Unlocking the Neuroprotective Potential of Semecarpus anacardium L.-An Updated Review

Neurodegenerative diseases (NDs) pose a significant health burden globally, and this burden is increasing with an ageing population. Despite this challenge, restorative treatments for NDs remain elusive. In these conditions, the brain is vulnerable to oxidative stress and inflammation due to a deficiency or reduction in antioxidative enzymes. Oxidative stress and inflammation damage neuronal cells, leading to neurodegeneration. Various studies have explored the neuroprotective effects of flavonoids in different in vitro and animal models, primarily due to their antioxidative and anti-inflammatory properties. Crude extracts and active metabolites of Semecarpus anacardium L. have shown potential in reversing dysregulated oxidative stress and neuroinflammation. S. anacardium L. extract (SAE) and its phytocomponents, such as butein, anacardic acid, and amentoflavone, have been experimentally demonstrated to modulate oxidative stress and neuroinflammation through coordinated activation of Nrf2-mediated antioxidant pathways and suppression of NF-ĸB-driven inflammatory signaling. At a molecular level, flavonoids from SAE induce the expression of p38 MAPK and Nrf2, as well as antioxidant enzymes. Furthermore, inflammatory genes such as NF-ĸB, MAPK, AP-1, iNOS, and COX-2 are suppressed following treatment with SAE. NF-ĸB inhibition leads to neuroprotection via inhibiting the function of caspase-3 and apoptosis. Overall, this review discusses the protective role of SAE and its phytocomponents in mitigating neuronal oxidative stress, inflammation, and degeneration. Furthermore, this review highlights the translational potential of SAE and its phytocomponents as complementary therapeutic candidates for neurodegenerative disorders. However, variability in extract composition and limited pharmacokinetic characterization remain key barriers to clinical translation.