ABSTRACT:
Objective: The present investigation aimed to assess the neuroprotective and nootropic potential of trimyristin and dihydroberberine in a scopolamine-induced model of cognitive impairment in Wistar rats. Methods: Scopolamine-induced amnesia in Wistar rats was employed as the experimental model to evaluate cognitive impairment. Cognitive dysfunction was induced by administering scopolamine (1 mg/kg, i.p.). Behavioral performance was assessed using the Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests to evaluate learning and memory functions. The treatment groups received trimyristin (10, 30, and 100 mg/kg, i.p.) and dihydroberberine (25, 50, and 100 mg/kg, p.o.), while donepezil (1 mg/kg, p.o.) was used as the standard reference drug. Biochemical investigations included the estimation of antioxidant parameters, acetylcholinesterase (AChE) activity, brain-derived neurotrophic factor (BDNF), and amyloid-beta levels. Furthermore, histopathological examination of brain tissues was conducted to assess neuronal integrity and neuroprotective effects. Results: Biochemical estimations revealed significant modulation of acetylcholinesterase activity, oxidative stress markers, antioxidant enzymes, brain-derived neurotrophic factor, and amyloid beta levels following treatment. Histopathological observations demonstrated improved neuronal integrity in treated groups. Molecular docking studies further supported cholinergic interaction with acetylcholinesterase receptors. Conclusion: The results demonstrate that trimyristin and dihydroberberine possess notable neuroprotective potential, which may be attributed to their cholinergic modulatory and antioxidant properties.
Cite this article:
Vrushali D.Kakad, Ghanshyam B. Jadhav. Neuroprotective Effects of Trimyristin and Dihydroberberine Against Scopolamine-Induced Cognitive Impairment in Rats. Research Journal of Pharmacy and Technology. 2026;19(8):3895-4. doi: 10.52711/0974-360X.2026.00548
Cite(Electronic):
Vrushali D.Kakad, Ghanshyam B. Jadhav. Neuroprotective Effects of Trimyristin and Dihydroberberine Against Scopolamine-Induced Cognitive Impairment in Rats. Research Journal of Pharmacy and Technology. 2026;19(8):3895-4. doi: 10.52711/0974-360X.2026.00548 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2026-19-8-65
REFERENCES:
1. Das SK, Chakraborthy GS, Chakrabarti T, Chakrabarti P, Gholamzadeh MJ, Nami M. Evaluation of nootropic activity of standardized Epipremnum aureum extract against scopolamine-induced amnesia in experimental animals. Journal of Advanced Medical Sciences and Applied Technologies. 2021 Jan 1; 6(1):64-71.
2. Hussain H, Ahmad S, Shah SWA, Ullah A, Ali N, Almehmadi M, Ahmad M, Khalil AAK, Jamal SB, Ahmad H, et al. Attenuation of scopolamine-induced amnesia via cholinergic modulation in mice by synthetic curcumin analogs. Molecules. 2022 Apr 14; 27(8):2468. Doi: 10.3390/molecules27082468.
3. Mahadik VJ, Chavare MN, Patil SS, Wadkar KA. Cognition enhancing potential of Sesbania grandiflora fruit extract in scopolamine induced amnesia in mice. Research Journal of Pharmacy and Technology. 2020 Nov 1; 13(11):5057-5062. doi: 10.5958/0974-360X.2020.00886.0.
4. Blokland A. Acetylcholine: A neurotransmitter for learning and memory? Brain Research Reviews. 1995 Dec 1; 21(3):285-300. doi: 10.1016/0165-0173(95)00016-X.
5. Kiran R, Rao GS, Krishna NS, Jahnavi NB, Begum SA, Anusha E. Memory enhancing activity of Ageratum conyzoides L. on corticosterone-induced dementia in mice. International Journal of Pharmacological Screening Methods. 2012; 2(2):77-81.
6. Krishna V, Nayak V, Pandey AK, Sunny SV, Bairy KL. Chronic treatment with escitalopram reversed scopolamine-induced memory impairment by enhancing cholinergic activity in Wistar albino rats. Research Journal of Pharmacy and Technology. 2021 Apr 1; 14(4):1887-1892. doi: 10.52711/0974-360X.2021.00333.
