Abstract

Many different species of Rhodiola are traditional botanical medicines with various effects, and their roots and rhizomes are the medicinal parts, which have been recorded in many ancient medical books. The 2020th edition of Chinese Pharmacopoeia stipulates Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (R. crenulata) as the only medicinal species. However, the wild resources of R. crenulata are gradually decreasing, and it is difficult to achieve artificial cultivation of R. crenulata nowadays. It is important to find several alternative species of R. crenulata. In the present study, an integrated strategy based on chemical profiling, disease module-guided network pharmacology, and quantitative analysis (CDMQ) has been developed to estimate the chemical characteristics, determine active components and related disease modules, discover potential quality markers, and identify alternative species in a step-by-step manner for 9 species of Rhodiola. Firstly, a total of 109 compounds were identified in accordance with their retention times, accurate masses and characteristic MS/MS fragment patterns, which mainly included phenylpropanoid glycosides, gallic acid glycosides, flavonoids and their glycosides, flavanols, organic acids, and others. Subsequently, disease module-guided network pharmacology analysis was performed based on the related targets of 109 compounds. In combination of the limit of detection of the UPLC-QQQ-MS/MS, 12 compounds were identified as active components. The enriched disease modules of circulatory system, mouth, respiratory system, skin and connective tissue showed close relationship with traditional efficacy of Rhodiola species. It also revealed that salidroside, rhodiosin, epicatechin gallate, catechin gallate, and 6′-O-galloylsalidroside changed significantly in different species to be served as potential quality markers for Rhodiola. Among the 9 species, Rhodiola kirilowii (Regel) Maxim (R. kirilowii) and Rhodiola sacra (Prain ex Hamet) S.H. Fu (R. sacra) could probably be used as an alternative species of R. crenulata. Overall, this study established a solid foundation and provided theoretical guidance for the chemical profiling, prediction of clinical application, and quality control of different Rhodiola species.

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