The Therapeutic Potential of Berberine and Resveratrol in Type 2 Diabetes Treatment: Pharmacokinetic and Bioactivity Properties, and Molecular Docking Analysis

Type 2 diabetes (T2D), typically characterized by insulin resistance, is a metabolic disorder that occurs when the body cannot use insulin effectively or does not produce enough insulin. In the treatment of T2D, insulin, metformin, and sulfonylureas are commonly used. Given the limitations of current treatment options, there is a strong need for intensive efforts in the discovery of new drugs. Berberine exhibits antidiabetic effects and possesses anti-inflammatory and antioxidant properties. Resveratrol is another natural compound that has been extensively researched due to its antioxidant and anti-inflammatory characteristics. This study aimed to investigate the interactions between berberine and resveratrol with proteins related to or causing T2D, including ADIPOR1 (PDB-ID: 6ks1), ADIPOR2 (PDB-ID: 5lxg), TNF-α (PDB-ID: 7kpb), PTP1B (PDB-ID: 4i8n), GLUT1 (PDB-ID: 4pyp), IGF-IR (PDB-ID: 8eyr), IGF1 (PDB-ID: 6pyh), ADAMTS9 (PDB-ID: 3ppv), and SPHK2 (PDB ID: 4v24). SwissADME was used to assess the pharmacokinetic properties of berberine and resveratrol. Molecular docking was performed to analyze the interactions between these ligands and the specified proteins. Additionally, the potential bioactivity features of compounds were determined. Protein-protein interactions were obtained from the STRING database. The study data indicated that both compounds have high blood-brain barrier (BBB) penetration and gastrointestinal absorption ability (HIA). Besides, berberine exhibited the highest binding affinity with GLUT4 (-10.1 Kcal/mol), GLUT1 (-9.3 Kcal/mol), and SPHK2 (-9.3 Kcal/mol), while resveratrol showed strong binding with SPHK2 (-9.0 Kcal/mol) and TNF-α (-8.7 Kcal/mol) and. All proteins displayed binding energies of more than -7 Kcal/mol, suggesting that both berberine and resveratrol hold promise as potential drug candidates for T2D.