The metabolism of salidroside to its aglycone p-tyrosol in rats following the administration of salidroside

Abstract

Salidroside is one of the major phenolic glycosides in Rhodiola, which has been reported to possess various biological activities. In the present study the in vivo deglycosylation metabolism of salidroside was investigated and its aglycone p-tyrosol but not the original salidroside was identified as the main form in rat tissues following the administration of salidroside. After the i.v. administration of salidroside at a dose of 50 mg/kg in rats, salidroside was quantified only in the liver, kidney and heart tissues. The highest level of p-tyrosol was detected in the heart, followed by the spleen, kidney, liver and lungs, in order. Salidroside was detected only in the liver, in contrast, p-tyrosol was detectable in most tissues except the brain, and the kidney tissues contained a significant amount of p-tyrosol compared to the other tissues after the i.g. administration of 100 mg/kg salidroside. The excretion behaviour revealed that the administrated salidroside mainly eliminated in the form of salidroside but not its aglycone metabolite p-tyrosol through urine. After i.v. and i.g. administration in rats, 64.00% and 23.80% of the total dose was excreted through urine in the form of salidroside, respectively. In addition, 0.19% and 2.25% of the dose was excreted in the form of p-tyrosol through urine after i.v. and i.g. administration, respectively. The faecal salidroside and p-tyrosol concentrations were 0.3% and 1.48% of the total dose after i.v. administration, respectively. After the i.g. administration of salidroside, trace salidroside and p-tyrosol were quantified in faeces within 72 h. In addition, the biliary excretion levels of salidroside after i.v. and i.g. administration were 2.86% and 0.02% of the dose, respectively. The obtained results show that salidroside was extensively metabolised to its aglycone p-tyrosol and distributed to various organs and the original salidroside was cleared rapidly through urine following the administration of salidroside.

Figure 1. Chemical structures of (A) salidroside, (B) p-tyrosol and (C) paracetamol (IS).

Figure 2. MRM chromatograms of salidroside, p-tyrosol and the IS in (A) a blank rat liver tissue homogenate sample, (B) a blank rat liver tissue sample spiked with salidroside (500 ng/mL), p-tyrosol (500 ng/mL) and the IS (200 ng/mL), (C) a rat liver tissue homogenate sample collected 0.17 h after i.v. administration of salidroside (50 mg/kg) with the IS (200 ng/mL), (D) a rat liver tissue homogenate sample collected 1 h after i.g. administration of salidroside (100 mg/kg) with the IS (200 ng/mL).

Figure 3. Mean concentration-time profiles of (A) salidroside and (B) p-tyrosol in rat tissues (n = 6) obtained after i.v. administration of salidroside (i.v. 50 mg/kg).

Figure 4. Mean concentration-time profiles of (A) salidroside and (B) p-tyrosol in rat tissues (n = 6) obtained after i.g. administration of salidroside (i.g. 100 mg/kg).