Insights Into the Biological Mechanisms and Multifunctional Health Benefits of Morelloflavone

Morelloflavone (MF), a biflavonoid primarily found in Garcinia species, exhibits a wide range of health benefits, including antioxidative, anti‐inflammatory, anticancer, anti‐obesity, antidiabetic, antimicrobial, anti‐atherosclerotic, and neuroprotective effects. MF in exerting these bioactivities is closely linked to the modulation of critical molecular targets. This review provides a comprehensive and current examination of MF sources, physicochemical properties, biosynthesis and synthesis, bioactivities, particularly in cancer and inflammation, safety and toxicological effects of MF, and their underlying molecular mechanisms. In addition to Clusiaceae, MF can also be obtained from Tamaricaceae and Anacardiaceae. MF offers multiple health benefits, including anticancer, anti‐inflammatory, antioxidant, antiatherosclerotic, anti‐obesity, antidiabetic, anti‐metabolic syndrome, antimicrobial, and neuroprotective effects. These benefits stem from its impact on various regulatory mechanisms, including key proteins/enzymes, lipid and glucose metabolism, insulin signaling, ERK signaling, oxidative stress, and regulation of gut microbiota. Moreover, the multi‐target nature of MF makes it well‐suited for integration with big data and machine learning approaches to identify molecular signatures, predict ligand‐target interactions, and prioritize therapeutic pathways. Notably, preliminary clinical trials of MF‐containing formulations suggest therapeutic potential, though rigorous clinical trials of pure MF are still needed. Overall, MF shows promise for preventing certain chronic human diseases.