Role of lychee seed extract in alleviation of ethanol-induced oxidative brain damage and memory deficit via its antioxidant and acetylcholinesterase inhibitory activities in rats

Wathita Phachonpai Chatawal Tongun Prathakphong Riyamongkol Dej Mann Teera Chanmanee Watcharaporn Predapirom Jeefoo   

Open Access   

Published:  May 13, 2025

DOI: 10.7324/JAPS.2025.219863
Abstract

Chronic alcohol consumption is a serious problem that can destroy brain structure and function and lead to cognitive decline. Brain-boosting supplements have gained popularity as a strategy to improve memory impairment, as well as cholinergic and oxidative stress. We aimed to evaluate the potency of lychee seed extract to combat the memory deficit in a rat model of alcoholism. Male rats were given 25% ethanol and administered orally with lychee seed extract (300 and 600 mg/kg/day) or donepezil (3 mg/kg/day) for 42 days. The object recognition and Morris water maze procedures were used to investigate memory performance. Brain oxidative markers, lipid peroxidation, and acetylcholinesterase (AChE) activity in both cortex and hippocampus of ethanol-treated rats were also determined. The continuous drinking of alcohol led to an induction in oxidative stress, and lipid peroxidation, and increased AChE activity resulted in a greater cognitive impairment. However, both doses of lychee seed extract were able to reduce AChE activity and increase brain antioxidant status, along with decreasing lipid peroxidation in both areas of the rat brain. Overall, lychee seed extract supplementation, a waste product from the direct consumption and fruit processing industry, reverses alcohol-induced memory decline via its antioxidative neuroprotection and inhibition of AChE activity.


Keyword:     Lychee seed alcoholism antioxidants cognition acetylcholinesterase


Citation:

Phachonpai W, Tongun C, Riyamongkol P, Mann D, Chanmanee T, Jeefoo WP. Role of lychee seed extract in alleviation of ethanol-induced oxidative brain damage and memory deficit via its antioxidant and acetylcholinesterase inhibitory activities in rats. J Appl Pharm Sci. 2025. Online First.http://doi.org/10.7324/JAPS.2025.219863

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

1. Sudhinaraset M, Wigglesworth C, Takeuchi DT. Social and cultural contexts of alcohol use: influences in a social-ecological framework. Alcohol Res. 2016;38(1):35-45.

2. Ma J, Xiong F, Li Z, Dong G, Sun X, Yin W, et al. The effect of chronic alcohol exposure on spatial memory and BDNF-TrkB- PLCγ1 signaling in the hippocampus of male and female mice. Heliyon. 2023;9(6):e16660. https://doi.org/10.1016/j.heliyon.2023.e16660

3. Macht VA, Vetreno RP, Crews FT. Cholinergic and neuroimmune signaling interact to impact adult hippocampal neurogenesis and alcohol pathology across development. Front Pharmacol. 2022;13:849997. https://doi.org/10.3389/fphar.2022.849997

4. Crews FT, Fisher R, Deason C, Vetreno RP. Loss of basal forebrain cholinergic neurons following adolescent binge ethanol exposure: recovery with the cholinesterase inhibitor galantamine. Front Behav Neurosci. 2021;15:652494. https://doi.org/10.3389/fnbeh.2021.652494

5. Mesulam MM, Guillozet A, Shaw P, Levey A, Duysen EG, Lockridge O. Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine. Neuroscience. 2002;110(4):627-39. https://doi.org/10.1016/S0306-4522(01)00613-3

6. Cadete-Leite A, Andrade JP, Sousa N, Ma W, Ribeiro-da-Silva A. Effects of chronic alcohol consumption on the cholinergic innervation of the rat hippocampal formation as revealed by choline acetyltransferase immunocytochemistry. Neuroscience. 1995;64(2):357-74. https://doi.org/10.1016/0306-4522(94)00330-8

7. Moreta MP, Burgos-Alonso N, Torrecilla M, Marco-Contelles J, Bruzos-Cidón C. Efficacy of acetylcholinesterase inhibitors on cognitive function in Alzheimer's disease. Review of reviews. Biomedicines. 2021;9(11):1689. https://doi.org/10.3390/biomedicines9111689

8. Cortez I, Brocardo PS, Leasure JL. Changes in affective behavior and oxidative stress after binge alcohol in male and female rats. Brain Sci. 2021;11(9):1250. https://doi.org/10.3390/brainsci11091250

9. Hernández JA, López-Sánchez RC, Rendón-Ramírez A. Lipids and oxidative stress associated with ethanol-induced neurological damage. Oxid Med Cell Longev. 2016;2016:1543809. https://doi.org/10.1155/2016/1543809

10. Augustyniak A, Michalak K, Skrzydlewska E. The action of oxidative stress induced by ethanol on the central nervous system (CNS). Postepy Hig Med Dosw. 2005;59:464-71.

