Comparative Study of Young and Mature Dendropanax morbifera Leaves: Superior Neuroprotective Efficacy of Young Leaves Through Enhanced Anti-Inflammatory and Metabolic Modulation

Neuroinflammation, driven by microglial activation and oxidative stress, is a key pathological feature of various neurodegenerative diseases. Dendropanax morbifera Léveille (DM) is a medicinal plant known for its diverse pharmacological activities; how-ever, the influence of leaf developmental stage on its neuroprotective potential remains poorly understood. In this study, we compared the phytochemical profiles of young DM (YDM) and mature DM leaves and evaluated their effects on neuronal metabolism and microglia-mediated neuroinflammation. HPLC analysis revealed that YDM contained approximately 2.4-fold higher levels of chlorogenic acid than DM, while DM exhibited higher quercetin content. In differentiated N2A neuronal cells, YDM treatment significantly upregulated the expression of key metabolic and mitochondrial regulators, including PGC-1α, PPARγ, and CPT2, suggesting an enhanced capacity for mitochondrial biogenesis and fatty acid β-oxidation. Under inflammatory conditions, YDM more potently suppressed the secretion of pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-stimulated BV2 microglia compared to DM. Further-more, in N2A cells treated with a BV2–conditioned medium, both extracts effectively mitigated reactive oxygen species production and restored brain-derived neurotrophic factor expression. These findings demonstrate that leaf age is a critical determinant of the phytochemical composition and biological activity of DM. Our results suggest that chlorogenic acid-rich YDM preparations may offer superior therapeutic advantages in targeting neuroinflammatory and metabolic dysregulation in the central nervous system.