7. Nigam A, Kulshreshtha M, Panjwani D. Pharmacological evaluation of Hibiscus abelmoschus against scopolamine-induced amnesia and cognitive impairment in mice. Advanced Human Biology. 2019 May 1; 9(2):116-123. doi: 10.4103/AIHB.AIHB_18_19.
8. Jadhav G B, Sabale R R. Gramine and zingerone mitigates neuroinflammation related depressive behaviour induced by chronic unpredictable mild stress in rat . Research J. Pharm. and Tech. 2023 July 16 (7):3067-3074.
9. Narwanto MI, Rahayu M, Soeharto S, Nurdiana, Widodo MA. Neuroprotective potency of Tamarindus indica seed extract for preventing memory impairment in rat model of Alzheimer's disease. Research Journal of Pharmacy and Technology. 2020 Sep 1; 13(9):4041-4046. doi: 10.5958/0974-360X.2020.00714.3.
10. Xu L, Lin G, Yu Q, Li Q, Mai L, Cheng J, Xie J, Liu Y, Su Z, Li Y. Anti-hyperuricemic and nephroprotective effects of dihydroberberine in potassium oxonate- and hypoxanthine-induced hyperuricemic mice. Frontiers in Pharmacology. 2021 Mar 30; 12:645879. doi: 10.3389/fphar.2021.645879.
11. Li C, Dong N, Wu B, Mo Z, Xie J, Lu Q. Dihydroberberine, an isoquinoline alkaloid, exhibits protective effect against dextran sulfate sodium-induced ulcerative colitis in mice. Phytomedicine. 2021 Sep 1; 90:153631. doi: 10.1016/j.phymed.2021.153631.
12. Adelaja A, Ameen M, Quadri T, Odubela K, Omotoso G, Yahya R, Biliaminu S, Adeyanju M, Ebito G, Otulana J. Extraction, isolation and evaluation of anti-toxic principles from Moringa oleifera (MOF6) and Myristica fragrans (trimyristin) upregulated acetylcholinesterase concentrations in sodium arsenite-induced neurotoxicity in rats. Journal of Phytomedicine and Therapeutics. 2020 Jul 1; 19(2):467-476.
13. Peitzika SC, Pontiki E. A review on recent approaches on molecular docking studies of novel compounds targeting acetylcholinesterase in Alzheimer disease. Molecules. 2023 Jan 26; 28(3):1084. doi: 10.3390/molecules28031084.
14. Farihi A, Bouhrim M, Chigr F, Elbouzidi A, Bencheikh N, Zrouri H, Nasr FA, Parvez MK, Alahdab A, Ahami AOT. Exploring medicinal herbs’ therapeutic potential and molecular docking analysis for compounds as potential inhibitors of human acetylcholinesterase in Alzheimer’s disease treatment. Medicina (Kaunas). 2023 Oct 13; 59(10):1812. doi: 10.3390/medicina59101812.
15. Hakeem IJ. Molecular docking analysis of acetylcholinesterase inhibitors for Alzheimer's disease management. Bioinformation. 2023 May 31; 19(5):565-570. doi: 10.6026/97320630019565.
16. Jadhav G B., Sabale R R et al., Exploring Acute and Sub-Acute Toxicity of Gramine Bioactive Molecule in Wistar Rats BIOSCIENCES BIOTECHNOLOGY RESEARCH ASIA, December 2023. Vol. 20(4), p. 1341-1354.
17. Aglawe MM, Kale MB, Rahangdale SR, Kotagale NR, Umekar MJ, Taksande BG. Agmatine improves the behavioral and cognitive impairments associated with chronic gestational ethanol exposure in rats. Brain Research Bulletin. 2021 Jan 1; 167:37-47. doi: 10.1016/j.brainresbull.2020.11.015.
18. Tillmann S, Wegener G. Probiotics reduce risk-taking behavior in the elevated plus maze in the Flinders Sensitive Line rat model of depression. Behavioural Brain Research. 2019 Feb 18; 359:755-762. doi: 10.1016/j.bbr.2018.08.025.
