Therapeutic potential of Echinocactus grusonii and its associated endophytic fungus Aspergillus oryzae in neuroprotection: in vitro and in silico investigations

Abstract

Abstract The Golden Barrel Cactus ( Echinocactus grusonii , syn. Kroenleinia grusonii ), native to Mexico, is well known in horticulture but remains insufficiently studied with respect to its chemical composition. This study examined the chemical profile and neuroprotective potential of Echinocactus grusonii spines and its endophytic fungus, Aspergillus oryzae . The spines contained markedly higher levels of phenolics (293 mg gallic acid/g DW extract), flavonoids (132 mg quercetin/g DW extract), and alkaloids (14.5 mg atropine/g DW extract) compared to the stem. Untargeted metabolomics (UPLC-HRMS/MS) tentatively identified 27 metabolites in the spines and 14 in the fungal extract. Both extracts exhibited potent, dose-dependent inhibition of acetylcholinesterase (AChE) and β -secretase (BACE-1). The spines extract showed IC₅₀ values of 0.362 µg/mL (AChE) and 0.425 µg/mL (BACE-1), while the fungal extract was more effective against AChE (IC₅₀ = 0.255 µg/mL). In silico docking was performed for all identified compounds, and molecular dynamics simulation of the top-scoring candidates demonstrated stable interactions with the target enzymes. These findings highlight the spines of Echinocactus grusonii and their associated endophytes as promising dual-target neuroprotective sources for the management of neurodegenerative disorders.