Project description:Cardiac glycosides (CGs) are good candidates as drug leads in the treatment of cancer because of their structural diversities and potent biological activities. In this study, fifteen CGs including three new ones (1-3) were isolated from Digitalis lanata Ehrh. Their structures were elucidated by HRESIMS, NMR spectroscopic methods, including homonuclear and heteronuclear coupling constant analysis, and acid-catalyzed hydrolysis and derivatization analysis of the sugar chain. The cytotoxic activities of these CGs were evaluated against three human cancer cell lines (A549, HeLa and MCF-7 cell lines), and all of them showed strong activities at nanomolar scale. The flow cytometric analysis indicated that compound 1 induced cell cycle arrest in the G2/M phase. Transcriptome analysis revealed a panel of possible targets for compound 1. RT-PCR and western blot experiments showed that 1 significantly inhibited the expression of vasohibin-2 (VASH2). Moreover, compound 1 restrained angiogenesis in a concentration-dependent manner in the chick embryo chorioallantoic membrane (CAM) model.
Project description:Climatic fluctuations during the Quaternary significantly affect many species in their intraspecific divergence and population structure across northwest China. In order to investigate the impact of climate change on herbaceous plants, we studied Panzerina lanata (Lamiaceae), a widely distributed species. Sequences of two chloroplast DNA (cpDNA) intergenic spacers (trnH-psbA and rpoB-trnC) and a nuclear ribosomal region (nrDNA, ITS) were generated from 27 populations of Panzerina lanata and resulted in the identification of seven chloroplast haplotypes and thirty-two nuclear haplotypes. We applied AMOVA, neutrality test and mismatch distribution analysis to estimate genetic differentiation and demographic characteristics. The divergence times of the seven cpDNA haplotypes were estimated using BEAST. Our results revealed high levels of genetic diversity (cpDNA: Hcp = 0.6691, H T = 0.673; nrDNA: Hnr = 0.5668, H T = 0.577). High level of genetic differentiation (G ST = 0.950) among populations was observed in the cpDNA sequences, while the genetic differentiation values (G ST = 0.348) were low in nuclear sequences. AMOVA results revealed major genetic variation among the three groups: northern, central, and eastern group. However, the genetic differentiation in ITS data was not found. The species distribution modeling and demographic analysis indicated that P. lanata had not experienced recent range expansion. The occurrence of divergence between seven cpDNA haplotypes, probably during Pleistocene, coincides with aridification and expansion of the desert across northwest China that resulted in species diversification and habitat fragmentation. In addition, we discovered that the deserts and the Helan Mountains acted as effective geographic barriers that promoting the intraspecific diversity of P. lanata.