Analysis of the compatibility rules of Zhizi Baipi decoction:A multidimensional integrated study based on chemical profile-metabolic conversion-pharmacodynamics correlation.

Rheumatoid arthritis (RA), a refractory autoimmune disease, often leads to adverse reactions from long-term use of existing clinical drugs, resulting in insufficient satisfaction of patients' needs. Traditional Chinese Medicine (TCM) formulas have the advantage of overall regulation with multi-components and multi-targets. Zhizi Baipi Decoction (ZBD), a classic heat-clearing and dampness-draining formula, shows significant therapeutic efficacy against RA in clinical practice and is widely used as a foundational treatment. However, its pharmacological substance basis, metabolic processes, and compatibility mechanisms remain unclear, impeding its modernization. This study established a multidimensional strategy integrating "chemical profile- metabolic transformation-pharmacodynamic verification" to elucidate the active constituents and compatibility rules of ZBD. For the first time, the ZBD whole formula was comprehensively compared with its disassembled formula using UHPLC-Q-TOF/MS, serum pharmacochemistry, and a collagen-induced arthritis (CIA) rat model. In vitro, 147 chemical components were identified. Compared with the GPR formula, the whole formula presented 48 additional components and a decrease of 28 components In vivo, 28 prototype components and 70 metabolites were detected. Compared with the GPR formula, the whole formula exhibited 15 additional absorbed blood components and a decrease of 9 blood components. Pharmacological results demonstrated that the ZBD whole formula outperformed all disassembled groups in alleviating arthritis symptoms, suppressing synovial inflammation, and rebalancing pro-/anti-inflammatory cytokines in CIA rats. In summary, this research systematically revealed ZBD's pharmacological substance basis and compatibility rules from chemical, metabolic, and pharmacological effects. It clarified the scientific basis for ZBD's "monarch, minister, assistant, and envoy" synergy, "efficiency-enhancing" component regulation, and role in promoting metabolic transformation, providing a systematic strategy and experimental paradigm for the modernization research of TCM formulas.