Comparison of Phytochemical Composition and Untargeted Metabolomic Analysis of an Extract from Cnidoscolus aconitifolius (Mill.) I. I. Johnst and Porophyllum ruderale (Jacq.) Cass. and Biological Cytotoxic and Antiproliferative Activity In Vitro.

Cnidoscolus aconitifolius (CA) and Porophyllum ruderale (PR) are representative edible plants that are a traditional food source in Mexico. This research aimed to analyze the phytochemical composition and untargeted metabolomics analysis of CA and PR and evaluate their antiproliferative effect in vitro. The phytochemical composition (UPLC-DAD-QToF/MS-ESI) identified up to 38 polyphenols and selected organic acids that were clustered by the untargeted metabolomics in functional activities linked to indolizidines, pyridines, and organic acids. Compared with PR, CA displayed a higher reduction in the metabolic activity of human SW480 colon adenocarcinoma cells (LC50: 10.65 mg/mL), and both extracts increased the total apoptotic cells and arrested cell cycle at G0/G1 phase. PR increased mRNA Apc gene expression, whereas both extracts reduced mRNA Kras expression. Rutin/epigallocatechin gallate displayed the highest affinity to APC and K-RAS proteins in silico. Further research is needed to experiment on other cell lines. Results suggested that CA and PR are polyphenol-rich plant sources exhibiting antiproliferative effects in vitro.

Signals from the caudal diencephalon are required for the projection of the Interstitial Nuclei of Cajal.

Axonal projection is controlled by discrete regions localized at the neuroepithelium, guiding the neurite growth during embryonic development. These regions exert their effect through the expression of a family of chemotropic molecules, which actively participate in the formation of neuronal connections of the central nervous system in vertebrates. Previous studies describe prosomere 1 (P1) as a possible organizer of axonal growth of the rostral rhombencephalon, contributing to the caudal projection of reticulospinal rhombencephalic neurons. This work studies the contribution of chemotropic signals from P1 or pretectal medial longitudinal fascicle (MLF) neurons upon the caudal projection of the interstitial nuclei of Cajal (INC). By using in ovo surgeries, retrograde axonal labeling, and immunohistochemical techniques, we were able to determine that the absence of P1 generates a failure in the INC caudal projection, while drastically diminishing the reticulospinal rhombencephalic neurons projections. The lack of INC projection significantly decreases the number of reticulospinal neurons projecting to the MLF. We found a 48.6% decrease in the projections to the MLF from the rostral and bulbar areas. Similarly, the observed decrease at prosomere 2 was 51.5%, with 61.8% and 32.4% for prosomeres 3 and 4, respectively; thus, constituting the most affected rostral regions. These results suggest the following possibilities: i, that the axons of the reticulospinal neurons employ the INC projection as a scaffold, fasciculating with this pioneer projection; and ii, that the P1 region, including pretectal MLF neurons, exerts a chemotropic effect upon the INC caudal projection. Nonetheless the identification of these chemotropic signals is still a pending task.