Optimized extraction and purification of geniposidic acid from Eucommia ulmoides leaves and its Anti-Parkinson's disease activity

This study presents a scalable and efficient approach for extracting the bioactive iridoid compound geniposidic acid (GPA) from Eucommia ulmoides leaves ( E . ulmoides leaves) by optimizing an ultrasound-assisted extraction process using response surface methodology (RSM). Under the optimized conditions—which include a 49 % ethanol volume fraction, a solid-to-liquid ratio of 1:25 g/mL, a 60 min extraction time, and a temperature of 60 °C—the GPA yield reached 10.53 ± 0.14 mg/g. Following this, a systematic evaluation of macroporous resins based on adsorption and desorption performance identified H103 resin as the most suitable purification medium. Using this resin, the optimized chromatographic process achieved an adsorption efficiency of 96 %. After impurities were removed with 4 bed volumes (BV) of purified water, gradient elution with 6 BV of 5 % ethanol produced a GPA-enriched fraction with a purity of 16.53 ± 0.43 %, representing a 6.43-fold increase compared to the initial extract. Further purification via preparative high-performance liquid chromatography (Prep-HPLC) yielded a GPA monomer with over 95 % purity. To validate its biological activity, in vivo testing was conducted using a Caenorhabditis elegans ( C. elegans ) model of Parkinson’s disease (PD). The results showed that high-purity GPA significantly enhanced the health status of C. elegans , effectively suppressed the abnormal aggregation of α-synuclein (α-syn), and mitigated both acute and chronic dopaminergic neuronal damage. This study provides a robust scientific foundation for the large-scale production of GPA and highlights its promising neuroprotective potential. • An efficient purification process for geniposidic acid was developed using Eucommia ulmoides leaves. • The value-added transformation and utilization of the agricultural byproduct, Eucommia ulmoides leaves, was achieved. • Geniposidic acid was shown to possess significant neuroprotective potential. • A novel strategy was established for the high-value utilization of Eucommia ulmoides Oliv. as a bioactive resource.