19. Jadhav G B.,Bhure R R. et al., Effect of Cuscuta reflexa extract on Experimentally Induced Hypertension in normal and Streptozotocin Induced Diabetes in Rats.Research J. Pharm. and Tech. 2020 March 13(3):1351-1355. doi: 10.5958/0974-360X.2020.00249.8
20. Gage GJ, Kipke DR, Shain W. Whole animal perfusion fixation for rodents. Journal of Visualized Experiments. 2012 Jul 30; (65):e3564. doi: 10.3791/3564.
21. Ghumatkar PJ, Patil SP, Jain PD, Tambe RM, Sathaye S. Nootropic, neuroprotective and neurotrophic effects of phloretin in scopolamine-induced amnesia in mice. Pharmacology Biochemistry and Behavior. 2015 Aug 1; 135:182-191. doi: 10.1016/j.pbb.2015.06.005.
22. Sampada S. Bhosale, S. Sivakkumar, Shrirang Jamadagni, Arulmozhi S. Therapeutic potential of Bhiramiyadhi bhavanai choornam in ameliorating scopolamine-induced impaired learning and memory in rats: neuroprotective effects and mechanistic insights. Research Journal of Pharmacy and Technology. 2024; 17(2):553-2. doi: 10.52711/0974-360X.2024.00086
23. Shah K, Kumar RG, Verma S, Dubey RS. Effect of cadmium on lipid peroxidation, superoxide anion generation and activities of antioxidant enzymes in growing rice seedlings. Plant Science. 2001 Dec 1; 161(6):1135-1144. doi: 10.1016/S0168-9452(01)00517-9
24. Ellman GL, Courtney KD, Andres V Jr, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology. 1961 Jul 1; 7:88-95. doi: 10.1016/0006-2952(61)90145-9.
25. 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. Neurological Research. 2018 Apr 1; 40(4):324-333. doi: 10.1080/01616412.2018.1441776.
26. Garcia-Osta A, Alberini CM. Amyloid beta mediates memory formation. Learning and Memory. 2009 Apr 1;16(4):267-272. doi: 10.1101/lm.1310209.
27. Chithrapady S, Vittalrao AM, Kamalkishore MK, Shenoy VB, Gadahad MRK. Cognition enhancing ability of vitamin D, ipriflavone and their combination against scopolamine induced amnesia in REM sleep deprived rats. Research Journal of Pharmacy and Technology. 2026 Apr 1; 19(4):1511-1519. doi: 10.52711/0974-360X.2026.00217.
28. Rajangam J, Parthasaradhi DP, Kotakonda M, Palei NN, Muthumanickam A, Subramanam NK, Bindhu H. Neurocognitive and neuroprotective potential of Mimusops elengi in mice model of scopolamine-induced amnesia. Drug Discovery. 2023; 17:e7dd1008. doi: 10.54905/disssi.v17i39.e7dd1008.
29. Gnanaraj C, Sekar M, Fuloria S, Swain SS, Gan SH, Chidambaram K, Rani NNIM, Balan T, Stephenie S, Lum PT, et al. In silico molecular docking analysis of karanjin against Alzheimer’s and Parkinson’s diseases as a potential natural lead molecule for new drug design, development and therapy. Molecules. 2022 May 3; 27(9):2834. doi: 10.3390/molecules27092834.
30. Haritha PH, Lakshmi Narayanan T, Babu A, Ariharasivakumar G, Thekkekkara D. Evaluation of anti-amnesic activity of Ayurvedic formulation Saraswathaghrita in the scopolamine-induced rat model. Research Journal of Pharmacy and Technology. 2023 Aug 1; 16(8):3658-3664. doi: 10.52711/0974-360X.2023.00602.
31. Ghalibaf MHE, Rajabian A, Parviz M, Akbarian M, Amirahmadi S, Vafaee F, Hosseini M. Minocycline alleviated scopolamine-induced amnesia by regulating antioxidant and cholinergic function. Heliyon. 2023 Feb 1; 9(2):e13452. doi: 10.1016/j.heliyon.2023.e13452.
32. Jaberi S, Fahnestock M. Mechanisms of the beneficial effects of exercise on brain-derived neurotrophic factor expression in Alzheimer's disease. Biomolecules. 2023 Oct 26; 13(11):1577. doi: 10.3390/biom13111577.