Iron deficiency anemia is a globally prevalent micronutrient deficiency disorder. Conventional inorganic and low-molecular-weight organic iron supplements are absorbed via the specific active transport pathway mediated by divalent metal transporter 1 (DMT1). This pathway has inherent drawbacks: strong dependence on intestinal microenvironment, susceptibility to interference from dietary antagonists, low iron bioavailability, and high risk of gastrointestinal oxidative damage. The Auricularia auricula polysaccharide‑iron complex (designated Auricul-F®) is a core-shell macromolecular colloidal complex that is coordinately synthesized by chelating ferric ions with natural polysaccharides extracted from Auricularia auricula. It possesses excellent gastrointestinal stability, water solubility and biocompatibility. In vitro cellular experiments, simulated gastrointestinal digestion models and in vivo animal metabolic studies have confirmed that Auricul-F® breaks the single ion transport mode of traditional iron agents. It achieves complete macromolecular internalization through clathrin-independent fluid-phase pinocytosis in intestinal epithelial cells, forming a dual absorption pathway dominated by pinocytosis and supplemented by DMT1-mediated transport. The core pinocytotic absorption process is not inhibited by intestinal pH fluctuations, phytic acid or competing metal ions. Meanwhile, vesicles inside cells can realize controlled slow release of iron ions, which greatly reduces gastrointestinal irritation and significantly improves iron bioavailability. This paper systematically elaborates the spatial structural characteristics, gastrointestinal homeostasis mechanism, hierarchical molecular cascade of pinocytotic absorption, key regulatory signaling proteins, intracellular iron metabolic reprogramming and vesicle recycling mechanism of Auricul-F®. A comparative analysis of core differences between the pinocytotic pathway and the classical DMT1 transport pathway is carried out to clarify the molecular essence of Auricul-F® for efficient and safe iron supplementation. This study aims to improve the theoretical system of intestinal absorption of natural fungal polysaccharide‑iron complexes, and provide solid theoretical and data support for its industrial application in functional fortified foods, foods for special medical purposes and novel iron-supplement formulations.

Nurfarih Hanna, Mohd Zarif Fikri Bin Mohd, Muhammad Nabil Fikri Bin Mohd, Nurfarazuna Binti Mohd Fadrol. Molecular Mechanism Underlying Intestinal Epithelial Cell Pinocytosis-Mediated Absorption of Auricularia auricula Polysaccharide-Iron Complex. Academic Journal of Agriculture & Life Sciences (2026), Vol. 7, Issue 1: 41-47. https://doi.org/10.25236/AJALS.2026.070107.

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