LC-MS-based 3 M profiling strategy and network pharmacology reveal ginsenoside diversity and bioactivity transformation during decoction of the Shengmai formula.

Shengmai formula decoction (SMD) has beneficial pharmacological effects in inflammatory and metabolic diseases. Ginsenosides are important contributors to the pharmacological effects of SMD. However, the differences in the ginsenoside profile before and after compatibility decoction and the underlying interaction transformation were unclear, which restricted the rational usage and product development of SMD. A 3 M profiling strategy (Mass defect filtering (MDF), molecular networking and metabolomics) based on UPLC-Q-TOF-MS/MS was employed to characterize ginsenosides in Panax ginseng C.A.Mey (PG) and SMD while identifying differences. Network pharmacology was subsequently utilized to evaluate their bioactivity changes. As a result, a total of 155 ginsenosides were identified via the above method; 136 were detected in PG, and 95 were detected in SMD. 36 different ginsenosides were found based on metabonomics, 13 were more abundant in SMD than in PG, primarily consisting of rare ginsenosides with fewer sugar linkages, including Rh1, Rg2, Rg3, Ro, Rs3, Rk1, Rg5, Rs4, Rs5, and others. The contents of 23 ginsenosides decreased, primarily consisting of macro ginsenosides with more attached sugar groups, including Rg1, Re, Rf, Rb1, Rc, Rb2, Rd, Rs1, Rs2, and others. Disassembled prescription revealed that the coexistence of Schisandra chinensis (Turcz.) Baill. (SC) accelerated ginsenoside transformation due to its strong acidity. Network pharmacology analysis revealed that ginsenosides produced in SMD significantly enhance anti-cancer and anti-inflammatory effects. This study successfully analyzed the diversity and bioactivity changes of ginsenosides in SMD, providing a scientific foundation for optimizing its preparation and therapeutic applications.