Rungta Institute of Pharmaceutical Sciences, Kohka, Kurud, Bhilai,(C.G.), India
Neurodegenerative disorders such as Alzheimer’s disease are characterized by slowly memory loss and cognitive impairment , and the currently available pharmacological treatments provide only limited symptomatic benefits. Merremia dissecta is a medicinal plant traditionally used for various therapeutic purposes and has been reported to possess antioxidant, anti-inflammatory, and neuroprotective effects . Scopolamine-induced cognitive dysfunction is a wellestablished experimental model that mimics cholinergic deficits identified in Alzheimer’s disease. This review summarizes existing literature on the phytochemical constituents of Merremia dissecta leaves, including flavonoids, phenolic compounds, alkaloids, and glycosides, and discusses their possible mechanisms of action such as antioxidant activity, inhibition of acetylcholinesterase, and modulation of neuroinflammatory pathways. Overall, the reviewed evidence suggests that Merremia dissecta leaves may offer promising neuroprotective effects against scopolamine-induced memory impairment, warranting further experimental and clinical investigations
Dementia is a broad clinical term used to describe a progressive decline in a cognitive ability, including memory, reasoning, and other intellectual functions (1). This deterioration gradually disrupts an individual’s ability to perform occupational tasks and participate in social interactions. Among the many forms of dementia, Alzheimer’s disease (AD) is the most common and indicates a progressive neurodegenerative disorder. It is generally identified by memory impairment accompanied by behavioural and psychological disturbances, which significantly impact with activities of involved in daily life. Alzheimer’s disease accounts for nearly 70% of dementia cases worldwide (3). The pathological progression of AD involves several interconnected mechanisms, including degeneration of cholinergic neurons, abnormal tau protein phosphorylation, and accumulation of β-amyloid peptides in the brain (1). Research indicates that reduced levels of acetylcholine (ACh), a key neurotransmitter involved in learning and memory, are closely related with cognitive dysfunction (4). Furthermore, elevated activity of acetylcholinesterase (AChE), the enzyme responsible for ACh breakdown, has been reported in individuals with AD. Clinically, AD manifests as memory loss, difficulty in planning and problem-solving, impairments in language and communication, inability to perform routine tasks, spatial disorientation, and behavioural changes such as anxiety, depression, and mood disturbances (1,3). As AD advances, these symptoms progressively intensify (10). Diagnosis is typically based on a combination of clinical evaluation, detailed medical and family history, cognitive and behavioural assessments, physical and neurological examinations, laboratory investigations, and neuroimaging techniques (1, 11). Early cognitive decline has been strongly associated with cholinergic dysfunction within the hippocampus and cerebral cortex, brain regions essential for learning and memory processes (11).
In addition to cognitive impairment, neuropsychiatric symptoms such as depression, apathy, aggression, and psychosis commonly occur in AD and share overlapping pathological pathways, although each also possesses distinct mechanisms (10). To study dementia and related cognitive deficits, various experimental animal models have been developed based on different pathogenic features. One widely used model involves scopolamine, a muscarinic receptor antagonist that disrupts central cholinergic neurotransmission. Administration of scopolamine in rodents induces learning and memory deficits by impairing cholinergic signalling, thereby closely resembling the cholinergic neuronal loss observed in the AD brain. By blocking acetylcholine binding at muscarinic receptors, scopolamine alters neurotransmitter balance, damages hippocampal neurons, and ultimately results in cognitive dysfunction (18). Currently, no definitive cure exists for dementia-related disorders, and available pharmacological treatments provide only limited symptomatic relief while being associated with various adverse effects (3). Consequently, there is increasing interest in alternative therapeutic approaches. Medicinal plants possessing antioxidant and anti-inflammatory properties are considered promising candidates for attenuating cognitive decline (3,6). Merremia dissecta, a medicinal plant belonging to the family Convolvulaceae, has been traditionally used for the treatment of inflammatory conditions and other ailments, and its pharmacological properties suggest potential neuroprotective benefits.
