Schisandra chinensis peptidoglycan-assisted transmembrane transport of lignans uniquely altered the pharmacokinetic and pharmacodynamic mechanisms in human HepG2 cell model.
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".
Research Institute of Biotechnology, Hungkuang University, Shalu County, Taichung City, Taiwan.
Charng-Cherng
CC
Chyau
Department of Food And Applied Technology, Hungkuang University, Shalu County, Taichung City, Taiwan.
Yaw-Bee
YB
Ker
Research Institute of Biotechnology, Hungkuang University, Shalu County, Taichung City, Taiwan.
Chi-Huang
CH
Chang
Research Institute of Biotechnology, Hungkuang University, Shalu County, Taichung City, Taiwan.
Shiau-Huei
SH
Huang
Department of Food And Applied Technology, Hungkuang University, Shalu County, Taichung City, Taiwan.
Hui-Er
HE
Wang
Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
Chiung-Chi
CC
Peng
Research Institute of Biotechnology, Hungkuang University, Shalu County, Taichung City, Taiwan ; Research Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
Robert Y
RY
Peng
D000704:Analysis of Variance; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D005638:Fruit / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D017705:Lignans / Q000378:metabolism*; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D010457:Peptidoglycan / Q000032:analysis / Q000494:pharmacology*; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D032141:Schisandra / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013778:Tetrazolium Salts; D013844:Thiazoles; D014961:X-Ray Diffraction
D017705:Lignans; D049990:Membrane Transport Modulators; D010457:Peptidoglycan; D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue