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

Abstract

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 > 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.