Lentinan, β-glucan from Shiitake (Lentinula edodes): A review on structure, conformational transition, and gastro-intestinal interaction contributing towards its anti-diabetic potential

Lentinan (LNT), a β-glucan in Shiitake mushroom (Lentinula edodes) has attracted attention for its potent biofunctionalities and immune-boosting properties. Despite comprehensive research into its chemical structure and conformation transitions, the exact mechanism of digestion and absorption remains a subject of exploration, especially its potential hypoglycemic effects. The conformation-dependent functionality of LNT in relation to hypoglycemic effects has yielded inconclusive results and health benefits. With an increasing number of individuals affected by type II diabetes mellitus (T2DM), elucidating the mechanism to unlock its nutraceutical potential is crucial. LNT's therapeutic potential as an antidiabetic drug lies in its ability to limit hyperglycemic effects. The review compiles fragmented information on LNT's configuration, structural characteristics, interactions in the gastrointestinal tract, and bioavailability with the aim of bridging the gap between in vivo and in vitro studies. Additionally, examining the bioavailability of LNT and addressing associated issues will encourage greater acceptance of Shiitake as a functional food supplement. This up-to-the-minute review provides a comprehensive overview of LNT's structural characteristics with respect to hypoglycemia in the gastrointestinal tract (GIT) modulating the glucose milieu. Additionally, it outlines the possible anti-diabetic mechanisms like regulation of carbohydrate digestion and absorption, hepatic oxidative stress, lipotoxicity, insulin sensitivity, advanced glycation end products (AGE) formation, redox stress, short-chain fatty acid (SCFA) formation, and gut-brain axis-induced satiety. This review presents these insights for the first time providing a foundation for unraveling LNT's mechanism, standardizing bioactivity assessment, and emphasizing the need for clinical trials to validate its potential as a superfood in diabetes management.