Metabolomics and molecular networking approaches reveal differential metabolites of Radix Scrophulariae from different geographical origins: Correlations with climatic factors and biochemical compounds in soil

Abstract Radix Scrophulariae (RS) is a well-known and frequently used traditional Chinese medicine. Cultivated RS from Zhejiang province is considered to be superior in quality to that from other provinces in China. However, the contribution of geographical origins to differential metabolite production in RS is unclear. In this study, we used ultrahigh-performance liquid chromatography-quadrupole-orbitrap mass spectrometry-based metabolomics and molecular networking to examine differential metabolites in RS samples from different origins and explore their correlations with climatic factors and biochemical compounds in soil. nineteen compounds were identified as the important differential metabolites in RS from different origins, including two oligosaccharides, six cinnamoyl derivatives, four p-coumaroyl derivatives, three caffeoyl derivatives, two feruloyl derivatives, and three methoxycinnamoyl derivatives. However, harpagide and harpagoside, two chemical markers in Chinese Pharmacopoeia, were not among the differential metabolites. Moreover, 18 compounds having higher contents in RS from Zhejiang than in that from other provinces, emerged as candidate chemical markers of quality control. The contents of differential metabolites were negatively correlated with humidity and precipitation in October and positively correlated with evaporation and surface temperature. This study provides a foundation for further research on the quality control, pharmacological activity, and product development of RS from Zhejiang and a useful strategy for further optimizing the cultivation process of RS.