Next Article in Journal
The Ovarian Transcriptome of Reproductively Aged Multiparous Mice: Candidate Genes for Ovarian Cancer Protection
Next Article in Special Issue
A Critical Regulation of Th17 Cell Responses and Autoimmune Neuro-Inflammation by Ginsenoside Rg3
Previous Article in Journal
TLR2 and TLR4 Surface and Gene Expression in White Blood Cells after Fasting and Oral Glucose, Lipid and Protein Challenges: Influence of Obesity and Sex Hormones
Previous Article in Special Issue
Panax ginseng Pharmacopuncture: Current Status of the Research and Future Challenges
Open AccessArticle

Molecular Insight into Stereoselective ADME Characteristics of C20-24 Epimeric Epoxides of Protopanaxadiol by Docking Analysis

1
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264000, China
2
School of Chemistry and Chemical Engineering, Yantai University, Yantai 264000, China
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 112; https://doi.org/10.3390/biom10010112
Received: 6 December 2019 / Revised: 30 December 2019 / Accepted: 1 January 2020 / Published: 9 January 2020
(This article belongs to the Special Issue Advances in Ginsenosides)
Chirality is a common phenomenon, and it is meaningful to explore interactions between stereoselective bio-macromolecules and chiral small molecules with preclinical and clinical significance. Protopanaxadiol-type ginsenosides are main effective ingredients in ginseng and are prone to biotransformation into a pair of ocotillol C20-24 epoxide epimers, namely, (20S,24S)-epoxy-dammarane-3,12,25-triol (24S-PDQ) and (20S,24R)-epoxy dammarane-3,12,25-triol (24R-PDQ) that display stereoselective fate in vivo. However, possible molecular mechanisms involved are still unclear. The present study aimed to investigate stereoselective ADME (absorption, distribution, metabolism and excretion) characteristics of PDQ epimers based on molecular docking analysis of their interaction with some vital proteins responsible for drug disposal. Homology modeling was performed to obtain 3D-structure of the human isoenzyme UGT1A8, while calculation of docking score and binding free energy and ligand–protein interaction pattern analysis were achieved by using the Schrödinger package. Stereoselective interaction was found for both UGT1A8 and CYP3A4, demonstrating that 24S-PDQ was more susceptible to glucuronidation, whereas 24R-PDQ was more prone to oxidation catalyzed by CYP3A4. However, both epimers displayed similarly strong interaction with P-gp, a protein with energy-dependent drug-pump function, suggesting an effect of the dammarane skeleton but not C-24 stereo-configuration. These findings provide an insight into stereo-selectivity of ginsenosides, as well as a support the rational development of ginseng products. View Full-Text
Keywords: ocotillol type ginsenoside epimers; stereoselective ADME characteristics; molecular docking analysis; homology modeling; molecular interaction ocotillol type ginsenoside epimers; stereoselective ADME characteristics; molecular docking analysis; homology modeling; molecular interaction
Show Figures

Graphical abstract

MDPI and ACS Style

Guo, W.; Li, Z.; Yuan, M.; Chen, G.; Li, Q.; Xu, H.; Yang, X. Molecular Insight into Stereoselective ADME Characteristics of C20-24 Epimeric Epoxides of Protopanaxadiol by Docking Analysis. Biomolecules 2020, 10, 112.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop