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Multi-dimensional PK-PD insights into Lianhua Qingwen's formula compatibility
Hui Qi1, Simian Chen2, Xueqin Chen3
1State Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, Hebei, China; Hebei Luoxue Innovation Medical Research Institute, Shijiazhuang, 050091, Hebei, China; Affiliated Yiling Hospital of Hebei Medical University, Shijiazhuang, 050091, Hebei, China.
Ethnopharmacological Relevance:
Lianhua Qingwen (LHQW), a traditional Chinese medicine, combines three classical formulas-Maxing Shigan decoction (MXSGD), Yinqiao powder (YQP), and Rhei Radix et Rhizoma (Dahuang)-demonstrating adaptive optimization of classical prescriptions. Despite its well-documented pharmacological effects, the scientific rationale for its compatibility remains underexplored.
Aim Of The Study:
To elucidate the functional roles and synergistic mechanisms of LHQW through a formula-disassembled strategy combined pharmacodynamic (PD) and pharmacokinetic (PK) analysis.
Materials And Methods:
LHQW's components were identified using UPLC-HRMS. Three disassembled prescriptions (DPs): LHQW-M (excluding MXSGD-related herbs), LHQW-Y (excluding YQP-related herbs), and LHQW-D (excluding Dahuang) were created based on LHQW's compatibility theory. Multidimensional PD models were established to assess antiviral, anti-inflammatory, gut-lung axis regulation, antitussive, and antipyretic effects. Systemic exposure of key components in rat plasma was quantified using HPLC-MS/MS, followed by PK-PD integrated analysis.
Results:
The botanical origins of 211 compounds identified in LHQW were clarified. PD evaluations revealed that YQP-derived components drove antiviral and anti-mucus effects, MXSGD mediated antitussive and antipyretic actions, and Dahuang enhanced gut-lung axis protection. Synergistic anti-inflammatory effects emerged from multi-components. PK analysis showed higher systemic exposure of certain components in LHQW than its DPs, correlating with PD efficacy.
Conclusions:
Using an integrated formula-disassembled strategy and PK-PD analysis, we systematically deciphered LHQW's compatibility principle: YQP, MXSGD, and Dahuang exert distinct therapeutic effects and synergistic mechanisms; intact LHQW's optimized component exposure underpins its holistic efficacy. These findings provide mechanistic evidence for LHQW's formula design, highlighting the scientific intelligence of integrating classical and modern medical principles.
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