An Approach to Characterizing the Complicated Sequential Metabolism of Salidroside in Rats

Abstract

Metabolic study of bioactive compounds that undergo a dynamic and sequential process of metabolism is still a great challenge. Salidroside, one of the most active ingredients of Rhodiola crenulata, can be metabolized in different sites before being absorbed into the systemic blood stream. This study proposed an approach for describing the sequential biotransformation process of salidroside based on comparative analysis. In vitro incubation, in situ closed-loop and in vivo blood sampling were used to determine the relative contribution of each site to the total metabolism of salidroside. The results showed that salidroside was stable in digestive juice, and it was metabolized primarily by the liver and the intestinal flora and to a lesser extent by the gut wall. The sequential metabolism method described in this study could be a general approach to characterizing the metabolic routes in the digestive system for natural products.

Cytosolic β-glucosidase inhibition and renal blood flow suppression are leading causes for the enhanced systemic exposure of salidroside in hypoxic rats

“…p-Tyrosol sulfate was the predominant metabolite identied in the hepatic metabolism of SAL, which accounted for over 50% of the total metabolites in systemic circulation. 10,11 The formation rate of p-tyrosol sulfate could therefore serve as an indicator for the hepatic metabolic rate of SAL. The liver S9 fraction (RLS) derived from 5 normoxic rats and 5 hypoxic rats were prepared respectively according to previously mentioned method.…”

“…7a and b). 10,11 It was noticed that the formations of p-tyrosol sulfate were only dramatically inhibited when SAL was incubated with RLS in the presence of CBG inhibitor, suggesting the potential roles of CBG in the deglycosylation of SAL in rats. Moreover, the formations of p-tyrosol sulfate were signicantly inhibited when p-tyrosol was incubated with RLS in the presence of SULT2A1 inhibitor, suggesting the potential roles of SULT2A1 in the sulfation of SAL in rats.…”

“…1c) in systemic circulation turns out to be the sulfate form of SAL aglycone (p-tyrosol). 10,11 There are indeed speculations suggesting that hypoxia alters pharmacokinetics of some drug by suppressing the cytochrome P450 (CYP) enzymes, but the effect of hypoxia on SGLT1, glycosidase and sulfotransferase (SULT) has never been explored. 12 Since about 20% of administered SAL is excreted from urine in the form of parent compound, whether hypoxia alters the renal function of rats also deserve further investigation.…”

Therapeutic potential of phenylethanoid glycosides: A systematic review

“…The nine metabolic pathways of poliumoside were proposed as rearrangement, reduction, hydroxylation, hydration, dehydration, methylation, acetylation, hydrolyzation, and sulfation, 216 which are partly in accordance with the result of Deng et al 215 Metabolites of salidroside in rats plasma samples indicated that salidroside was metabolized through glucuronidation, deglycosylation, sulfation, methylation, hydroxylation, and dehydroxylation in vivo. 217 After po administration of C. tubulosa extract (400 mg/kg), the in vivo metabolites in urine and fecal were obviously different in healthy and chronic unpredictable stress model rats. The metabolic ability to generate secondary glycosides and aglycones in depressive rat intestinal microbiota was much weaker than that in normal rat intestinal microbiota.…”

Identification of the Major Components of Buddleja officinalis Extract and Their Metabolites in Rat Urine by UHPLC‐LTQ‐Orbitrap

“…Liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS) has recently become a powerful and reliable analytical technique for metabolite identification in vivo (Liu and others ; Luo and others ). Urine is recognized as an ideal biological matrix to investigate in vivo metabolic patterns (Hu and others ).…”