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http://dx.doi.org/10.1016/j.jgr.2016.06.005

The interaction of serum albumin with ginsenoside Rh2 resulted in the downregulation of ginsenoside Rh2 cytotoxicity  

Lin, Yingjia (Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University)
Li, Yang (Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University)
Song, Zhi-Guang (College of Chemistry, Jilin University)
Zhu, Hongyan (Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University)
Jin, Ying-Hua (Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University)
Publication Information
Journal of Ginseng Research / v.41, no.3, 2017 , pp. 330-338 More about this Journal
Abstract
Background: Ginsenoside Rh2 (G-Rh2) is a ginseng saponin that is widely investigated because of its remarkable antitumor activity. However, the molecular mechanism by which (20S) G-Rh2 triggers its functions and how target animals avoid its cytotoxic action remains largely unknown. Methods: Phage display was used to screen the human targets of (20S) G-Rh2. Fluorescence spectroscopy and UV-visible absorption spectroscopy were used to confirm the interaction of candidate target proteins and (20S) G-Rh2. Molecular docking was utilized to calculate the estimated free energy of binding and to structurally visualize their interactions. MTT assay and immunoblotting were used to assess whether human serum albumin (HSA), bovine serum albumin (BSA), and bovine serum can reduce the cytotoxic activity of (20S) G-Rh2 in HepG2 cells. Results: In phage display, (20S) G-Rh2-beads and (20R) G-Rh2-beads were combined with numerous kinds of phages, and a total of 111 different human complementary DNAs (cDNA) were identified, including HSA which had the highest rate. The binding constant and number of binding site in the interaction between (20S)-Rh2 and HSA were $3.5{\times}10^5M^{-1}$ and 1, and those in the interaction between (20S) G-Rh2 and BSA were $1.4{\times}10^5M^{-1}$ and 1. The quenching mechanism is static quenching. HSA, BSA and bovine serum significantly reduced the proapoptotic effect of (20S) G-Rh2. Conclusion: HSA and BSA interact with (20S) G-Rh2. Serum inhibited the activity of (20S) G-Rh2 mainly due to the interaction between (20S) G-Rh2 and serum albumin (SA). This study proposes that HSA may enhance (20S) G-Rh2 water solubility, and thus might be used as nanoparticles in the (20S) G-Rh2 delivery process.
Keywords
cytotoxic effect; fluorescence spectroscopy; G-Rh2 human target; phage display; serum albumin;
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