Unveiling the Molecular Mechanisms of Natural Triterpenoids From Mushrooms Against Type 2 Diabetes: A Critical Review

The exploration of triterpenoids derived from medicinal mushrooms presents an emerging frontier in managing type 2 diabetes (T2D). Triterpenoids achieve their therapeutic potential by targeting multiple pathways implicated in T2D pathology, including insulin resistance, chronic inflammation, and oxidative stress. This review critically summarizes the mechanisms by which mushroom-derived triterpenoids, such as ganoderic acid, betulinic acid, and pachymic acid, exert anti-diabetic effects. The molecular mechanisms of triterpenoids derived from medicinal mushrooms include the activation of AMP-activated protein kinase (AMPK) and phosphatidylinositol 3kinase (PI3K-Akt) signaling pathways, enhancing insulin sensitivity and glucose uptake, as well as the inhibition of α-glucosidase activity, thereby reducing postprandial hyperglycemia. Additionally, triterpenoids can alleviate insulin resistance and pancreatic β-cell dysfunction through modulating oxidative stress and inflammation. Notably, triterpenoids influence gut microbiota composition, promoting a healthier microbial balance that supports glucose metabolism and overall metabolic health. While preclinical studies underscore the promising potential of triterpenoids in T2D intervention, further high-quality clinical trials are needed to validate the mushroom-derived triterpenoids' clinical efficacy firmly. This review synthesizes these findings to establish a comprehensive framework for further research and product development of medical mushrooms.