ABSTRACT:
Memory and cognitive functions are essential for daily life, with disruptions leading to significant neurodegenerative and psychiatric conditions. Cognitive dysfunction arises from various pathophysiological mechanisms, including neurotransmitter imbalance, impaired cerebral blood flow, oxidative stress, and reduced synaptic plasticity. Nootropics, also known as cognitive enhancers, have gained attention for their potential to improve memory, attention, and learning by targeting these mechanisms. These agents’ activity via diverse pathways such as cholinergic enhancement, neuroprotection, mitochondrial support, and modulation of neurotrophic factors. Synthetic nootropics like donepezil and piracetam are commonly used, although they may present side effects. In contrast, natural nootropics derived from medicinal plants like Bacopa monnieri, Gingko biloba, and Panax ginseng offer neuroprotective effects with potentially better safety profiles. Experimental models including pharmacological, in vivo, in vitro, and in silico approaches are vital for evaluating the efficacy and mechanisms of nootropic agents. Advances in computational methods and omics technologies have accelerated plant-based drug discovery, enabling better understanding of molecular mechanisms and synergistic effects of phytoconstituents. Despite progress, challenges persist, including standardization of plant extracts, poor bioavailability, and lack of rigorous clinical validation. This review highlights the classification, mechanisms, and evaluation models of nootropics, while discussing the challenges and opportunities in herbal cognitive enhancer development. Bridging traditional knowledge with modern scientific approaches hold promise for the discovery of safe and effective nootropic agents.
Cite this article:
A. Snigdhasri, Zeenath Banu. Nootropics: Mechanistic Insights, Experimental Models and Advances in Herbal Drug Discovery. Research Journal of Pharmacology and Pharmacodynamics. 2026; 18(1): 87-3. doi: 10.52711/2321-5836.2026.00011
Cite(Electronic):
A. Snigdhasri, Zeenath Banu. Nootropics: Mechanistic Insights, Experimental Models and Advances in Herbal Drug Discovery. Research Journal of Pharmacology and Pharmacodynamics. 2026; 18(1): 87-3. doi: 10.52711/2321-5836.2026.00011 Available on: https://rjppd.org/AbstractView.aspx?PID=2026-18-1-11
REFERENCES:
1. More et al. Evaluation of Nootropic Effects of Aqueous Extract of Tridax procumbens Linn on Cognitive Functions in Mice. Research Journal of Life Sciences, Bioinformatics, Pharmaceutical and Chemical Sciences. 2018 Nov-Dec; 2454-6348. doi:10.26479/2018.0406.18
2. Bhosale SS, Kumar S S, Jamadagni S, Arulmozhi S. Therapeutic potential of Bhiramiyadhi bhavanai choornam in ameliorate 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
3. Reddy N et al. Evaluation of nootropic activity of Curcuma longa leaves in diazepam and scopolamine induced amnesic mice and rats. International Journal of Basic and Clinical Pharmacology. 2015 Aug; 4(4): 714-719. doi: 10.18203/2319-2003.ijbcp20150378
4. K Singh et al. Pharmacological investigation of Achras sapota against scopolamine induce amnesia and cognitive impairment in laboratory animals. Toxicology Reports 13 2024 Nov;2214-7500.
5. Tiwari DK, Upmanyu N. Evaluation of nootropic activity of Semecarpus anacardium leaves in rodents. International Journal of Pharmaceutical Sciences and Research. 2021Feb; Vol 12(2): 1310-1319. doi:10.13040/IJPSR. 0975-8232.12(2).1310-19
6. Mali et al. Evaluation of nootropic activity of Limonia acidissima against scopolamine induced amnesia in rats. Turk J Pharm Sci. 2021; 18(1):3-9. doi: 10.4274/tips.galenos.2019.30316
7. Mahadik VJ et al. Cognition Enhancing potential of Sesbania grandiflora fruit extract in scopolamine induced amnesia in mice. Research J. Pharm. And Tech. 2020; 13(11): 5057-5062. doi:10.5958/0974-360X.2020.00886.0
8. 8.Balasubramanian C, Ramaswamy R S. Evaluation of nootropic and neuroprotective properties of Siddha drug Poorna Chandrothaya Chenthuram (PCC) in scopolamine induced amnesia in mice. Phytomedicine Plus 4. 2024 June. doi: 10.1016/j. phyplup2024.100585
9. Zhang L, Jin C, Lu X, Yang J, Wu S, Liu Q, Chen R, Bai C, Zhang D, Zheng L, Du Y Cai Y. Aluminium chloride impairs long- term memory and downregulates cAMP-PKA-CREB signalling in rats. Toxicology. 2014 Sep.
