We have been working on improving ginsenosides bioavailability over several rounds of iGEM since we joined the competiton in 2011. This year's focus is to comply with NO-RELEASE policy of iGEM community.
We achieved our goal by applying a chemical reaction to hydrolyze ginsenosides and improved their bioavailability without compromising therapeutic values. Using mathematical models and published animal experiment data, we argued that our current approach would be safe and more efficacious than the common practice of ginsenosides usage methods.
The effective constituents of ginseng are glycosides and saponins. A set of data for the modeling of ginsenosideRb1, ginsenoside Rg1 and NotoginsenosideR1 referred to paper about Fufang Xueshuangtong.[1]
Three chemical compounds:
We use JDesigner (a visual biochemical network simulation tool) for the modeling below.
It can be seen from the structure that the three active ingredients can be converted by the loss or increase of free radicals, so we boldly assume a local circulation model to simulate the absorption of drugs into organisms.
Modeling for absorbing:
Curve of modeling:
The trend of the curve is similar to the experiment data.The following is the absorption of three saponins into the human body respectively.
Concentration in plasma of notoginsenosideR1: a:Simulating by JDesigner b:Experiment data
Concentration in plasma of GinsenosideRg1 a:Simulating by JDesigner b:Experiment data
Concentration in plasma of GinsenosideRb1 a:Simulating by JDesigner b:Experiment data
Following the NO-RELEASE principle, if ginseng or drugs are fed directly to the organisms, it can be seen that the detection of active ingredients cannot be determined whether absorbed by the organisms, but also produce other unnecessary ingredients absorbed, which is wasteful, and can not be determined whether it is harmful to the organisms. But according to our hypothesis, direct feeding of active ingredients, firstly, can be directly detected whether absorbed and secondly, there are no excess ingredients into the organisms. This follows the NO-RELEASE principle.
Through an in-depth analysis of the experimental data by mathematical models, it is inferred that ginsenosides are converted several times after notification of oral absorption before deglycosylated saponins and glycosylated saponins. Saponins and saponins produced by our chemical hydrolysis method can significantly improve oral bioavailability due to their weakened structural polarity and enhanced lipid solubility. After the components enter the body through repeated glycosylation-deglycosylation cycle metabolism, can produce a variety of bioactive substances, to ensure the original efficacy of ginsenosides, will not increase adverse reactions.
