Coumarins as Emerging Agents in Neurodegenerative Disease Management

Abstract— Neurodegenerative diseases (NDs), including Alzheimer’s, Parkinson’s, and Huntington’s diseases, are debilitating disorders characterized by progressive neuronal loss. These conditions are challenging to treat due to their multifactorial etiology, including genetic, environmental, and oxidative stress-related factors. Recent studies indicate that coumarins (CONs), a class of naturally occurring phytochemicals, may exhibit promising neuroprotective effects against NDs. These compounds demonstrate multiple biological activities, such as neuronal protection, anti-inflammatory effects, and mitigation of oxidative stress, by modulating the underlying molecular pathways. This review summarizes the neuroprotective mechanisms of CONs, with a focus on preclinical studies demonstrating their efficacy in reducing oxidative stress and promoting neuronal survival. Additionally, the review discusses the structural diversity of CONs, highlighting its impact on pharmacokinetics and bioavailability. Moreover, it addresses the modulation of signaling pathways, including MAPK and PI3K/Akt, which contribute to neuroregeneration and neuroprotection. Despite encouraging preclinical evidence, the clinical translation of CON-based therapies faces significant challenges, including poor bioavailability, insufficient clinical trials, and variability in therapeutic responses. Future research should prioritize rigorous clinical studies, interdisciplinary collaboration, and the design of CON derivatives with improved pharmacokinetic properties. Overall, this review underscores the potential of natural compounds such as CONs in developing innovative neurotherapeutic strategies for combating neurodegenerative diseases.