Dihydroquercetin in Obesity and Prediabetes: Case Report and Insights from Molecular Modeling.

Dihydroquercetin (DHQ) is a promising object for the development of a treatment for patients with obesity and prediabetes requiring a moderate therapeutic effect. This paper reports a clinical case of DHQ application in a 30-year-old Caucasian male and proposes a molecular mechanism of its anti-obesity effect. DHQ was administrated as a dietary supplement at a dose of 100-200 mg/day during 3 months with treatment interruption for 1 month. The data collected one month before the treatment were used as a control. The molecular aspects were studied via molecular docking with β3-adrenoceptor (ADRB3, PDB ID: 9IJE) and peroxisome proliferator-activated receptor γ (PPARG, PDB ID: 2ZNO) and molecular dynamic simulation under conditions mimicking a human cellular environment. A pronounced weight decrease up to 0.73 kg/week was observed during DHQ administration. The highest affinity to ADRB3 was observed for the non-ionized H2aH3e-conformation of 2S,3R-DHQ (-8.846 kcal/mol). Molecules with 2S-configuration demonstrate 0.332 kcal/mol higher affinity to PPARG compared to 2R-stereoisomers. The intermolecular complex with cis-DHQ demonstrated higher stability in molecular dynamics simulation. The insights gained from this study may contribute to our understanding of flavonoids not merely as antioxidants but also as active ingredients that selectively interact with receptors. If future investigations confirm these results, they may serve as a foundation for developing a new class of anti-obesity remedies that act via ADRB3.