1-Deoxynojirimycin: a comprehensive review of sources, biosynthesis pathways, strategies to enhance its production, and anti-diabetic activities

Diabetes mellitus (DM) is a common health problem characterized by inadequate control of blood glucose levels. It is associated with severe clinical complications such as diabetic nephropathy, cardiomyopathy, neuropathy, and retinopathy. The prevalence of DM and its complications has significantly increased worldwide, and existing drugs have some undesirable side effects. 1-Deoxynojirimycin (1-dnj) is an iminosugar naturally present in mulberry and dayflower plants, as well as in several bacterial strains, and exerts a broad spectrum of biological activities. 1-dnj has been reported to possess strong potential for combating DM and its complications. In this review, we summarized the literature regarding the sources, biosynthesis pathways, strategies to enhance production, and anti-diabetic activities and mechanisms of 1-dnj. Glucose and lysine are two precursors of 1-dnj biosynthesis in plants and microbes; however, the precise biosynthesis pathways have not yet been fully clarified. The enhancement of 1-dnj content in plants and microbes can be achieved using physical techniques, microbial mutagenesis, fermentation, and genetic engineering approaches. 1-dnj ameliorates DM by improving insulin resistance, promoting glucose and lipid metabolism, improving β-cell function, enhancing anti-inflammatory and antioxidant activities, and reversing gut microbiota dysbiosis. 1-dnj also regulates various signaling pathways in the heart, kidneys, liver, pancreas, skeletal muscle, and other organs by acting on different molecular targets, alleviating DM. In conclusion, 1-dnj shows strong potential for combating DM. However, further mechanistic studies are necessary to elucidate the biosynthesis pathways, validate the health benefits of 1-dnj, and refine methods for its enrichment.