Extraction Optimization and Preliminary Neuroprotective Evaluation of Asiaticoside and Asiatic Acid from Centella asiatica (L.) Urb Using In Vitro and In Silico Approaches

Neurodegenerative diseases are closely associated with chronic neuroinflammation and oxidative stress. Centella asiatica (L.) Urb. is a medicinal plant with recognized cognitive-enhancing and neuroprotective properties. This study optimized the extraction of asiaticoside (AS) and asiatic acid (AA) using an aqueous–ethanol system guided by Hansen solubility parameters (HSP) and evaluated their antioxidant and neuroprotective activities through in vitro and in silico approaches. HSP predictions identified 60% ethanol as the optimal solvent, yielding 9.94 ± 0.24 mg/g dry weight of AS and 3.26 ± 0.07 mg/g dry weight of AA. The extraction method demonstrated favorable sustainability and applicability, with AGREEprep™ and Blue Applicability Grade Index scores of 0.68 and 72.5, respectively. The 60% ethanol extract contained 7.61 ± 0.24 mg gallic acid equivalents/g total phenolics and 22.64 ± 3.71 mg quercetin equivalents/g total flavonoids and exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity with an IC50 of 0.12 ± 0.01 mg/mL. In an Aβ42-induced (Amyloid-β42) SH-SY5Y cell model, the extract, AS, and AA increased cell viability to 80.21 ± 10.62%, 75.92 ± 2.43%, and 92.81 ± 1.90%, respectively. ELISA and molecular docking analyses indicated putative interactions with TNF-α, IL-18, HO-1 and caspase-3. AS and AA are predicted to be involved in modulating neuroinflammation, oxidative stress, and apoptosis, suggesting their potential neuroprotective applications.