Author(s):
Shravya Chithrapady, Amberkar Mohanbabu Vittalrao, Meena Kumari Kamalkishore, Vijetha Belle Shenoy, Mohandas Rao Kapettu Gadahad
Email(s):
meena.kumari@manipal.edu
DOI:
10.52711/0974-360X.2026.00217 
Address:
Shravya Chithrapady1, Amberkar Mohanbabu Vittalrao2, Meena Kumari Kamalkishore1, Vijetha Belle Shenoy3, Mohandas Rao Kapettu Gadahad4
1Department of Pharmacology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India.
2Department of Pharmacology, The Oxford Medical College, Hospital and Research Centre, Bengaluru, India.
3Department of Biochemistry, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India.
4Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal, India.
*Corresponding Author
Published In:
Volume - 19,
Issue - 4,
Year - 2026
ABSTRACT:
Sleep is crucial for various functions linked to learning and memory. Literature reports that sleep insufficiency affects around 18% of adults globally. Recent research emphasizes the use of natural components over synthetic compounds. No studies have explored to study the effect of natural components like vitamin D and ipriflavone on sleep deprivation-induced cognitive impairment. Our study aims to observe their impact on REM sleep-deprived rats administered with scopolamine. Forty-two albino rats were categorized into seven groups (n=6). Group 1 was REM control (without-SD) and group 2 include REM sleep deprived rats. Group 3 was REM sleep-deprived rats treated with scopolamine and group 4-7 consisting of REM sleep-deprived along with scopolamine was administered vitamin D, ipriflavone, donepezil, and (vitamin D + ipriflavone) combination respectively. By using modified multiple-platform, REM sleep was induced in rats and morris water maze was used to assess spatial learning and memory . Rat hippocampal tissue was subjected to biochemical and histopathological examination to assess anti-amnesic action of the drugs. The result showed groups treated with vitamin D, and ipriflavone combination showed better antioxidant properties as evidenced by reduced glutathione, and decreased prooxidant level, specifically malondialdehyde and nitric oxide, compared to donepezil group. Similarly, there was a significant increase in Brain-Derived-Neurotropic-Factor level and decreased cholesterol level in the treated group. Furthermore, acetylcholinesterase activity in the treated group was comparable to that of the standard donepezil group, in contrast to the sleep-deprived and sleep-deprived + scopolamine groups. Behavioural analysis showed better performance in the treated group which is similar to standard donepezil group. Histopathological analysis showed increased healthy neurons in the treated group compared to that of sleep-deprived and sleep-deprived+ scopolamine. This study indicated that ipriflavone, vitamin D and their combination could enhance cognition, and their effect may be comparable to the standard drug donepezil.
Cite this article:
Shravya Chithrapady, Amberkar Mohanbabu Vittalrao, Meena Kumari Kamalkishore, Vijetha Belle Shenoy, Mohandas Rao Kapettu Gadahad. 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;19(4):1511-9. doi: 10.52711/0974-360X.2026.00217
Cite(Electronic):
Shravya Chithrapady, Amberkar Mohanbabu Vittalrao, Meena Kumari Kamalkishore, Vijetha Belle Shenoy, Mohandas Rao Kapettu Gadahad. 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;19(4):1511-9. doi: 10.52711/0974-360X.2026.00217 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2026-19-4-6
REFERENCES:
1. Bird CM, Burgess N. The hippocampus and memory: insights from spatial processing. Nature Reviews Neuroscience. 2008 Mar; 9(3): 182-94. DOI:10.1038/nrn2335
2. Rasch B, Born J. About sleep's role in memory. Physiological Reviews. 2013 Apr 1. DOI:10.1152/physrev.00032.2012
3. Villafuerte G, Miguel-Puga A, Murillo Rodríguez E, Machado S, Manjarrez E, Arias-Carrión O. Sleep deprivation and oxidative stress in animal models: a systematic review. Oxidative Medicine and Cellular Longevity. 2015; 2015(1): 234952. DOI: 10.1155/2015/234952
4. Medic G, Wille M, Hemels ME. Short-and long-term health consequences of sleep disruption. Nature and science of sleep. 2017 May 19:151-61. DOI: 10.2147/NSS.S134864
5. Altevogt B and Colten HR. Sleep disorders and sleep deprivation: an unmet public health problem. 2006. DOI: 10.17226/11617
6. Diekelmann S, Born J. The memory function of sleep. Nature Reviews Neuroscience. 2010 Feb; 11(2): 114-26. DOI: 10.1038/nrn2762
7. Saksvik-Lehouillier I, Saksvik SB, Dahlberg J, Tanum TK, Ringen H, Karlsen HR, Smedbøl T, Sørengaard TA, Stople M, Kallestad H, Olsen A. Mild to moderate partial sleep deprivation is associated with increased impulsivity and decreased positive affect in young adults. Sleep. 2020 Oct; 43(10): zsaa078. DOI: 10.1093/sleep/zsaa078
8. Uccella S, Cordani R, Salfi F, Gorgoni M, Scarpelli S, Gemignani A, Geoffroy PA, De Gennaro L, Palagini L, Ferrara M, Nobili L. Sleep deprivation and insomnia in adolescence: implications for mental health. Brain Sciences. 2023 Mar 28; 13(4): 569. DOI: 10.3390/brainsci13040569
9. Alhola P, Polo-Kantola P. Sleep deprivation: Impact on cognitive performance. Neuropsychiatric Disease and Treatment. 2007 Oct 1; 3(5): 553-67.
