Triptolide and methotrexate binding competitively to bovine serum albumin: A study of spectroscopic experiments, molecular docking, and molecular dynamic simulation

The potential drug-drug interaction is essential to monitor for the combination therapy of Tripterygium wilfordii Hook F and methotrexate in rheumatoid arthritis, a Chinese clinical approach. The purpose was to investigate the binding mechanisms of triptolide, the active ingredient extracted from Tripterygium wilfordii Hook F, and methotrexate with BSA, individually and in combination, using multi-spectroscopic experiments, molecular docking, and molecular dynamic simulation. Fluorescence studies indicated that triptolide/methotrexate interacted with BSA at Site I through the static quenching mechanism and synchronous fluorescence, 3D fluorescence, and UV–vis absorption spectra obtained results for changes in micro-environmental polarity around amino acid residues. For the ternary system, methotrexate was replaced from the binding site as triptolide had a higher affinity for BSA, which possibly can result in an increased plasma drug concentration of methotrexate. Besides, CD studies implied that α-helix content of BSA decreased more when reacted with triptolide than methotrexate. Further, molecular docking and molecular dynamic simulation demonstrated that BSA-triptolide had lower binding energy compared with BSA-methotrexate due to the van der Waals forces, hydrogen bonds, and hydrophobic interactions. This study provided information about the safety of triptolide and methotrexate for synergistic clinical treatment of rheumatoid arthritis.