The Buzhongyiqi decoction (BD), a Chinese herbal medicine compound, have been used to treat myasthenia gravis (MG) and Alzheimer’s disease (AD). Both diseases are associated with acetylcholinesterase (AChE). We hypothesized that the bioactives were AChE inhibitors. To validate the hypothesis, a chemical structure database containing a total of 1,198 chemical structures were built from literature for the herbs (classified into Jun, Chen, Zuo, and Shi herbs, meaning sovereign, minister, assistant, and courier herbs) in BD. With ligand based and structure-based data mining technologies and molecular dynamic simulations, we found that the bioactives of the Buzhongyiqi decoction mainly existed within the Jun and Shi herbs. These bioactive were flavonoid derivatives that act as AChE inhibitors. The molecules of the Chen and Zuo herbs within the Buzhongyiqi decoction may have different functions, and need further investigation. Twenty-four phenylbenzofuran-like compounds were acquired based upon the data mining results, and tested with Ellman assays. We discovered five new AChE inhibitors with novel scaffolds with IC50 values ranging between 2.3 and 11 mM. Our work demonstrated that the bioactives of natural products could be identified by data mining technologies, and novel AChE inhibitors could be discovered by learning from the Nature.

Identifying ache inhibitors as bioactives from Chinese herbal medicine

251st National Meeting (2016)

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