11. Tsermpini EE, Plemenitaš Ilješ A, Dolžan V. Alcohol-induced oxidative stress and the role of antioxidants in alcohol use disorder: a systematic review. Antioxidants (Basel). 2022;11(7):1374. https://doi.org/10.3390/antiox11071374

12. Pacheco MT, Moreno FJ, Villamiel M. Chemical and physicochemical characterization of orange by-products derived from industry. J Sci Food Agric. 2019;99(2):868. https://doi.org/10.1002/jsfa.9257

13. Abotaleb M, Liskova A, Kubatka P, Büsselberg D. Therapeutic potential of plant phenolic acids in the treatment of cancer. Biomolecules. 2020;10(2):221. https://doi.org/10.3390/biom10020221

14. Kittipongpittaya K, Puangploy P, Kullamethee P, Fakkheow P, Kareevate P, Philkliang B. Antioxidant activities of extract from Makmao seed waste. Asia Pac J Sci Technol. 2021;26(2):26.

15. Floris S, Fais A, Rosa A, Piras A, Marzouki H, Medda R, et al. Phytochemical composition and the cholinesterase and xanthine oxidase inhibitory properties of seed extracts from the Washingtonia filifera palm fruit. RSC Adv. 2019;9:21278-87. https://doi.org/10.1039/C9RA02928A

16. Kobus-Cisowska J, Szymanowska D, Maciejewska P, Kmiecik D, Gramza-Micha?owska, A, Kulczy?ski,B, et al. In vitro screening for acetylcholinesterase and butyrylcholinesterase inhibition and antimicrobial activity of chia seeds (Salvia hispanica). Electron J Biotechnol. 2018;37:1-10. https://doi.org/10.1016/j.ejbt.2018.10.002

17. Saadh MJ. Potential protective effects of red grape seed extract in a rat model of malathion-induced neurotoxicity. Vet World. 2023;16(2):380-5. https://doi.org/10.14202/vetworld.2023.380-385

18. Subhadrabandhu S, Yapwattanaphun C. Lychee and longan production in Thailand. Acta Horticulturae. 2001;558:49-57. https://doi.org/10.17660/ActaHortic.2001.558.5

19. Zhang Y, Jin D, An X, Duan L, Duan Y, Lian F. Lychee seed as a potential hypoglycemic agent, and exploration of its underlying mechanisms. Front Pharmacol. 2021;12:737803. https://doi.org/10.3389/fphar.2021.737803

20. Xiao LY, Pan ZJ, Rao WN. The research of protective effect of Litchi seed of experimental liver injury in mice. Chin J Trad Chin Med Pharm. 2005;20:42-4.

21. Sun W, Shahrajabian MH, Shen H, Cheng Q. Lychee (Litchi chinensis Sonn.), the king of fruits, with both traditional and modern pharmacological health benefits. Phcog Commn. 2021;11:22-5. https://doi.org/10.5530/pc.2021.1.5

22. Deng ZJ, Guo JW, Pan JQ. Pharmacologic and pharmacodynamic effects of effective element of Litchi and Litchi seed. Pharm Today. 2009;5:7-9.

23. Xiao ZJ, Guo JW, Xu F. Effect of litchi saponin and litchi flavones on insulin resistance in HepG2 cells. J Pharm Pract. 2015;4:316-8.

24. Zhang YM, Yuan H, Tian JX, Shen L, Yong YH. Effects of saponin of litchi seed on gluconeogenesis and metabolism of blood lipid in mice. J Hangzhou Teach Coll. 2005;6:435-6.

25. Zhang J, Zhang C. Research progress on the antineoplastic pharmacological effects and mechanisms of litchi seeds. Chin Med. 2015;6:20-6. https://doi.org/10.4236/cm.2015.61003

26. Li W, Zhu YT, Huang ZY, He JJ, Pei J, Song JP. Experimental studies on anti-fluvirus effect of Litchi seed in vivo. Chin J Ethnomed Ethnopharm. 2011;18:34-6.

27. Zhao HX, Guo K, Cui YD, Wu XG, Shang YZ. Effect of Scutellaria barbata flavonoids on abnormal changes of Bcl-2, Bax, Bcl-xL and Bak protein expression in mitochondrial membrane induced by composite Aβ(25-35). Chin J Pathophysiol. 2014;30:2262-6.

