Mukherjee PK, Bandyopadhyay A. Cholinesterase inhibition activity of Marsilea quadrifolia Linn. an edible leafy vegetable from west Bengal, India. Nat Prod Res. 2012; 26(16): 1519–1522. https://doi.org/10.1080/14786419.2011.565006.
  • [28] Subramanian A, Tamilanban T, Sekar M, Begum MY, Atiya A, Ramachawolran G, Wong LS, Subramaniyan V, Gan SH, Mat Rani NNI, Wu YS, Chinni SV, Fuloria S, Fuloria NK. Neuroprotective potential of Marsilea quadrifolia Linn against monosodium glutamate-induced excitotoxicity in rats. Front Pharmacol. 2023; 14: 1212376. https://doi.org/10.3389/fphar.2023.1212376
  • [29] Chen CC, Shen JW, Chung NC, Min MY, Cheng SJ, Liu IY. Retrieval of context-associated memory is dependent on the Ca(v)3.2 T-type calcium channel. PLoS One. 2012; 7(1): e29384. https://doi.org/10.1371/journal.pone.0029384.
  • [30] Hess A, Kreitz S, Brune K. Functional atlas of the rat brain. In: Meinzer HP, Handels H, Horsch A, Tolxdorff T. (eds) Bildverarbeitung für die Medizin 2005. Informatik aktuell. Springer, Berlin, 2005, pp.73-77.
  • [31] Govindaiah S, Rao BS, Raju TR, Meti BL. Loss of hippocampal CA1 neurons and learning impairment in subicular lesioned rats. Brain Res. 1997; 745(1-2): 121–126. https://doi.org/10.1016/S0006-8993(96)01135-3.
  • [32] Wood ER, Mumby DG, Pinel JPJ, Phillips AG. Impaired object recognition memory in rats following ischemia-induced damage to the hippocampus. Behav Neurosci. 1993; 107(1): 51-62. https://doi.org/10.1037/0735-7044.107.1.51.
There are 32 citations in total.

Details

Primary Language English
Subjects Medical Pharmacology
Journal Section Articles
Authors

Snehunsu Adhikari 0000-0003-3244-0505

Sayam Subhash 0009-0009-8639-7670

Satheesha Nayak 0000-0003-1421-8222

Christofer Thomas 0000-0002-8899-0496

Chinmay Suryavanshi 0000-0001-9365-2996

Publication Date June 28, 2025
Submission Date November 9, 2023
Acceptance Date January 29, 2024
Published in Issue Year 2024 Volume: 28 Issue: 5

Cite

APA Adhikari, S., Subhash, S., Nayak, S., Thomas, C., et al. (2025). Protection of prefrontal cortex neurons and improvement of memory in epileptic rats by 1-triacontanol cerotate. Journal of Research in Pharmacy, 28(5), 1572-1580.
AMA Adhikari S, Subhash S, Nayak S, Thomas C, Suryavanshi C. Protection of prefrontal cortex neurons and improvement of memory in epileptic rats by 1-triacontanol cerotate. J. Res. Pharm. July 2025;28(5):1572-1580.
Chicago Adhikari, Snehunsu, Sayam Subhash, Satheesha Nayak, Christofer Thomas, and Chinmay Suryavanshi. “Protection of Prefrontal Cortex Neurons and Improvement of Memory in Epileptic Rats by 1-Triacontanol Cerotate”. Journal of Research in Pharmacy 28, no. 5 (July 2025): 1572-80.
EndNote Adhikari S, Subhash S, Nayak S, Thomas C, Suryavanshi C (July 1, 2025) Protection of prefrontal cortex neurons and improvement of memory in epileptic rats by 1-triacontanol cerotate. Journal of Research in Pharmacy 28 5 1572–1580.
IEEE S. Adhikari, S. Subhash, S. Nayak, C. Thomas, and C. Suryavanshi, “Protection of prefrontal cortex neurons and improvement of memory in epileptic rats by 1-triacontanol cerotate”, J. Res. Pharm., vol. 28, no. 5, pp. 1572–1580, 2025.
ISNAD Adhikari, Snehunsu et al. “Protection of Prefrontal Cortex Neurons and Improvement of Memory in Epileptic Rats by 1-Triacontanol Cerotate”. Journal of Research in Pharmacy 28/5 (July 2025), 1572-1580.
JAMA Adhikari S, Subhash S, Nayak S, Thomas C, Suryavanshi C. Protection of prefrontal cortex neurons and improvement of memory in epileptic rats by 1-triacontanol cerotate. J. Res. Pharm. 2025;28:1572–1580.
MLA Adhikari, Snehunsu et al. “Protection of Prefrontal Cortex Neurons and Improvement of Memory in Epileptic Rats by 1-Triacontanol Cerotate”. Journal of Research in Pharmacy, vol. 28, no. 5, 2025, pp. 1572-80.
Vancouver Adhikari S, Subhash S, Nayak S, Thomas C, Suryavanshi C. Protection of prefrontal cortex neurons and improvement of memory in epileptic rats by 1-triacontanol cerotate. J. Res. Pharm. 2025;28(5):1572-80.