Identification of novel bioactive constituents from traditional decoction of jiao-tai-Wan based on "co-decoction
Ping Sun1, Shuang Li2, Jinyan Teng3
1Department of Endocrinology, Postgraduate Union training base of Xiangyang No.1 People's Hospital, School of Medicine, Wuhan University of Science and Technology, Xiangyang 441000, Hubei, China.
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.


