Sustainable production of alkaloid-enriched extract from Miliusa velutina stem bark: Process optimization, life cycle assessment, and therapeutic potential against inflammation and cancer

This study presents a sustainable framework integrating process optimization, life cycle assessment (LCA), and pharmacological evaluation for recovering alkaloid-rich extract from Miliusa velutina stem bark. Ultrasound-assisted extraction (UAE) was optimized via the face-centered Central Composite Design-Response Surface Methodology (CCD-RSM). Applying the optimal conditions (79.2°C, 18.3 min, 61.3% ethanol, 1:13 w/v solid/liquid ratio) resulted in an experimental yield of 161.00 ± 5.46 mg AE/g extract, which highly corroborated the model's prediction (164.77 mg AE/g extract, R 2 = 0.9990). To align with climate-responsive chemistry, an ISO 14040/14044-compliant LCA was conducted. The LCA validated that the optimized UAE protocol significantly mitigates environmental burdens and energy consumption, offering a sustainable, low-carbon alternative. Beyond eco-efficiency, the optimized extract exhibited potent anti-inflammatory activity by significantly suppressing nitric oxide production in LPS-stimulated RAW264.7 macrophages without inducing cytotoxicity. Furthermore, it demonstrated pronounced, dose-dependent cytotoxicity against SK-LU-1, HepG2, and MKN7 carcinoma cells (IC 50 = 20.75 ± 0.59, 15.63 ± 0.71, and 21.85 ± 0.64 µg/mL, respectively), drastically outperforming its non-optimized extract. These findings highlight that the optimized alkaloid extraction from M. velutina stem bark successfully harmonizes environmental sustainability with pronounced pharmacological efficacy, positioning it as a promising eco-friendly therapeutic agent.