10. Perlis ML, Giles DE, Mendelson WB, Bootzin RR, Wyatt JK. Psychophysiological insomnia: the behavioural model and a neurocognitive perspective. Journal of Sleep Research. 1997 Sep; 6(3): 179-88. DOI: 10.1046/j.1365-2869.1997.00045.x
11. Dzobo K. The role of natural products as sources of therapeutic agents for innovative drug discovery. Comprehensive Pharmacology. 2022: 408. DOI: 10.1016/B978-0-12-820472-6.00041-4
12. Sun W, Sanderson PE, Zheng W. Drug combination therapy increases successful drug repositioning. Drug Discovery today. 2016 Jul 1; 21(7): 1189-95. DOI: 10.1016/j.drudis.2016.05.015
13. O. Beauchet, L. A. Cooper-Brown and G. Allali, “Vitamin D supplementation and cognition in adults: a systematic review of randomized controlled trials”, CNS Drugs, 2021; 35: 1249-64. DOI: 10.1007/s40263-021-00876-z
14. Rimmelzwaan LM, van Schoor NM, Lips P, Berendse HW, Eekhoff EM. Systematic review of the relationship between vitamin D and Parkinson’s disease. Journal of Parkinson's disease. 2016 Jan 1; 6(1): 29-37. DOI: 10.3233/JPD-150615
15. Chai B, Gao F, Wu R, Dong T, Gu C, Lin Q, Zhang Y. Vitamin D deficiency as a risk factor for dementia and Alzheimer’s disease: An updated meta-analysis. BMC Neurology. 2019 Dec; 19: 1-1. DOI: 10.1186/s12883-019-1500-6
16. Gorzkiewicz J, Bartosz G, Sadowska-Bartosz I. The potential effects of phytoestrogens: The role in neuroprotection. Molecules. 2021 May 16; 26(10): 2954. DOI: 10.3390/molecules26102954
17. 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. 2017 Oct; 234: 3037-53. DOI: 10.1007/s00213-017-4690-x
18. Konakanchi S, Raavi V, Ml HK, Shankar V. Impact of chronic sleep deprivation and sleep recovery on hippocampal oligodendrocytes, anxiety-like behavior, spatial learning and memory of rats. Brain Research Bulletin. 2023 Feb 1; 193: 59-71. DOI: 10.1016/j.brainresbull.2022.12.002
19. Chavhan SG, Brar RS, Banga HS, Sandhu HS, Sodhi S, Gadhave PD, Kothule VR, Kammon AM. Clinicopathological studies on vitamin D3 toxicity and therapeutic evaluation of Aloe vera in rats. Toxicology international. 2011 Jan; 18(1): 35. DOI: 10.4103/0971-6580.75851
20. Kim SH, Lee MG. Pharmacokinetics of ipriflavone, an isoflavone derivative, after intravenous and oral administration to rats: hepatic and intestinal first-pass effects. Life sciences. 2002 Feb 1; 70(11): 1299-315. DOI: 10.1016/s0024-3205(01)01508-9
21. Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nature protocols. 2006 Aug; 1(2): 848-58. DOI: 10.1038/nprot.2006.116
22. Nunez J. Morris water maze experiment. Journal of visualized experiments: JoVE. 2008 Sep 24(19): 897. DOI: 10.3791/897
23. Spijker S. Dissection of rodent brain regions. Neuroproteomics. 2011:13-26. DOI: 10.1007/978-1-61779-111-6_2
24. Rahman I, Kode A, Biswas SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nature protocols. 2006 Dec; 1(6): 3159-65. DOI: 10.1038/nprot.2006.378
25. Nwogueze BC, Ojieh AE, Aloamaka CP, Igweh JC, Onyesom I. Levels of glutathione-related antioxidants in some tissues of stressed Wistar rats. Indian Journal of Physiology and Pharmacology. 2021 Dec 8; 65(3): 167-76. DOI:10.25259/IJPP_41_2020
26. Agrawal S, Flora G, Bhatnagar P, Flora SJ. Comparative oxidative stress, metallothionein induction and organ toxicity following chronic exposure to arsenic, lead and mercury in rats. Cellular and Molecular Biology. 2014 Jun 22; 60(2): 13-21. DOI: 10.14715/cmb/2014.60.2.3
