Protective Roles of N-trans-feruloyltyramine Against Scopolamine-Induced Cholinergic Dysfunction on Cortex and Hippocampus of Rat Brains

Main Article Content

Wipawan Thangnipon
Sukonthar Ngampramuan
Nopparat Suthprasertporn
Chanati Jantrachotechatchawan
Patoomratana Tuchinda
Saksit Nobsathian


Objective: To study the protective effects of N-trans-feruloyltyramine (NTF) on scopolamine-induced cholinergic dysfunction, apoptosis, and inflammation in rat brains.
Materials and Methods:
Treatments were administered intraperitoneally (i.p.). Wistar rats (8-week-old) were allocated into 4 groups (n = 3) as follows: scopolamine-only, NTF-only, NTF + scopolamine and control. Spatial cognition was evaluated by Morris water maze. ROS assay and Western blot analyses were conducted in 3 brain regions: the frontal cortex, hippocampus, and temporal cortex.
NTF treatment inhibited scopolamine-induced memory impairment and significantly attenuated scopolamine-induced changes in the three brain regions. Investigated scopolamine-associated changes were as follows: increases in ROS production and BACE1 level, decrease in ChAT level, increases in inflammatory and apoptotic markers, and activation of signaling pathway kinases related to inflammation and apoptosis.
With its in vivo antioxidant, cholinergic-promoting, anti-apoptosis, and anti-inflammatory biological activities, NTF is a promising candidate to be further investigated as a potential treatment for Alzheimer’s-associated neurodegeneration.


Download data is not yet available.

Article Details

How to Cite
Thangnipon, W. ., Ngampramuan, S. ., Suthprasertporn, N. ., Jantrachotechatchawan, C. ., Tuchinda, P. ., & Nobsathian, . S. . (2021). Protective Roles of N-trans-feruloyltyramine Against Scopolamine-Induced Cholinergic Dysfunction on Cortex and Hippocampus of Rat Brains. Siriraj Medical Journal, 73(6), 413–422.
Original Article


