Schisandra chinensis peptidoglycan-assisted transmembrane transport of lignans uniquely altered the pharmacokinetic and pharmacodynamic mechanisms in human HepG2 cell model

Charng-Cherng Chyau; Yaw-Bee Ker; Chi-Huang Chang; Shiau-Huei Huang; Hui-Er Wang; Chiung-Chi Peng; Robert Y Peng

doi:10.1371/journal.pone.0085165

Schisandra chinensis peptidoglycan-assisted transmembrane transport of lignans uniquely altered the pharmacokinetic and pharmacodynamic mechanisms in human HepG2 cell model

PLoS One. 2014 Jan 27;9(1):e85165. doi: 10.1371/journal.pone.0085165. eCollection 2014.

Authors

Charng-Cherng Chyau¹, Yaw-Bee Ker², Chi-Huang Chang¹, Shiau-Huei Huang¹, Hui-Er Wang², Chiung-Chi Peng³, Robert Y Peng⁴

Affiliations

¹ Research Institute of Biotechnology, Hungkuang University, Shalu County, Taichung City, Taiwan.
² Department of Food And Applied Technology, Hungkuang University, Shalu County, Taichung City, Taiwan.
³ Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ Research Institute of Biotechnology, Hungkuang University, Shalu County, Taichung City, Taiwan ; Research Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.

Abstract

Schisandra chinensis (Turz Baill) (S. chinensis) (SC) fruit is a hepatoprotective herb containing many lignans and a large amount of polysaccharides. A novel polysaccharide (called SC-2) was isolated from SC of MW 841 kDa, which exhibited a protein-to-polysaccharide ratio of 0.4089, and showed a characteristic FTIR spectrum of a peptidoglycan. Powder X-ray diffraction revealed microcrystalline structures within SC-2. SC-2 contained 10 monosaccharides and 15 amino acids (essential amino acids of 78.12%w/w). In a HepG2 cell model, SC-2 was shown by MTT and TUNEL assay to be completely non-cytotoxic. A kinetic analysis and fluorescence-labeling technique revealed no intracellular disposition of SC-2. Combined treatment of lignans with SC-2 enhanced the intracellular transport of schisandrin B and deoxyschisandrin but decreased that of gomisin C, resulting in alteration of cell-killing bioactivity. The Second Law of Thermodynamics allows this type of unidirectional transport. Conclusively, SC-2 alters the transport and cell killing capability by a "Catcher-Pitcher Unidirectional Transport Mechanism".

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Biological Transport / drug effects
Biological Transport / physiology
Fruit / chemistry*
Hep G2 Cells
Humans
In Situ Nick-End Labeling
Lignans / metabolism*
Membrane Transport Modulators / pharmacology*
Peptidoglycan / analysis
Peptidoglycan / pharmacology*
Plant Extracts / analysis
Plant Extracts / pharmacology*
Schisandra / chemistry*
Spectroscopy, Fourier Transform Infrared
Tetrazolium Salts
Thiazoles
X-Ray Diffraction

Substances

Lignans
Membrane Transport Modulators
Peptidoglycan
Plant Extracts
Tetrazolium Salts
Thiazoles
thiazolyl blue

Grants and funding

This study was supported by grants from the National Science Council of Taiwan (NSC-97-2313-B-241-002-MY3 and NSC-100-2313-B-241-004). Additional support was received from Taipei Medical University (TMU101-AE1-B11 and TMU102-SHH-11). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.