In vitro and in vivo evaluation of the influences of polysaccharides derived from Glycyrrhiza uralensis on three alkaloids and potential interaction mechanisms

The purpose of this study was to investigate the influences of the polysaccharides derived from Glycyrrhiza uralensis Fisch. (GCPs) on aconitine (AC), hypaconitine (HA), and benzoylmesaconine (BMA) from Aconitum carmichaelii Debx. and to explore potential interaction mechanisms. Biopharmaceutical properties in vitro including stability, aqueous solubility and permeability were determined by UPLC. Pharmacokinetic parameters in vivo were determined using UPLC-MS/MS. Phase solubility analysis, UV–vis spectrophotometry and differential scanning calorimetry (DSC) were used to explore potential interaction mechanisms. The results showed that GCPs could increase the stabilities of three alkaloids and solubilities of AC and HA, significantly decrease permeabilities of three alkaloids. The pharmacokinetic studies demonstrated that, after combination with GCPs, AC exhibited a higher Cmax value, shorter t0.5, higher elimination rate and greater area under the concentration-time curve (AUC) value compared to free AC. GCPs also improved the Cmax, t0.5, AUC(0–tn) and AUC(0–∞) values of HA to play a therapeutic role, and improved the t0.5 and AUC(0–∞) values of BMA to prolong the pharmacological effect and increase bioavailability. In addition, the results for the apparent formation constants and DSC analysis showed that an inclusion complex could be formed between GCPs and AC, GCPs and HA, and GCPs and BMA.