Novel bioprocessing strategies and evaluation models for walnut meal bioactives

This review addresses the challenges in valorizing walnut meal, a by-product of walnut oil extraction, by outlining its key bioactive constituents—proteins/active peptides, polysaccharides, and phenolic compounds—and their health benefits. It examines emerging green processing strategies, including mixed-strain solid-state fermentation, microbe-enzyme synergistic fermentation, and integrated multi-technology approaches. The article also discusses the evolution of efficacy assessment from conventional cellular and animal models toward human biomimetic platforms such as organoids and organs-on-chips, which offer more physiologically relevant models for elucidating functional mechanisms. In contrast to existing reviews focusing on isolated components or conventional techniques, this work constructs an integrated framework spanning from “green synergistic processing” to “human biomimetic evaluation.” It aims to accelerate the translation of walnut-derived bioactive compounds into functional foods and pharmaceuticals, promoting comprehensive, high-value utilization of walnut resources. • Novel processing strategies enhance yield and sustainability of bioactives. • Mixed-strain SSF and enzyme synergy enhances component bioavailability. • Organoid models enable precise human-relevant bioactivity evaluation. • Multi-organ chips holistically assess systemic health benefits of bioactives.