Anxiolytic effects, metabolism and plasma pharmacokinetics of 3, 6′ -disinapoylsucrose

3,6′-disinapoylsucrose (DISS) is a bioactive oligosaccharide ester derived from Polygalae Radix. This study aims to explore the anxiolytic effects of DISS and further reveal the material basis by establishing the pharmacokinetics of DISS and its metabolites. Behavioral experiments such as the open field test (OFT) and elevated plus maze test (EPM) were performed to evaluate the anxiolytic effects of DISS in mice after oral administration. By UPLC-MS/MS analysis, DISS and its metabolites both in blood and cerebrospinal fluid were identified, and the pharmacokinetics of DISS and its metabolites were characterized in SD rats after oral administration of DISS (100 mg·kg−1). Oral DISS could increase the time and frequency of mice entering the central area of the field in OFT and open arm in EPM, which indicated DISS has good anxiolytic effects. We also identified DISS and its metabolites (sinapic acid (SA), 3,4,5-trimethoxycinnamic acid (TMCA), methyl-3,4,5-trimethoxycinnamate (TMCA-CH2), p-Coumaric acid (CA) and p-methoxycinnamic acid (MA)) in rat plasma and cerebrospinal fluid. The pharmacokinetic results showed that DISS was rapidly absorbed after administration and reached its highest concentration at 12 min, SA had the highest exposure level in vivo and was probably the main active form of DISS action, TMCA could maintain at a low concentration for a long time. In brief, we reported the anxiolytic effect of DISS firstly, revealed the cerebrospinal fluid distribution and pharmacokinetics of DISS and its metabolites. Our findings provide the basis for further insight into the mechanisms involved in the anxiolytic effects of DISS.