From chemical to mechanism-driven quality control of <i>Glehniae Radix</i>: spectrum effect – chemometrics–pharmacology integration decoding antioxidant–anti-inflammatory crosstalk

<i>Glehniae Radix</i> (GR) is primarily produced in Laiyang and Chifeng. It is a functional food with therapeutic and health-promoting effects due to its antioxidant and anti-inflammatory properties. However, the current standards only stipulate authentication criteria, without establishing a comprehensive evaluation framework to systematically enhance the quality control of GR. This study aimed to establish a "chemical-mechanism" quality control framework for GR through a three-tiered strategy: "chemical composition analysis-bioactivity quantification-mechanism network validation." Initially, UPLC fingerprints of 14 GR batches were constructed, and their antioxidant and anti-inflammatory activities were evaluated. Multivariate statistical models combined with activity indices were employed to optimize spectrum-effect relationships using a random forest algorithm, predicting bioactive constituents. Network pharmacology, molecular docking, and dynamics simulations were integrated to elucidate multi-component, multi-target, and multi-pathway mechanisms. Chemometric analysis identified imperatorin as a marker for quantifying differences between Laiyang and Chifeng origins. Pharmacodynamic assays confirmed GR's antioxidant and anti-inflammatory efficacy. Random forest-optimized spectrum-effect modeling prioritized falcarindiol and panaxynol as bioactive markers. Network pharmacology predicted GR's regulation of EGFR tyrosine kinase inhibitor resistance and ErbB signaling <i>via</i> targets (EGFR, PTGS2, NFKB1). Molecular docking revealed strong binding affinity (<i>e.g.</i>, imperatorin-EGFR: -9.046 kcal mol^-1), and dynamics simulations confirmed complex stability. Thus, imperatorin, falcarindiol, and panaxynol were prioritized as quality markers. This study establishes a data-driven framework linking GR's chemical composition to antioxidant/anti-inflammatory mechanisms, advancing batch consistency control and precision applications in clinical disorders.