Natural compounds in neuroprotection and nervous system regeneration: a narrative review

The central nervous system is a highly complex and specialized network that regulates essential physiological and behavioral functions. Owing to its limited regenerative capacity, it is particularly susceptible to pathological insults such as trauma, ischemia, and neurodegenerative diseases. In this sense, the search for effective therapies to prevent and repair damage to this system remains a major biomedical challenge. The present study comprises a comprehensive literature search conducted in PubMed database, covering peer-reviewed articles published in English between January 2015 and May 2025. The search combined the reference term "natural compounds" with the keywords "central nervous system, oxidative stress, neuroinflammation, regeneration, and neuroprotection," employing the Boolean operator "AND." Articles were selected according to their relevance to the scope of this work, encompassing both original experimental studies (in vivo and in vitro) as well as literature reviews. Natural compounds derived from plants, fungi, and other biological sources exhibit promising neuroprotective and regenerative properties by modulating multiple cellular and molecular pathways. Key classes of bioactive compounds, such as polyphenols, terpenes, saponins, and alkaloids, as well as standardized plant extracts, are highlighted, emphasizing their multitarget mechanisms and translational potential. These include enhancement of antioxidant defenses (nuclear factor erythroid 2-related factor 2/antioxidant response element), suppression of inflammatory signaling (nuclear factor-kappaB), regulation of apoptosis (Bcl-2 and caspases), promotion of neurotrophic activity (brain-derived neurotrophic factor and nerve growth factor), and restoration of autophagic flux (mammalian target of rapamycin and AMP-activated protein kinase). Current challenges, such as low bioavailability and scarcity of high-quality clinical validation, are also discussed, alongside future perspectives for incorporating natural compounds into central nervous system-directed therapeutic strategies. Altogether, the present work underscores the potential of natural agents to promote neuroprotection and regeneration and supports further investigation into their clinical applicability.