1 Gold CA, Budson AE. Memory loss in Alzheimer's disease: implications for development of therapeutics. Expert Rev Neurother 2008;8:1879-91.
2 Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 2010;362:329-44.
3 Schliebs R. Basal forebrain cholinergic dysfunction in Alzheimer's disease--interrelationship with β-amyloid, inflammation and neurotrophin signaling. Neurochem Res 2005;30:895-908.
4 Bajo R, Pusil S, López ME, Canuet L, Pereda E, Osipova D, et al. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer's disease. Sci Rep 2015;5:9748.
5 Kim MS, Lee DY, Lee J, Kim HW, Sung SH, Han JS, Jeon WK. Terminalia chebula extract prevents scopolamine-induced amnesia via cholinergic modulation and anti-oxidative effects in mice. BMC Complement Altern Med 2018;18:136.
6 Tuchinda P, Pohmakotr M, Munyoo B, Reutrakul V, Santisuk T. An azaanthracene alkaloid from Polyalthia suberosa. Phytochemistry 2000;53:1079-82.
7 Thangnipon W, Suwanna N, Kitiyanant N, Soi-Ampornkul R, Tuchinda P, Munyoo B, et al. Protective role of N-trans-feruloyltyramine against β-amyloid peptide-induced neurotoxicity in rat cultured cortical neurons. Neurosci Lett 2012;513:229-32.
8 Thangnipon W, Puangmalai N, Chinchalongporn V, Jantrachotechatchawan C, Kitiyanant N, Soi-Ampornkul R, et al. N-benzylcinnamide protects rat cultured cortical neurons from β-amyloid peptide-induced neurotoxicity. Neurosci Lett 2013;556:20-25.
9 Thangnipon W, Suwanna N, Jantrachotechatchawan C, Ngampramuan S, Tuchinda P, Nobsathian S. Protective roles of N-benzylcinnamide on cortex and hippocampus of aged rat brains. Arch Pharm Res 2015;38:1380-8.
10 Chen W, Guo J, Guo H, Kong X, Bai J, Long P. Protective Effect of Vitamin C against Infancy Rat Corneal Injury Caused by Acute UVB Irradiation. Biomed Res Int 2020;2020: 8089273.
11 Noviana R, Ilmiawan MI, Handini M. Synergistic Protective Effect of Commercial Nigella Sativa Oil and Honey Combination against Cisplatin-induced Nephrotoxicity in Rats. Jurnal Biotek Medisiana Indonesia 2020;9:57-66.
12 Franzmeier N, Duering M, Weiner M, Dichgans M, Ewers M, Alzheimer’s Disease Neuroimaging Initiative (ADNI). Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer’s disease. Neurology 2017;88:1054-61.
13 Ballinger EC, Ananth M, Talmage DA, Role LW. Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron 2016;91:1199-218.
14 Alafuzoff I, Arzberger T, Al-Sarraj S, Bodi I, Bogdanovic N, Braak H, et al. Staging of neurofibrillary pathology in Alzheimer’s disease: a study of the Brain Net Europe Consortium. Brain Pathol 2008;18:484-96.
15 Pluta R, Kocki J, Ulamek-Koziol M, Petniak A, Gil-Kulik P, Januszewski S, et al. Discrepancy in expression of β-secretase and amyloid-β protein precursor in Alzheimer-related genes in the rat medial temporal lobe cortex following transient global brain ischemia. J Alzheimer Dis 2016;51:1023-31.
16 DeKosky ST, Ikonomovic MD, Styren SD, Beckett L, Wisniewski S, Bennett DA, et al. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol 2002;51:145-55.
17 Hirokawa S, Nose M, Ishige A, Amagaya S, Oyama T, Ogihara Y. Effect of Hachimi-jio-gan on scopolamine-induced memory impairment and on acetylcholine content in rat brain. J Ethnopharmacol 1996;50:77-84.
18 Piercey MF, Vogelsang GD, Franklin SR, Tang AH. Reversal of scopolamine-induced amnesia and alterations in energy metabolism by the nootropic piracetam: implications regarding identification of brain structures involved in consolidation of memory traces. Brain Res 1987;424:1-9.
19 Jang JY, Kim J, Shim J, Kim CY, Jang JH, Lee KW, Lee JH. Decaffeinated coffee prevents scopolamine-induced memory impairment in rats. Behav Brain Res 2013;245:113-9.
20 Rahimzadegan M, Soodi M. Comparison of Memory Impairment and Oxidative Stress Following Single or Repeated Doses Administration of Scopolamine in Rat Hippocampus. Basic and Clinical Neuroscience 2018;9:4-14.
21 Ali-Melkkila T, Kanto J, Iisalo E. Pharmacokinetics and related pharmacodynamics of anticholinergic drugs. Acta Anaesthesiol Scand 1993;37:633-42.
22 Ebert U, Oertel R, Wesnes KA, Kirch, W. Effects of physostigmine on scopolamine induced changes in quantitative electroencephalogram and cognitive performance. Hum Psychopharmacol 1998;13:199-210.
23 Semphuet T, Boongird A, Tantisira MH, Tiloksakulchai K, Tapechum S, Pakaprot N. The Neuroprotective effect of Bacopa monnieri against Pilocarpine-induced Status epilepticus in rats. Siriraj Med J 2017;69:345-50.
24 Sattayasai J, Chaonapan P, Arkaravichie T, Soi-Ampornkul R, Junnu S, Charoensilp P, et al. Protective effects of mangosteen extract on H2O2-induced cytotoxicity in SK-N-SH cells and scopolamine-induced memory impairment in mice. PLoS One 2013;8(12):e85053.
25 Katagiri T, Hatano N, Aihara M, Kawano H, Okamoto M, Liu Y, et al. Proteomic analysis of proteins expressing in regions of rat brain by a combination of SDS-PAGE with nano-liquid chromatography-quadrupole-time of flight tandem mass spectrometry. Proteome Sci 2010;8:41.
26 Xu QQ, Xu YJ, Yang C, Tang Y, Li L, Cai HB, et al. Sodium Tanshinone IIA sulfonate attenuates scopolamine-induced cognitive dysfunctions via improving cholinergic system. Biomed Res Int 2016;2016:9852536.
27 Ancelin ML, Christen Y, Ritchie K. Is antioxidant therapy a viable alternative for mild cognitive impairment? Examination of the evidence. Dement Geriatr Cogn Disord 2007;24:1-19.
28 Ghosh AK, Osswald HL. BACE1 (β-secretase) inhibitors for the treatment of Alzheimer's disease. Chem Soc Rev 2014;43:6765-813.
29 Hafez HS, Ghareeb DA, Saleh SR, Abady MM, El Demellawy MA, Hussien H, Abdel-Monem N. Neuroprotective effect of ipriflavone against scopolamine-induced memory impairment in rats. Psychopharmacology (Berl) 2017;234:3037-53.
30 Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017;2:17023.
31 Xu T, Shen X, Yu H, Sun L, Lin W, Zhang C. Water-soluble ginseng oligosaccharides protect against scopolamine-induced cognitive impairment by functioning as an antineuroinflammatory agent. J Ginseng Res 2016;40:211-9.
32 Ahmad A, Ramasamy K, Jaafar SM, Majeed AB, Mani V. Total isoflavones from soybean and tempeh reversed scopolamine-induced amnesia, improved cholinergic activities and reduced neuroinflammation in brain. Food Chem Toxicol 2014;65:120-8.
33 Guan QH, Pei DS, Zhang QG, Hao ZB, Xu TL, Zhang GY. The neuroprotective action of SP600125, a new inhibitor of JNK, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampal CA1 via nuclear and non-nuclear pathways. Brain Res 2005;1035:51-59.
34 Hildesheim J, Awwad RT, Fornace AJ Jr. p38 Mitogen-activated protein kinase inhibitor protects the epidermis against the acute damaging effects of ultraviolet irradiation by blocking apoptosis and inflammatory responses. J Invest Dermatol 2004;122:497-502.
35 Tamagno E, Guglielmotto M, Giliberto L, Vitali A, Borghi R, Autelli R, et al. JNK and ERK1/2 pathways have a dual opposite effect on the expression of BACE1. Neurobiol Aging 2009;30:1563-73.
36 Park SJ, Ahn YJ, Oh SR, Lee Y, Kwon G, Woo H, et al. Amyrin attenuates scopolamine-induced cognitive impairment in mice. Biol Pharm Bull 2014;37:1207-13.