10. Rahman A, Banu Z, Rani R, Mehdiya R. Unravelling Alzheimer’s disease: insights into pathophysiology, etiology, diagnostic approaches, and the promise of aducanumab, lecanemab, and donanemab. J Phytonanotechnology Pharm sci. 2024; 4,1-10.
11. Chaturvedi S, Ganeshpurkar A, Shrivastava A, Dubey N. Protective effect of co- administration of caffeine and piracetam on scopolamine induced amnesia in Wristar rats. Current Research in Pharmacology and Drug Discovery. 2021 Aug.
12. Team, B. (2025). Anti-cholinesterases Mechanism of Action in Alzheimer's Disease (AD). https://app.biorender.com/biorender-templates/details/t-65141eecba95ae765b23241a-anti-cholinesterases-mechanism-of-action-in-alzheimers-disea
13. Alshabi AM, ShaikhIA, Savant C. Nootropic and Neuroprotective effects of ethanol extract of Vateria indica L bark on scopolamine induced cognitive deficit in mice. Tropical Journal of Pharmaceutical Research. 2020 Mar; 19 (3): 587-594.
14. Kumar P, Singh A P, Kaur G, Sharma S, Sharma A K, Kaur K. Exploring the nootropic effect of Junipers recurva extract: Possible involvement of acetylcholinesterase inhibiton. Department of Pharmaceutical Sciences. 2019 Jul- Sep; 13 (3).
15. Saini S, Choudhary M, Garg A. Investigation of nootropic potential of ethanol extract of Elettaria cardamomum Maton fruit (Cardamom): a spice of India. Clinical Phytoscience. 2021; 7:68.
16. Kumar S, Maheshwari KK, Singh V. Protective effects of Punica granatum seeds extract against aging and scopolamine induced cognitive impairments in mice. Afr. J. Traditional, Complementary and Alternative Medicines. 2009; 6 (1): 49-56.
17. Lakshmi. K et al. Terminalia chebula Retz improve memory and learning in Alzheimer’s Model: (Experimental Study in Rat). Research J. Pharm. And Tech 2018; 11(11):4888-4891. Doi:10.5958/0974-360X.2018.00890.9
18. Sulabh G et al. Study comparing the effect of topiramate and pregabalin on learning and memory with phenytoin in albino rats using Morri’s water maze and elevated plus maze. Research Journal of Pharmacy and Technology 2023; 16(7):3451-5. Doi:10.52711/0974-360X.2023.00570.
19. Kumar M N, Virender K. Evaluation of Nootropic Activity of Carica papaya in mice. Biolife An International Quarterly Journal of Biologyand Life Sciences. 2014; 2(3): 721-730.
20. Flood JF, Morley JE (1998) Learning and memory in the SAMP8 mouse. Neurosci Biobehav Rev 22:1-20.
21. Gawande DY, Goel RK. Pharmacological validation of in silico guided novel nootropic potential of Achyranthes aspera L. Journal of Ethnopharmacology. 2015 Dec: 324-334.
22. Athitya L.V.S et al. Screening of Gracilaria Corsicana Extracts for Acetylcholinesterase Inhibitory Activity. Research J. Pharm. And Tech 2018; 11(9): 3848-3850. Doi:10.5958/0974-360X.2018.00704.7
23. Kumar, A., Singh, A., 2015. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol. Rep. 67 (2), 195–203.
24. Mathiasen, J.R., DiCamillo, A., 2010. Novel object recognition in the rat: a facile assay for cognitive function. Curr. Protoc. Pharmacol. 49 (1), 5–59.
25. Rahman A, Banu Z. Impact of Aluminium Chloride (AlCl3) on brain function: A Review of Neurotoxic Mechanisms and Implications for Alzheimer’s Disease. Trends in Pharmaceutical Sciences and technologies. 2024, 10 (4), 355-366.
26. Banu Z, Poduri RR, Kumar S, Bhattamisra. Phytochemical profiling, in silico molecular docking and ADMET prediction of alkaloid rich fraction of Elaeocarpus angustifolius blume seeds against Alzheimer’s. Natural Product Research. 2025, 1-9.
27. Mesquita, S., Ferreira, A.C., Sousa, J.C., Correia-Neves, M., Sousa, N., Marques, F., 2016. Insights on the pathophysiology of Alzheimer's disease: the crosstalk between amyloid pathology, neuroinflammation and the peripheral immune system. Neurosci. Biobehav. Rev. 68, 547–562.
28. Saraceno, C., Musardo, S., Marcello, E., Pelucchi, S., Diluca, M., 2013. Modeling Alzheimer's disease: from past to future. Front. Pharmacol. 4, 77.