28. Ye HM, Zhong CY, Huang MX, Wang CY, Fang X, Chen XY, et al. Effect of litchi seed aqueous extracts on learning and memory obstacles induced by d-galactose in mice and its mechanism. J Chin Med Mater. 2013;36:438-40.

29. Singleton VL, Orthofer R, Lamuela-Raventós RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Methods Enzymol. 1999;299:152-78. https://doi.org/10.1016/S0076-6879(99)99017-1

30. Akowuah GA, Ismail Z, Norhayati I, Sadikun A. The effects of different extraction solvents of varying polarities of polyphenols of Orthosiphon stamineus and evaluation of the free radical scavenging activity. Food Chem. 2005;93(2):311-7. https://doi.org/10.1016/j.foodchem.2004.09.028

31. Benzie IFF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of ''antioxidant power'': the FRAP assay. Anal Biochem. 1996;239(1):70-6. https://doi.org/10.1006/abio.1996.0292

32. Rajakrishnan V, Menon VP. Protective role of curcumin in ethanol toxicity. Phytotherapy Res. 1998;12:55-6. https://doi.org/10.1002/(SICI)1099-1573(19980201)12:1<55::AID-PTR173>3.0.CO;2-0

33. Gotz ME, Janetzky B, Pohli S, Gottschalk A, Gsell W, Tatschner T, et al. Chronic alcohol consumption and cerebral indices of oxidative stress: is there a link? Alcohol Clin Exp Res. 2001;25:717-25. https://doi.org/10.1111/j.1530-0277.2001.tb02272.x

34. Tongun T, Phachonpai W. Cognitive booster of wampee peel extract on chronic restraint stress-induced memory dysfunction in rats. J Appl Pharm Sci. 2020;10(7):19-26. https://doi.org/10.1016/j.heliyon.2021.e07003

35. Jeefoo WP, Phachonpai W, Duangjai A, Ontawong A, Amornlerdpison D. Purple eggplant (Solanum melongena L.) ameliorates D-galactose-induced cognitive impairment through inhibition of oxidative stress and acetylcholinesterase in the hippocampus of an aging rat model. Trends Sci. 2023;21(1):7245. https://doi.org/10.48048/tis.2024.7245

36. Phachonpai W. Tongun T. Neuroprotective and cognitive enhancing effects of Clausena lansium (Lour.) skeels peels extract in ischemic rat brains. J Appl Pharm Sci. 2021;11(9):1-8.

37. Moron MA, Depierre JW, Mannervick B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582:67-78. https://doi.org/10.1016/0304-4165(79)90289-7

38. Pohsa S, Hanchang W, Singpoonga N, Chaiprasart P, Taepavarapruk P. Effects of cultured Cordycep militarison sexual performance and erectile function in streptozotocin-induced diabetic male rats. Biomed Res Int. 2020;2020:4198397. https://doi.org/10.1155/2020/4198397

39. Nakdook W, Khongsombat O, Taepavarapruk P, Taepavarapruk N, Ingkaninan K. The effects of Tabernaemontana divaricata root extract on amyloid β-peptide 25-35 peptides induced cognitive deficits in mice. J Ethnopharmacol. 2010;130:122-6. https://doi.org/10.1016/j.jep.2010.04.027

40. Shoaib S, Ansari MA, Fatease AA, Safhi AY, Hani U, Jahan R, et al. Plant-derived bioactive compounds in the management of neurodegenerative disorders: challenges, future directions and molecular mechanisms involved in neuroprotection. Pharmaceutics. 2023;15(3):749. https://doi.org/10.3390/pharmaceutics15030749

41. Costin BN, Miles MF. Molecular and neurologic responses to chronic alcohol use. Handb Clin Neurol. 2014;125:157-71. https://doi.org/10.1016/B978-0-444-62619-6.00010-0

42. Hartley T, Lever C, Burgess N, O'Keefe J. Space in the brain: how the hippocampal formation supports spatial cognition. Philos Trans R Soc Lond B Biol Sci. 2013;369(1635):20120510. https://doi.org/10.1098/rstb.2012.0510

43. Owen AM, Stern CE, Look RB, Tracey I, Rosen BR, Petrides M. Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex. Proc Natl Acad Sci U S A. 1998;95(13):7721-6. https://doi.org/10.1073/pnas.95.13.7721

44. Pérez-Cervera L, De Santis S, Marcos E, Ghorbanzad-Ghaziany Z, Trouvé-Carpena A, Selim MK, et al. Alcohol-induced damage to the fimbria/fornix reduces hippocampal-prefrontal cortex connection during early abstinence. Acta Neuropathol Commun. 2023;11(1):101. https://doi.org/10.1186/s40478-023-01597-8

