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UPLC-QTOF-MS identification of metabolites in rat biosamples after oral administration of Dioscorea saponins: A comparative study

Journal name:Journal of Ethnopharmacology
Document No.:Doi:10.1016/j.jep.2015.02.017
Document URL: http://www.sciencedirect.com/science/article/pii/S0378874115000951
Date publication: 13 May 2015


Ethnopharmacological relevance


Among the 49 species of the genus Dioscorea distributed in China, Dioscorea nipponica Makino (DN), Dioscorea panthaica Prain et Burkill (DP), and Dioscorea zingiberensis C. H. Wright (DZ) possess more or less similar traditional therapeutic actions, such as activating blood, relieving pain, and dispersing swelling; they have been used as folk medicine in China since 1950s. The modern pharmaceutical industry has developed these three species as herbal medicines that have been used for decades for treating cardiovascular diseases. However, there is no available information in the literature explaining how their chemical components are converted and interrelated in vivo to support their efficacies. The present study aimed to a) compare the metabolic profiles of saponins from DN, DP and DZ, which are considered to be their bioactive components, and b) to compare the changes in sustained levels of metabolites from rat biosamples.


Material and methods


Total saponins (TS) from each of the three species, and four individual saponins, namely protodioscin (PD), pseudoprotodioscin (PSD), dioscin (DC) and diosgenin (DG), were given to rats by oral administration. Chemical profiles of the rats? plasma, urine and feces were monitored 1–36 h. A UPLC-QTOF-MS based method was performed to identify the absorbed constituents and their metabolic products in rat biosamples (i.e., blood, urine, and feces); the ratio of peak area of major saponins to that of internal standard was calculated and plotted versus time to characterize the sustained levels of saponins in biosamples.




Totally 10 saponin-related compounds were detected in rat plasma, 10 in rat urine and 18 in rat feces. The results indicated that formation of diosgenin by desugarization was the main pathway by which steroidal glycosides were metabolized. Other types of bio-transformation were found among glycosides and aglycones, such as ring cyclization through loss of 26-O-glucosyl, substitution of β-d-glucopyranosyl for α-l-rhamnopyrannosyl, hydrogenation of diosgenin at 5(6)-double bond, and hydration of 20(22)-double bond. Generally, the metabolic profiles of DN and DP were shown to be quite similar, but different from that of DZ. However, some particular similarities and connections were found among these three TS. Diosgenin was one of the main metabolites commonly found in plasma and feces (excluding urine), from all groups receiving different TS, as well as individual saponins; this is likely to be one of the bioactive constituents playing an essential role in cardioprotective efficacy. Furostane-type saponins in TS of DN, DP or DZ, such as PD, protogracillin, parvifloside, protodeltonin and protobioside, showed fast absorption into blood (<1 h), but were maintained for a relatively short period (mostly<8 h), while the spirostane-type saponin and sapogenin (DC and DG, respectively), were absorbed into circulation more slowly (>1 h), but increased gradually and lasted longer (>36 h). These two patterns suggest that the therapeutic effect of these Dioscorea saponins is achieved through a complex, multi-step process over time. In addition, it appears that PD, PSD, and DC contained in DN and DP were transformed into certain glycosides originally found in DZ but not in DN or DP (protodeltonin, deltonin, trillin, and progenin II), which might indicate another linkage among these three species.




These similarities and connections described above constitute evidence supporting similarity in efficacy of these three herbs from the perspective of metabolism. The UPLC-QTOF-MS based method is accurate and efficient for analyzing metabolic changes in rat biosamples over time.


Ginsenoside Rc (RC) and ruscogenin (RG) used as internal standards for analysis of glycoside and aglycone, respectively, were purchased from Herbpurify Co., Ltd. ...

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