An integrated quality evaluation strategy combining chemical fingerprinting, chemometrics, network pharmacology, and spectrum-effect relationship for optimizing the harvest time and post-harvest processing of Clematidis Radix et Rhizoma.

Clematidis Radix et Rhizoma (CRR) has a long history of medicinal use, yet the quality of its commercial products has increasingly deteriorated with the expansion of cultivation. Therefore, a comprehensive quality evaluation strategy was proposed to improve its quality control. In this study, 75 metabolites were identified in commercial CRR by UPLC-Q-TOF-MS, with triterpenoid saponins as the major constituents. Accordingly, a simple HPLC-DAD method using acetonitrile-0.05% phosphoric acid as the mobile phase and detection at 210 nm and 330 nm was developed to establish fingerprints of 19 batches of CRR from different origins and to quantify five characteristic components. Chemometric analysis combined with network pharmacology prediction and spectrum-effect relationship analysis identified Clematichinenoside AR, Clematomandshurica saponin B, and Clemomandshuricoside B as key anti-inflammatory constituents of CRR. The developed quality evaluation strategy was further applied to assess the optimal origin, production region, harvest time, and post-harvest processing conditions of CRR. Results showed that CRR derived from Clematis terniflora var. manshurica (Rupr.) Ohwi (CTMO) exhibited superior quality, primarily due to the higher levels of key anti-inflammatory saponins (Clematichinenoside AR, Clematomandshurica saponin B, and Clemomandshuricoside B), particularly those from northeastern China. Late August was identified as the optimal harvest time for CTMO, and three-year-old plants showed the highest quality. Among several processing methods, oven-drying was considered the most suitable method for large-scale production, with 60 °C as the optimal processing temperature. These findings provide a practical strategy for stabilizing and improving the quality of CRR.