Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of the central nervous system that leads to cognitive decline and memory loss (Parihar et al., 2004). According to a report from the World Health Organization, over 55 million people suffer from dementia (Alzheimer’s Association, 2019). AD is associated with decreased levels of the neurotransmitter acetylcholine, which is broken down by the enzyme acetylcholinesterase (AChE) in synaptic clefts (Pohanaka et al., 2012). The reduction in AChE activity results in an accumulation of acetylcholine, which is thought to be a compensatory response due to the loss of cholinergic neurons, leading to synaptic dysfunction and cognitive deficits (Scarpini et al., 2003). Increasing brain acetylcholine levels by inhibiting AChE is a critical strategy in AD treatment. However, current AChE inhibitors, such as donepezil, galantamine, and rivastigmine, are associated with side effects and low bioavailability (Kelly et al., 1997; Gottwald et al., 1998; Scott et al., 2000). Therefore, there is a pressing need to discover more effective AChE inhibitors from natural sources with fewer side effects.
Plant bioactive components, such as alkaloids, phenolics, terpenoids, and flavonoids, play essential roles in plant defense against biotic and abiotic stressors and enhance plant resistance to pathogens and diseases (Pan et al., 2019). Several medicinal plants, including turmeric (Sharifi et al., 2020), Withania somnifera (Dar et al., 2020), and Bacopa monnieri (Abdul et al., 2019), have shown anti-neuronal properties in preclinical and clinical studies, suggesting potential therapeutic effects against neurodegenerative diseases like AD. One such medicinal herb is Momordica charantia, belonging to the Cucurbitaceae family, which has demonstrated anti-diabetic, anti-helminthic, antioxidant, anti-inflammatory, antimicrobial, and neuroprotective activities (Pereira et al., 2016; Sheeja et al., 2012). Previous studies have indicated that Momordica charantia, also known as bitter melon, can enhance neurotransmitter levels and synaptic plasticity by inhibiting AChE, thereby improving neurotransmission and cognitive performance in AD (Pan et al., 2019). Despite numerous attempts to isolate bioactive compounds from natural sources, comprehensive studies are still needed to determine their molecular interactions.
Molecular docking is a crucial tool in computational biology and medicinal chemistry for predicting and analyzing ligand-protein interactions. It helps understand binding mechanisms and identify high-affinity ligands, playing a vital role in early drug discovery and the development of novel therapeutic agents (Saklani et al., 2008). While several studies have used in vivo and in vitro models to investigate AChE as a biomarker in neurodegenerative diseases (Choi et al., 2016), the specific compounds that effectively inhibit AChE remain to be fully elucidated (Vijayakumar et al., 2018). Recent research has employed molecular docking methods to study the interaction and conformation of ligands with AChE, yet many bioactive compounds remain unexplored.
The main focus of our study is to explore various phytocompounds of Momordica charantia as potential therapeutic agents against AChE, a biomarker associated with neurodegenerative diseases like AD. Extracts of Momordica charantia have bioactive compounds that effectively inhibit acetylcholinesterase activity, hence showing neuroprotective benefits and other possibilities that may help in the slowing or preventing of the development of Alzheimer's disease. Our study to investigate Extracts of Momordica charantia have bioactive compounds that effectively inhibit acetylcholinesterase activity, hence showing neuroprotective benefits and other possibilities that may help in the slowing or preventing of the development of Alzheimer's disease screens nineteen essential bioactive phytocompounds of M. charantia using molecular docking to evaluate their efficacy against AChE. Understanding ligand-protein interactions and the inhibitory activity of these compounds against AChE will contribute to the drug design and development process for treating neurodegenerative diseases like AD.