Abstract: Natural active ingredients encompass a diverse array of bioactive compounds, including flavonoids, alkaloids, polyphenols, polysaccharides, and terpenoids. These compounds possess a wide spectrum of potent biological activities, such as antioxidant, anti-inflammatory, anti-tumor, and immunomodulatory effects, making them highly valuable and extensively applied in the fields of modern medicine, functional foods and cosmetics. However, the effective utilization of these compounds is severely hindered by the complexity of their natural sources. Isolating specific targets is an arduous challenge, because they typically exist in extremely low concentrations within complex biological matrices. Furthermore, they frequently coexist with numerous structurally analogous impurities and isomers, which possess close physicochemical properties, significantly increasing the technical difficulty and economic cost of separation and purification. The traditional extraction and separation techniques, such as liquid-liquid extraction and solid-phase extraction, present obvious technical bottlenecks when applied to these complex mixtures. These methods suffer from low selectivity, low efficiency, and high consumption of toxic organic solvents. Consequently, they are not only time-consuming and labor-intensive but also pose significant environmental hazards and health risks. Moreover, they are often unsuitable for large-scale industrial production due to prohibitive costs and strict environmental regulations. To address these critical challenges, molecularly imprinted polymers (MIPs) have attracted significant attention from the scientific community. This advanced technique simulates the highly specific "lock-and-key" mechanism found in natural antigen-antibody or enzyme-substrate interactions. It polymerizes to create complementary cavities, which perfectly match the targets' size and three-dimensional architecture, enabling specific recognition and adsorption of target analytes. MIPs exhibit prominent advantages over traditional materials, including high selectivity, superior chemical stability, ease of preparation, and excellent reusability. Therefore, MIPs have emerged as a crucial and promising technology for the efficient separation and enrichment of natural products. Nevertheless, traditional MIPs typically possess inherent defects that restrict their widespread practical application. The most significant disadvantages include a slow mass transfer rate due to the dense polymer network, limited adsorption capacity, and the difficult elution of templates, which can lead to template leakage. Additionally, traditional MIPs often suffer from insufficient mechanical strength, irregular particle shapes, and a heterogeneous distribution of binding sites, which result in low binding efficiency and poor reproducibility. To overcome these limitations and enhance performance, researchers have recently combined MIPs with various novel functional substrates to create advanced molecularly imprinted composites. Common functional materials employed in these strategies include magnetic nanoparticles for rapid separation, membrane materials for filtration, hydrogels for biocompatibility, and porous frameworks that provide high surface area. The resulting molecularly imprinted composites significantly improve adsorption performance, separation speed, and the accessibility of binding sites. This review systematically discusses the fundamental recognition mechanisms, including the covalent and non-covalent approaches, and common polymerization strategies of molecular imprinting technology. It summarizes the preparation methods, structural characteristics, and performance advantages of four major composite types. These include magnetic MIPs for rapid separation, molecularly imprinted membranes for high-flux continuous separation, molecularly imprinted hydrogels with excellent biocompatibility, and porous MIPs based on metal-organic frameworks, covalent organic frameworks, and porous aromatic frameworks, which provide a high loading capacity. Furthermore, the application progress of these composites is reviewed in detail, specifically covering the selective separation and enrichment of flavonoids, alkaloids, polyphenols, polysaccharides, and terpenoids from complex herbal matrices. Furthermore, key problems in current research are deeply analyzed, like template residue leakage affecting food safety, and insufficient stability under extreme pH or temperature conditions. Finally, future development directions are envisioned, focusing on material optimization and the rational design of polymers using computational modeling. This review is expected to provide a reference for the in-depth research and application development of natural active ingredient separation.

Key words: molecularly imprinted composites, natural active ingredients, separation and enrichment