Multi-spectroscopic and molecular modeling studies on the interactions of serum albumin with 20(S, R)-protopanaxadiol and 20(S, R)-protopanaxatriol that inhibit HCT-116 cells proliferation

Serum albumin (SA) acts as the carrier protein to transport drugs and plays a crucial role in the pharmacokinetics of distribution. In this work, the cytotoxicities of 20(S, R)-protopanaxadiol [20(S, R)-PPD] and 20(S, R)-proto-panaxatriol [20(S, R)-PPT] against HCT-116 cell lines were assessed. 20(S)-PPD, 20(R)-PPD, 20(S)-PPT, and 20 (R)-PPT inhibited the cells growth in a concentration-dependent manner with the IC50 values of 30.27, 18.80, 68.28, and 14.38 mu M, respectively. The result of ABTS assay showed that 20(S, R)-PPD-BSA exhibited a higher antioxidant activity than that of 20(S, R)-PPD alone. Subsequently, the binding affinity and interaction mech-anism of ginsenosides with SA were studied by the ultraviolet-visible absorption and fluorescence spectroscopy, which indicated that ginsenosides interfered with the microenvironment around amide bonds in SA. Through the calculation of Stern-Volmer plot, the quenching rate k(q) values of 20(S)-PPD, 20(R)-PPD, 20(S)-PPT, and 20(R)-PPT were 6.75, 4.30, 2.37, and 3.31 (c 10(11) M-1 s(-1)), respectively. These results suggested that the quenching was not caused by dynamic collision, but the formation of ginsenoside-SA complexes. The results of molecular docking suggested that these compounds tended to bind more strongly to Sudlow's site II of HSA rather than Sudlow's site I. In addition, 20(S)-ginsenosides showed more stable binding to HSA in comparison with 20(R)-ginsenosides, which may help elucidating the mechanisms that account for the stronger bioactivities of 20(S)-ginsenosides.

Automated summary

The study demonstrated the cytotoxicity of 20(S, R)-protopanaxadiol and 20(S, R)-protopanaxatriol on HCT-116 cell lines, with 20(S, R)-PPD-BSA showing higher antioxidant activity than 20(S, R)-PPD alone. Ginsenosides were found to interfere with the microenvironment of SA and form complexes, indicating the stronger bioactivities of 20(S)-ginsenosides binding to HSA compared to 20(R)-ginsenosides.