Secoisolariciresinol diglucoside (SDG) is the major lignan in wholegrain flaxseed.
However, extraction methods are complex and are associated with low yield and high
costs. Using a novel synthetic pathway, our group succeeded in chemically synthesizing
SDG (S,S and R,R enantiomers), which faithfully recapitulates the properties of their
natural counterparts, possessing strong antioxidant and free radical scavenging properties.
This study further extends initial findings by now investigating the DNA-radioprotective
properties of the synthetic SDG enantiomers compared to the commercial SDG. DNA radioprotection
was assessed by cell-free systems such as: (a) plasmid relaxation assay to determine
the extent of the supercoiled (SC) converted to open-circular (OC) plasmid DNA (pBR322)
after exposure of the plasmid to gamma radiation; and (b) determining the extent of
genomic DNA fragmentation. Exposure of plasmid DNA to 25 Gy of γ radiation resulted
in decreased supercoiled form and increased open-circular form, indicating radiation-induced
DNA damage. Synthetic SDG (S,S) and SDG (R,R), and commercial SDG at concentrations
of 25-250 μM significantly and equipotently reduced the radiation-induced supercoiled
to open-circular plasmid DNA in a dose-dependent conversion. In addition, exposure
of calf thymus DNA to 50 Gy of gamma radiation resulted in DNA fragments of low-molecular
weight (<6,000 bps), which was prevented in a dose-dependence manner by all synthetic
and natural SDG enantomers, at concentrations as low as 0.5 μM. These novel results
demonstrated that synthetic SDG (S,S) and SDG (R,R) isomers and commercial SDG possess
DNA-radioprotective properties. Such properties along with their antioxidant and free
radical scavenging activity, reported earlier, suggest that SDGs are promising candidates
for radioprotection for normal tissue damage as a result of accidental exposure during
radiation therapy for cancer treatment.