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Peimine and peiminine are isosteroidal alkaloids with multiple biological activities, such as anticancer and anti-inflammatory activities, but their cellular uptake and pharmacodynamics are unclear. In this study, a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous quantification of peimine and peiminine concentrations in A549 cells. In the pharmacodynamic study, the selected inflammatory cytokines were IL-8, MMP-9, and TIMP-1. The results demonstrated that all calibration curves exhibited good linearity (r &gt; 0.9970). The RSDs of intraday and interday precision and accuracy were less than 6.73% and 1.76% and 7.73% and 3.05% for peimine and peiminine, respectively. Moreover, the average analytic recoveries ranged from 83.85% to 113.67%, and the matrix effect was within 95.05%–111.29%. The uptake experiment showed a time-dependent characteristic in the A549 cells. The combination group had increased uptake and had a longer Tmax than the single group. In the experimental pharmacodynamics groups, the anti-inflammatory effects of the 100.0 µg/mL combination group were the most obvious. This investigation, for the first time, explores the cellular uptake profiles and pharmacodynamics of peimine and peiminine in A549 cell lines.

Pharmacodynamics and Cellular Uptake of Peimine and Peiminine in Inflammatory Model Non-Small-Cell Lung Cancer Epithelial Cells (A549)