Identification of novel bioactive constituents from traditional decoction of jiao-tai-Wan based on "co-decoction reaction" and comparative analysis with formula granules.

OBJECTIVE

The therapeutic equivalence between formula granules and traditional co-decoction remains a major clinical controversy. This study aims to investigate the scientific basis for the equivalence between formula granules and herbal piece decoctions using Jiao-Tai-Wan in the diabetic mouse model.

METHODS

This study employs Jiao-Tai-Wan using db/db diabetic mice as a disease model to investigate the scientific basis of equivalence between formula granules and herbal piece decoctions through multidimensional approaches. Using UPLC-QE- Orbitrap-MS, novel compounds generated during co-decoction were identified. Then, the hypoglycemic effects of formula granules, mixed individual decoctions, and combined decoction were systematically compared in db/db mice, complemented by 16S rRNA sequencing of gut microbiota and molecular docking of bioactive compounds with taste receptors.

RESULTS

Twenty-nine new co-decoction-related compounds were detected. All Jiao-Tai-Wan groups exhibited a more pronounced reduction in fasting blood glucose compared to the metformin group(p < 0.05), with efficacy descending as follows: co-decoction > mixed decoction > formula granules. Each preparation distinctly modulated gut microbiota. Strong binding (≤ -5.0 kcal/mol) was confirmed between main constituents (e.g., berberine, cinnamic acid) and receptors (TAS2R46, TRPV1).

CONCLUSIONS

This study identified novel compounds generated during the co- decoction of Jiao-Tai-Wan through UPLC-QE-Orbitrap-MS. Using a multi- dimensional approach encompassing efficacy comparison, gut microbiota modulation, and molecular docking, it preliminarily elucidated that these co-decoction reaction products may constitute the material basis and potential mechanism underlying the efficacy differences between formula granules and traditional combined decoctions. These findings offer important mechanistic insights into co-decoction reaction and validate potential clinical applications of granule formulations.