45. Cippitelli A, Zook M, Bell L, Damadzic R, Eskay RL, Schwandt M, et al. Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats. Neurobiol Learn Mem. 2010;94(4):538-46. https://doi.org/10.1016/j.nlm.2010.09.006

46. Kamal H, Tan GC, Ibrahim SF, Shaikh MF, Mohamed IN, Mohamed RMP, et al. Alcohol use disorder, neurodegeneration, Alzheimer's and Parkinson's disease: interplay between oxidative stress, neuroimmune response and excitotoxicity. Front Cell Neurosci. 2020;14:282. https://doi.org/10.3389/fncel.2020.00282

47. Rico EP, Rosemberg D, Dias RD, Bogo MR, Bonan CD. Ethanol alters acetylcholinesterase activity and gene expression in zebrafish brain. Toxicol Lett. 2007;174:25-30. https://doi.org/10.1016/j.toxlet.2007.08.005

48. Phachonpai W, Wattanathorn J, Wannanon P, Thipkaew C, Sripanidkulchai B, Muchimapura S. Coscinium Fenestratum protects against ethanol-induced neurodegeneration in adult rat brain. Am J Pharmacol Toxicol. 2012;7(3):81-8. https://doi.org/10.3844/ajptsp.2012.81.88

49. Macieira MS, Almeida WG, Silva EA, Schenberg LC, Nakamura-Palacios EM. Alcohol dependence induced in rats by semi voluntary intermittent intake. Braz J Med Biol Res. 1997;30(9):1107-11. https://doi.org/10.1590/S0100-879X1997000900009

50. Bruijniks SJE, van Grootheest G, Cuijpers P, de Kluiver H, Vinkers CH, Peeters F, et al. Working memory moderates the relation between the brain-derived neurotropic factor (BDNF) and psychotherapy outcome for depression. J Psychiatr Res. 2020;130:424-32. https://doi.org/10.1016/j.jpsychires.2020.07.045

51. Cichon N, Saluk-Bijak J, Gorniak L, Przyslo L, Bijak M. Flavonoids as a natural enhancer of neuroplasticity-an overview of the mechanism of neurorestorative action. Antioxidants. 2020;9:1035. https://doi.org/10.3390/antiox9111035

52. AL-Qahtani AA, Shati AA, Al-Doaiss AA. Elsaid FG. Mitigating alcohol-induced neurohepatotoxicity in male albino rats with avocado and mustard. J Umm Al-Qura Univ. Appll Sci. 2024;10:530-40. https://doi.org/10.1007/s43994-024-00124-2

53. Hossain S, Chowdhury I, Basunia M, Nahar T, Rahaman A, Choudhury B, et al. Syzygium cumini seed extract protects the liver against lipid peroxidation with concurrent amelioration of hepatic enzymes and lipid profile of alcoholic rats. JCIM. 2011;8(1):1-17. https://doi.org/10.2202/1553-3840.1445

54. Bera D, Lahiri D, Nag A. Studies on a natural antioxidant for stabilization of edible oil and comparison with synthetic antioxidants. J Food Eng. 2006;74:542-5. https://doi.org/10.1016/j.jfoodeng.2005.03.042

55. Potisate Y, Pintha K. Optimum extraction condition and dehydration of lychee seeds extracted. Health Sci Tech Rev. 2021;14(2):105-15

56. Omena CMB, Valentim IB, Guedes GS, Rabelo LA, Mano CM, Bechara EJH, et al. Antioxidant, anti-acetylcholinesterase and cytotoxic activities of ethanol extracts of peel, pulp and seeds of exotic Brazilian fruits. Food Res Int. 2012;49:334-44. https://doi.org/10.1016/j.foodres.2012.07.010

57. Findik BT, Yildiz H, Akdeniz M, Yener I, Yilmaz MA, Cakir O, et al. Phytochemical profile, enzyme inhibition, antioxidant, and antibacterial activity of Rosa pimpinellifolia L.: a comprehensive study to investigate the bioactivity of different parts (whole fruit, pulp, and seed part) of the fruit. Food Chem. 2024;15;455:139921. https://doi.org/10.1016/j.foodchem.2024.139921

58. Shin CY, Kim HS, Cha KH, Won DH, Lee JY, Jang SW, et al. The effects of donepezil, an acetylcholinesterase inhibitor, on impaired learning and memory in rodents. Biomol Ther (Seoul). 2018;26(3):274-81. https://doi.org/10.4062/biomolther.2017.189

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