27. Ellman GL. Tissue sulfhydryl groups. Archives of biochemistry and biophysics. 1959 May 1; 82(1): 70-7. DOI: 10.1016/0003-9861(59)90090-6
28. Gwarzo MY, Ahmadu JH, Ahmad MB, Dikko AU. Serum glucose and malondialdehyde levels in alloxan induced diabetic rats supplemented with methanolic extract of tacazzea apiculata. International journal of biomedical science: IJBS. 2014 Dec; 10(4): 236. DOI:10.59566/IJBS.2014.10236
29. Keser A, Nesil T, Kanit L, Pogun S. Brain nitric oxide metabolites in rats preselected for nicotine preference and intake. Neuroscience Letters. 2013 Jun 17; 545: 102-6. DOI: 10.1016/j.neulet.2013.04.027
30. Kondamudi PK, Kovelamudi H, Nayak PG, Rao MC, Shenoy RR. Curcumin half analog modulates interleukin-6 and tumor necrosis factor-alpha in inflammatory bowel disease. Pharmacognosy Magazine. 2015 Oct; 11: S296. DOI: 10.4103/0973-1296.165991
31. Ellman GL, Courtney KD, Andres Jr V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology. 1961 Jul 1; 7(2): 88-95. DOI: 10.1016/0006-2952(61)90145-9
32. Gage GJ, Kipke DR, Shain W. Whole animal perfusion fixation for rodents. Journal of visualized experiments: JoVE. 2012; Jul 30(65): 3564. DOI: 10.3791/3564
33. Rajaram C, Nelson Kumar S, Sheeba Tabassum SS, Manohar R, Sumanjali C. Neuroprotective Activity of the Methanolic Extract of Indigofera aspalathoides against Scopalamine induced Alzheimer's Disease in Experimental Rats. Res J Pharm Technol. 2021; 14(10): 5163-8.
34. Haritha P H, Lakshmi Narayanan T, Amrita Babu, Ariharasivakumar G, Dithu Thekkekkara. Evaluation of Anti-amnesic activity of Ayurvedic formulation Saraswathaghrita in the scopolamine-induced rat model. Res J Pharm Technol. 2023; 16(8): 3658-4.
35. Nagaraju Bandaru, Chandrasekhar Komavari, Uma Sankar Gorla, GSN Koteswarao, Umasankar Kulandaivelu, A. Ankarao. Neuroprotective effect of Conessinin on Elevated oxidative stress induced Alzheimers’disease in rats. Res J Pharm Technol. 2020; 13(6): 2703-2707.
36. Sravanthi Kuruvella, Narsimha Reddy Yellu. Naringi crenulata leaf extract alleviates Beta Amyloid Protein Induced Alzheimers disease in mice. Res J Pharm Technol. 2024; 17(6): 2732-8.
37. Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. InSeminars in neurology 2005 Mar ; 25( 01):117-129. DOI: 10.1055/s-2005-867080
38. Sumanth ME, Sowmya H, Nagaraj SV, Narasimharaju K. Efficacy of donepezil and galantamine in retrograde amnesia. Asian J Pharm Clin Res. 2010; 3(4): 23-5.
39. Landel V, Millet P, Baranger K, Loriod B, Féron F. Vitamin D interacts with Esr1 and Igf1 to regulate molecular pathways relevant to Alzheimer’s disease. Molecular neurodegeneration. 2016 Dec; 11: 1-22. DOI: 10.1186/s13024-016-0087-2
40. Klein AB, Williamson R, Santini MA, Clemmensen C, Ettrup A, Rios M, Knudsen GM, Aznar S. Blood BDNF concentrations reflect brain-tissue BDNF levels across species. International Journal of Neuropsychopharmacology. 2011 Apr 1; 14(3): 347-53. DOI: 10.1017/S1461145710000738
41. Shovit Ranjan, Praveen Kumar Sharma. Association of Brain-Derived Neurotrophic factor (BDNF) gene SNP G196A with Type 2 Diabetes and Obesity: A Meta- Analysis. Res J Pharm Technol. 2017; 10(12): 4297-4305.