Strategy of integrated evaluation on treatment of traditional Chinese medicine as ‘interaction of system to system’ and establishment of novel fuzzy target contribution recognition with herb-pairs, a case study on Astragali Radix-Fructus Corni

• A novel generally applicable strategy for pharmacology research system on diabetic nephropathy (DN).
• The strategy was inspired by an idea that we assumed TCM cured a disease as an “interaction of system to system”.
• Relative distance between each treated group and the DN group from PLS-DA score plot being calculated was introduced.
• A novel agent, CG6, was acquired on the treatment of DN by employing the proposed strategy.
• It is the first time to reveal the molecular mechanism of CG6 on the anti-DN via an NFE2L2 activation-dependent pathway.

To date, in the struggle against diseases and the development of TCM, what we lack is wisdom rather than knowledge. Studies on pharmacology of traditional Chinese medicine are facing critical challenges on how to select the proper parameters or targets to represent the pharmacological evaluation system. With seven steps of optimized modules established by ourselves, we can re-evaluate TCM in a panorama view with a proper pharmacological evaluation system. In this article, with the treatment of TCM as ‘interaction of system to system’, a novel and generally applicable approach called fuzzy target contribution recognition was established and agents from Astragali Radix-Fructus Corni in resisting diabetic nephropathy were successfully discovered for the first time. CG6, a promising agent from this herb-pair on the treatment of diabetic nephropathy, was finally acquired and its possible molecular mechanism was explored through a nuclear factor erythroid 2-Like 2 (NFE2L2) activation-dependent pathway.

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