Integrated widely targeted metabolomics and network pharmacology revealed quality disparities between Guizhou and conventional producing areas of Codonopsis Radix.

Abstract

With the internationalization of traditional Chinese medicine, the demand for medicinal and edible Codonopsis Radix (CR) has increased, and its medicinal resources have attracted attention. CR is a well-known traditional Chinese medicine with a long pharmaceutical and edible history. The Guizhou province in China has abundant CR resources, but in the absence of systematic studies on species identification and chemical compositions, the capacity of the capacity of the province to CR resource has not been fully utilized. We used plant morphology and DNA barcoding techniques to identify Luodang (LD) and Weidang (WD) species. To investigate the differences in metabolites between LD and WD, as well as three Chinese Pharmacopeia CRs, and to predict pharmacological mechanisms of action for the dominant differential metabolites, we utilized widely targeted metabolomics and network pharmacology. The results also revealed the material basis for the excellent food properties of both LD and WD. The plant traits and DNA barcoding molecular identification results indicated that Luodang and Weidang from Guizhou were Codonopsis tangshen and Codonopsis pilosula, respectively. Widely targeted metabolomics analysis revealed that a total of 1,116 metabolites from 14 categories, including phenolic acids, lipids, flavonoids, were found in five CRs and shared 1,054 (94.4%) metabolites. LD and WD each contained 3 and 10 dominant differential metabolites, respectively, which were primarily flavonoids and amino acids. Amino acids, phenolic acids, and organic acids play important roles in their excellent food attributes. In CR, eight dominant differential metabolites were discovered for the first time, including isoorientin-7-O-(6″-feruloyl) glucoside, N-formyl-L-methionine, and cyclo (Phe-Glu), among others. Network pharmacology analyses showed that, in LD, dominant differential metabolites were closely related to anti-tumor, cardiovascular disease improvement, nervous system protection, and metabolic disease treatment, whereas in WD, they were closely related to nervous system protection and cardiovascular disease improvement. The species of LD and WD were included in the Chinese Pharmacopeia, and their metabolite profiles were remarkably similar to CR from traditional producing areas. Therefore, LD and WD can be used and promoted medicinally as CR, and they have potential value for new drug development. This study enriched the database of CR compounds and provided a reference for quality control, resource development, and new drug development of CR.