Pharmacokinetic study of eighteen components from aqueous extract of Corydalis Decumbentis Rhizoma in normal and MCAO rats.

Ethnopharmacological Relevance: As a traditional Chinese medicine, Corydalis Decumbentis Rhizoma (Xiatianwu, XTW) is known for its beneficial effects in dispelling wind-dampness, promoting blood circulation, and alleviating pain. Conducting detailed pharmacokinetic studies on the bioavailable components of XTW will contribute to its scientific and rational development.

Aim Of The Study: To explore and explain the pharmacokinetic characteristics of different types of isoquinoline alkaloids and the differences in their pharmacokinetic parameters between normal and middle cerebral artery occlusion (MCAO) model groups following oral administration of aqueous extract of XTW.

Materials And Methods: This study established a quantitative method for the simultaneous determination of 18 alkaloids in rat plasma via ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-TQ-MS/MS). The 18 alkaloids were then quantified in the plasma of normal and MCAO rats following a single oral gavage of aqueous extract of XTW.

Results: The quantitative method developed via UPLC-TQ-MS/MS demonstrated excellent selectivity, specificity, linearity, precision, accuracy, matrix effects, recoveries, stability, dilution reliability and carry-over. Following the administration of three doses of XTW, the AUC values of 5 compounds, hydrohydrastinine, corypalmine, tetrahydropalmatine, allocryptopine, and muramine, showed strong linear correlations with the administered doses. At the low dose, 16 out of 18 compounds in the normal group were rapidly absorbed (T < 2 h) and the C of oxyhydrastinine and tetrahydropalmatine both exceeded 100 ng/mL. Compared with those of normal rats, the AUC values of 16 compounds tended to increase in MCAO rats, with a significant increase observed for 8 compounds.

Conclusion: After an oral administration of aqueous extract of XTW to rats, the compounds generally exhibited rapid absorption and elimination. Moreover, slight structural differences could lead to significant variations in pharmacokinetic properties, which may be closely related to the selectivity of intestinal bacteria, transporters, and metabolic enzymes involved in in vivo processes. Pathological damage in MCAO rats could significantly alter pharmacokinetic behaviors after oral administration of XTW aqueous extract, primarily manifesting as increased absorption and in vivo exposure. The results of pharmacokinetics of three single doses in normal rats and comparative pharmacokinetics in normal and MCAO rats provide valuable insights for elucidating the pharmacological substances in XTW and identifying more suitable lead compounds.