Total coumarins in Pileostegia tomentella inhibits proliferation of small cell lung cancer H1688 cells by inducing ferroptosis / 中国药理学通报

Aim To explore the mechanism by which total coumarins in Pileostegia tomentella (TCPT) inhibits the proliferation of small cell lung cancer (SCLC) H1688 cells via inducing ferroptosis. Methods The gradient concentrations of TCPT were used to treat H1688 cells. CCK-8 assay was applied for detection of proliferative inhibition of H1688 cells. Transmission electron microscopy was used to approach the morphological changes of H1688 cells under the treatment of TCPT. Additionally, dichlorofluorescein (DCFH-DA) probe was used to detect the intracellular reactive oxygen species (ROS) level. BODIPY 581/ 589 Cll probe was applied to examine the intracellular lipid peroxide formation. Western blotting was employed to detect the expression levels of glutathione peroxidase 4 (GPX4), kelch-like ECH-associated protein (KEAP1), nuclear factor E2 related factor 2 (NRF2), ferritin heavy chain 1 (FTH1) proteins in HI688 cells. Results The proliferation of small cell lung cancer cell H1688 was dramatically inhibited after TCPT intervention (P < 0. 05, P < 0. 01). The morphological characteristics of ferroptosis induced by TCPT were observed by transmission electron microscope. TCPT could also effectively elevate intracellular level of ROS and lipid peroxide. In HI688 cells the expression of ferroptosis markers GPX4, NRF2, and FTH1 was down-regulated, while the expression of KEAP1 was up-regulated, and there were statistically significant differences among the markers mentioned a-bove (P<0. 01). Conclusions Total coumarins in TCPT can significantly inhibit the proliferation of H1688 cells, possibly through increasing ROS and intracellular lipid peroxide levels and eventually inducing ferroptosis.

Analysis of Chemical Constituents and Activity on Zanthoxylum nitidum Husk / 中国实验方剂学杂志

Objective:To analyze and identify the non-medicinal parts in Zanthoxylum nitidum husk by HPLC-LTQ/Orbitrap-MS, and study the antioxidant activity, in order to provide the scientific basis for further research and development of Z. nitidum. Method:Data is collected by HPLC-LTQ/Orbitrap-MS,and high-resolution MS and MS2 spectra of mass spectrogram of chromatographic peaks were analyzed and compared with the literature database. The structure of each chromatographic peak was calculated and confirmed. The anti-oxidative activity of the Z. nitidum husk was studied by DPPH scavenging free radical ability and ABTS free radical scavenging ability. Result:Twenty-five alkaloids were identified from Z. nitidum husk. The main constituents were isoquinoline alkaloids (nitidine,liriodenine,magnocurarine),pyrrolidine alkaloid (allocryptopine,oxymatrine,oxysophocarpine),quinoline alkaloid (magnoflorine,nitidine chloride),and organic amine alkaloids (γ-sanshool). Antioxygenic activity was studied by DPPH scavenging free radical ability and ABTS free radical scavenging ability. The results showed that they were within the measured concentration range, the antioxidant activity increased with the rise of the sample concentration, a good dose dependence was presented. Conclusion:In this paper,the chemical constituents and the activity Z. nitidum husk were studied. Studies have shown a variety of alkaloids, with a good antioxidant activity. This study provides a reference for further research and development of Z. nitidum.