Abstract
Pharmacokinetic and metabolism studies were carried out on curculigoside C (CC), a natural product with good antioxidant and neuroprotective effects, with the purpose of investigating the effects of the hydroxyl group at C-3′ in curculigoside. A rapid and sensitive method with UPLC-MS was developed and fully validated for the first time in the pharmacokinetic analysis for quantification of CC in rat plasma. The assay was linear (R2 > 0.9984) over the concentration range of 1–2500 ng/mL, with the lower limit of quantification (LLOQ) being 1 ng/mL. The intra-day and inter-day precision (expressed as relative standard deviation, RSD) ranged from 4.10% to 5.51% and 5.24% to 6.81%, respectively. The accuracy (relative error, RE) ranged from −3.28% to 0.56% and −5.83% to −1.44%, respectively. The recoveries ranged from 92.14% to 95.22%. This method was then applied to a pharmacokinetic study of rats after intragastric administration of 15, 30 and 60 mg/kg CC. The results revealed that CC exhibited rapid oral absorption (Tmax = 0.106 h, 0.111 h, and 0.111 h, respectively), high elimination (t1/2 = 2.022 h, 2.061 h, and 2.048 h, respectively) and low absolute bioavailability (2.01, 2.13, and 2.39%, respectively). Furthermore, an investigation on the metabolism of CC was performed by UPLC-QTOF-MSE. Twelve metabolites of CC from plasma, bile, urine and faeces of rats were confirmed. The main metabolic pathways of CC, which involve dehydration, glucosylation, desaturation, formylation, cysteine conjugation, demethylation and sulfonation, were profiled. In conclusion, this research has developed a sensitive quantitative method and demonstrated the metabolism of CC in vivo.
Highlights
Curculiginis rhizoma, the dried rhizome of Curculigo orchioides Gaertn, is rich in phenolic glycosides [1,2]
The pharmacokinetic analysis elucidated that curculigoside C (CC) was rapidly absorbed and quickly eliminated, which is similar to curculigoside A, but CC showed better bioavailability (2.39%) than that of curculigoside A (0.38%) [15], which might be the reason for the better activity of CC
The extraction recovery of CC from rat plasma at three quality control (QC) concentrations was assessed by comparing peak areas of the QC samples pre-spiked in blank plasma (A) with those of post-extracted blank plasma spiked at the same concentration (B)
Summary
Curculiginis rhizoma, the dried rhizome of Curculigo orchioides Gaertn, is rich in phenolic glycosides [1,2]. Curculigosides have been demonstrated to be the major components responsible for the pharmacological effects of Curculiginis rhizoma [3,4,5,6]. Several curculigosides have been isolated from Curculiginis rhizoma so far, such as curculigosides A, -B,. Due to its highest content in Curculiginis rhizoma, curculigoside A has been the main curculigoside studied for its pharmacological effects [10,11,12,13] and pharmacokinetic profiles [14,15]. Curculigoside C (CC) is the natural product of C-30 hydroxylation of curculigoside A [16]. It was reported that CC has better antioxidant and neuroprotective effects that the parent compound [17,18]
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