Dihydromyricetin as a Dietary Supplement Enhances Hypoglycemic Efficacy: Synergistic Modulation of the Gut-Liver with Sangzhi Alkaloids

Chronic hyperglycemia, a hallmark of Type 2 diabetes mellitus, presents significant challenges in long-term management due to drug resistance and adverse effects. Dihydromyricetin (DHM), a natural flavanol from vine tea ( Ampelopsis grossedentata ), widely recognized as a nutraceutical, shows potential in enhancing the efficacy of pharmacological therapies. This study investigates the role of DHM in improving the hypoglycemic effects of Sangzhi Alkaloids (SZ-A), a commercially used glucosidase inhibitor. Our results demonstrate that DHM supplementation allows for a reduction in SZ-A dosage while maintaining or surpassing its glucose-lowering efficacy, thereby mitigating gastrointestinal side effects. Mechanistic studies reveal that this combination modulates the gut-liver axis, reducing ER stress, and enhancing gut microbiota diversity, including increased beneficial bacteria and non-12OH bile acids. These findings highlight DHM’s potential as an effective adjunctive nutraceutical, offering a safer and more efficient therapeutic strategy for managing hyperglycemia and related metabolic disorders.