Analysis of new therapeutic strategies for diabetes mellitus based on traditional Chinese medicine “xiaoke” formulae

To develop new therapeutic strategies for diabetes mellitus (DM) by analyzing the mechanisms of action of traditional Chinese medicine (TCM) “xiaoke” formulae (TCM prescriptions for remedying xiaoke).

We characterized 291 xiaoke formulae, including the herbs contained, chemical composition, constituents' targets, and corresponding genes. Xiaoke-related genes were retrieved based on the relationships of constituents' targets and xiaoke formulae, and a threshold of over 95.88% occurrence of each constituent target in the 291 TCM formulae served as a definition for xiaoke-related genes. Upon comparison with DM-related genes in the DisGeNET database, the genes differing in expression between cases administered TCM and synthetic drugs were explored using a TCM grammar system.

The results showed that xiaoke formulae and 14 exclusively xiaoke-related genes were significantly associated with multiple biological processes closely related to DM and diabetic complications (P < .01). Moreover, intervention in the expression of these xiaoke-related genes would affect DM-related genes directly or indirectly.

The 14 xiaoke-related genes APEX1, EHMT2, TSHR, CBX1, FEN1, GMNN, JUN, KMT2A, MAPT, POLI, USP1, PIN1, POLB, and POLK can serve as candidate genes for anti-diabetic drug design. Compared with DM-related genes in DisGeNET, intervention in the expression of 14 xiaoke-related genes by TCM formulae has the potential to not only lower blood glucose, but also reduce the occurrence of some side effects and inhibit the development of diabetic complications. These findings will contribute to the discovery of new strategies for treating DM.