Figure 1—Differences between a healthy brain and a brain with Alzheimer type
DISEASE PROGRESSION AND STAGES:-
Alzheimer’s disease typically develops three major stages: early (mild), middle (moderate), and late (severe). Each stage shows increasing cognitive decline and dependence on caregivers, though progression varies among individuals (15).
1. Early (Mild) Stage
2. Middle (Moderate) Stage
3. Late (Severe) Stage
(15).
Figure 2. - Stages of Alzheimer’s disease
PATHOPHYSIOLOGY OF ALZHEIMER DISEASE :-
The human brain contains billions of neurons, each composed of a cell body, an axon, and multiple dendrites. For normal functioning, neurons rely on effective communication, nutrient uptake, and self-repair mechanisms (3). In Alzheimer’s disease (AD), these essential neuronal processes are severely disrupted. Two key pathological features of AD are neuritic (β-amyloid) plaques and neurofibrillary tangles (NFTs).
Neuritic plaques are formed by the abnormal accumulation of β-amyloid protein fragments in the extracellular space between neurons (16). These β-amyloid peptides originate from the amyloid precursor protein (APP), a transmembrane protein present in neuronal membranes. APP is cleaved by enzymes such as βsecretase and γ-secretase, producing neurotoxic β-amyloid fragments, particularly Aβ42 (11). These fragments aggregate and form insoluble plaques, which interfere with synaptic communication and neuronal function. Plaque formation is especially prominent in the hippocampus and cortical regions of the brain that are critical for learning and memory.
Neurofibrillary tangles represent the second key pathological feature of AD and develop within neurons. Normally, microtubules form part of the neuronal cytoskeleton and are stabilized by a protein known as tau. In Alzheimer’s disease, tau undergoes abnormal hyperphosphorylation, leading to microtubule destabilization. The altered tau proteins aggregate inside neurons, forming neurofibrillary tangles that disrupt intracellular transport and ultimately cause neuronal dysfunction and death (16). As Alzheimer’s disease progresses, extensive neuronal loss occurs in several brain regions, particularly within the limbic system, including the hippocampus and amygdala (16). This widespread neuronal degeneration results in visible brain atrophy, characterized by a reduction in brain volume, narrowing of cortical folds and grooves, and enlargement of the ventricles compared to a healthy brain (1).
Figure 3.- Pathophysiology of Alzheimer disease
SCOPOLAMINE-INDUCED MEMORY IMPAIRMENT MODEL:-
Scopolamine, also referred to as hyoscine or levo-duboisine, is a naturally occurring alkaloid with potent antimuscarinic properties. It is a secondary metabolite predominantly found in plants belonging to the Solanaceae (nightshade) family. Pharmacologically, scopolamine acts as a competitive antagonist at muscarinic acetylcholine receptors, with a high affinity for the M1 receptor subtype. (19) Due to its ability to disrupt cholinergic neurotransmission, scopolamine is widely used as a standard or reference compound for inducing reversible amnesia in both humans and experimental animals (5). The cognitive impairments produced by scopolamine are commonly attributed to a functional deficiency of acetylcholine, supporting the hypothesis that cholinergic signaling plays a crucial role in learning and memory processes (12).
In addition to its effects on memory and learning, scopolamine also alters several behavioral parameters, including locomotor activity, attention, anxiety-related behavior, and overall cognitive performance. (19)
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Figure 4.- Mechanism of scopolamine-induced memory impairment through muscarinic acetylcholine receptor blockade leading to cholinergic dysfunction.
IMPORTANCE IN SCREENING NEUROPROTECTIVE COMPOUNDS:-
The scopolamine model is extensively used to screen and validate the efficacy of anti-Alzheimer’s agents, including cholinesterase inhibitors such as donepezil and rivastigmine, as well as plant-derived compounds with antioxidant and antiinflammatory properties(5). Several herbal extracts rich in flavonoids, phenolic compounds, terpenoids, and alkaloids have demonstrated significant potential in reversing scopolamine-induced learning and memory deficits (6).
