Absorption characteristics of ilexgenin A and ilexsaponin B1 in human umbilical vein endothelial cells after administration of the total triterpenoid saponin from <i>Ilex Pubescens</i>

Ilex pubescens, a famous Chinese herbal medicine, frequently treated with cardiovascular disease in South China. In this study, we aim to explore the absorption properties of ilexgenin A (C1) and ilexsaponin B1 (C3) in vascular endothelial cells after administration of the total triterpenoid saponin from Ilex Pubescens (IPTS) and clarify the possible transport mechanisms. A UPLC-qTOF-MS/MS was used to identify the components in IPTS that could be intracellular transported by HUVECs. Afterwards, a rapid, high selective and sensitive methods was established to simultaneously quantify the concentration of C1 and C3 in HUVECs after administration of IPTS. The results demonstrated that pretreatment with IPTS could promote the survival of HUVECs and reduce the damage of TNF-α to HUVECs. Among the main 11 components in IPTS, 8 components could be absorbed by HUVECs, including 7 triterpenoids and 1 phenolic acid. The uptake of C1 and C3 by HUVECs was in a time-, temperature- and concentration-dependent manner, indicating the participation of passive diffusion and active transportation mechanisms. The two triterpenoid saponins all exhibited rapid absorption and bimodal phenomenon in concentration-time profiles, and equilibrium could be achieved after 6 hours. Furthermore, C1 and C3 intracellular transportation was regulated by serum proteins, sodim-dependent glucose transporter 1 (SGLT1) and P-glycoprotein (P-gp). The current research for the first time demonstrates the in vitro pharmacokinetics characteristics of C1 and C3 in HUVECs lines, which could supply new way of understanding of treatment of cardiovascular diseases.