A Novel Edible Eutectogel Containing Baicalein and 1-Deoxynojirimycin Alleviates Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM), one of the most rapidly growing metabolic disorders globally, poses a substantial public health burden. In this study, a novel edible eutectogel was innovatively developed for the co-delivery of natural active ingredients, baicalein (Bai), and 1-deoxynojirimycin (DNJ). Utilizing a deep eutectic solvent (DES) system, the hydrophobic Bai and hydrophilic DNJ were co-dissolved and encapsulated within the eutectogel (Bai-DNJ/EG), enabling gastric protection and targeted intestinal release. Animal experimental demonstrated that the Bai-DNJ/EG significantly ameliorated multiple pathological features, including blood glucose reduction, improved insulin sensitivity, attenuated systemic inflammation, decreased fat accumulation, and mitigated organ damage. Compared with Bai/EG and DNJ/EG, Bai-DNJ/EG exhibited superior therapeutic efficacy across all parameters, indicating a synergistic effect between the Bai and DNJ. The dose of Bai in Bai-DNJ/EG was reduced by 50% relative to previous studies, and DNJ was 7.5 times less than that of clinical use in a Chinese herbal preparation for lowering blood glucose. In addition, comparison of lipid metabolism and inflammatory factors between Bai HG and Bai/EG groups indicated that DES enhanced the pharmacological activity of Bai by improving its solubility. Furthermore, 16S rRNA sequencing revealed that Bai-DNJ/EG positively regulates gut microbiota homeostasis and repairs the intestinal barrier. Bai-DNJ/EG inhibited deleterious bacteria including Methanobacteriaceae, Pseudomonadota, Campylobacterota, and Spirochaetota, while promoted the SCFA-producing bacteria, for example, Muribaculaceae and Butyricicoccaceae. This study presents a groundbreaking strategy for the synergistic delivery of natural bioactives and establishes a new paradigm for modernized traditional natural medicine formulations.