Advantages of the Scopolamine Model - • Simple to perform and highly reproducible.
Limitations of the Scopolamine Model -
Despite its usefulness, the scopolamine model has certain drawbacks:
Therefore, although the scopolamine-induced model is highly valuable for preliminary screening of cognitive enhancers and neuroprotective agents, findings should be complemented with additional experimental models for a more comprehensive evaluation.
MECHANISM OF NEUROPROTECTIVE ACTION :-
Neuroprotection refers to the capacity of a substance to safeguard neuronal integrity and functionality by delaying or preventing neurodegenerative changes. In conditions such as Alzheimer’s disease and scopolamine-induced cognitive dysfunction, neuronal damage arises from multiple interrelated mechanisms, including impaired cholinergic transmission, oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, and apoptosis. Medicinal plants rich in bioactive phytochemicals exert neuroprotective effects by targeting several of these pathological pathways simultaneously (6). The neuroprotective potential of Merremia dissecta leaf extract is believed to result from the combined and synergistic actions of its phytoconstituents on multiple molecular targets.
The cholinergic system play crucial role in learning and memory functions. Scopolamine produces cognitive impairment by antagonizing muscarinic acetylcholine receptors, thereby reducing cholinergic neurotransmission. Neuroprotective agents counteract this effect by improving acetylcholine availability and receptor activity. (20)
Merremia dissecta leaf extract may enhance cholinergic function through inhibition of acetylcholinesterase (AChE), the enzyme responsible for acetylcholine breakdown. The presence of flavonoids and phenolic compounds in the leaves has been associated with AChE inhibitory activity, leading to increased acetylcholine levels in synaptic spaces (13) . Improved cholinergic transmission supports memory retention, synaptic plasticity, and cognitive performance, particularly in scopolamine-induced models.
Oxidative stress plays a central role in neuronal injury associated with neurodegenerative disorders. Scopolamine increases reactive oxygen species (ROS) production, resulting in lipid peroxidation, protein oxidation, and DNA damage (5) . These processes compromise neuronal membrane stability and disrupt neurotransmission.
The neuroprotective efficacy of Merremia dissecta is closely linked to its antioxidant capacity. The leaves are rich in flavonoids, phenolic compounds, and terpenoids that effectively scavenge free radicals. These phytochemicals reduce lipid peroxidation and strengthen endogenous antioxidant defenses such as superoxide dismutase, catalase, and reduced glutathione. Restoration of oxidative balance protects neurons from damage and helps preserve cognitive function (13,14).
The neuroprotective effects of Merremia dissecta cannot be attributed to a single compound. Instead, the combined action of flavonoids, phenolic acids, alkaloids, and terpenoids produces a synergistic effect that enhances antioxidant, antiinflammatory, and cholinergic modulatory activities. This multi-target mechanism is particularly advantageous in complex neurodegenerative disorders such as Alzheimer’s disease (13,14).
PLANT PROFILE -
MERREMIA DISSECTA
Botanical Description -
Figure 5.- Merremia dissecta
Taxonomical classification of M. dissecta—
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Kingdom |
Plantae |
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Subkingdom |
Tracheobionta |
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Superdivision |
Spermatophyta |
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Division |
Magnoliophyta |
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Class |
Magnoliopsida |
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Subclass |
Asteridae |
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Order |
Solanales |
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Family |
Convolvulaceae |
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Genus |
Merremia Dennst. ex Endl. |
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Species |
Merremia dissecta (Jacq.) Hallier f. |
Vernacular names of M. Dissecta.
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Nagin |
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Kaliaphumari |
PHYTOCHEMICAL CONSTITUENTS OF MERREMIA DISSSECTA
LEAVES :-
Phytochemical investigation reveal the presence of bioactive compound such as-
These constituents are well-known for their neuroprotective, antioxidant, and anti-inflammatory activities, analgesic activity, and other activities (13,14 ).
DISCUSSION
The present review focuses on the neuroprotective potential of Merremia dissecta leaves against scopolamine-induced memory impairment, a widely used experimental model for studying Alzheimer’s-like cognitive dysfunction. Alzheimer’s disease is a complex disorder involving multiple pathological mechanisms, and current drug therapies mainly provide temporary symptomatic relief (3). Therefore, plant-based medicines with multitarget actions are gaining increasing attention as alternative treatment options (3,6). The literature reviewed suggests that scopolamine produces memory impairment by blocking muscarinic acetylcholine receptors, leading to reduced cholinergic transmission in the brain (5). This mechanism closely resembles the cholinergic deficit observed in Alzheimer’s disease, making the scopolamine model suitable for preliminary screening of neuroprotective agents. Several studies have shown that herbal extracts rich in antioxidant and anti-inflammatory compounds can reverse scopolamine-induced cognitive deficits by improving neurotransmitter balance and protecting neuronal cells (6) . Merremia dissecta leaves have been reported to contain a variety of bioactive phytochemicals such as flavonoids, phenolic compounds, alkaloids, and terpenoids. These constituents are known for their ability to scavenge free radicals, reduce oxidative stress, and modulate inflammatory responses in the nervous system(13,14). The combined action of these phytochemicals may contribute to the observed neuroprotective and memory-enhancing effects of Merremia dissecta. Overall, the reviewed studies indicate that Merremia dissecta leaves possess promising neuroprotective properties and may help improve memory impairment through antioxidant and cholinergic mechanisms. However, most of the available evidence is based on experimental models, and direct clinical data remain limited. Further well-designed studies are required to confirm these findings and to establish standardized formulations for clinical use.
CONCLUSION
The present review highlights the neuroprotective potential of Merremia dissecta leaves in the management of memory impairment, particularly in scopolamine-induced cognitive dysfunction. The available literature suggests that the leaves of Merremia dissecta contain important bioactive compounds such as flavonoids and phenolic constituents, which may help protect brain cells through antioxidant, anti-inflammatory, and memory-enhancing actions. The use of scopolamine-induced memory impairment models provides a reliable method for evaluating the effectiveness of neuroprotective agents in Alzheimer’s-like conditions. Overall, Merremia dissecta leaves appear to be a
promising natural source for the development of potential neuroprotective
herbal extract for memory-related disorders.
FUTURE SCOPE
Although the reviewed studies show promising neuroprotective effects of Merremia dissecta leaves, further research is required to confirm these findings. Future studies should focus on identifying active compounds, evaluating longterm safety, and conducting clinical trials in humans. Such research may support the development of safe and effective herbal treatments for memoryrelated disorders.
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Yadang FSA, Nguezeye Y, Kom CW, Betote PHD, Mamat A, Tchokouaha
LRY, Taiwé GS, Agbor GA, Bum EN.Scopolamine-Induced Memory
Impairment in Mice: Neuroprotective Effects of Carissa edulis (Forssk.) Valh
(Apocynaceae) Aqueous Extract. Int J Alzheimers Dis. 2020 Aug 31;2020:6372059. Doi: 10.1155/2020/6372059. PMID: 32934845; PMCID: PMC7479457.
Ornamental, and Weed - A Review. Economic Botany, 2007; 61(2): 109-120.
AD.Annual Review of Neuroscience. 2011. DOI: 10.1146/annurevneuro061010-113613
Saumya Helode, Shweta Ram, Gyanesh Kumar Sahu, A Review: Neuroprotective Potential of Merremia Dissecta Leaves Against Scopolamine-Induced Memory Impairment, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 3, 1147-1155. https://doi.org/10.5281/zenodo.18956617
10.5281/zenodo.18956617
