In vivo effects of natural compounds present in Chelidonium majus on stem cells using a simple animal model

Planarians are a well-known model for regeneration and provide an excellent system to study the behavior of stem cells in vivo. Despite the potential attractiveness of planarians these organisms have not been used yet in large-scale chemical screenings to see the effects of compounds on different key aspects of regeneration as, for instance, stem cell proliferation and differentiation. Our work focuses on the analysis of the effects produced by the main alkaloids (chelidonine, berberine, sanguinarine, chelerytrine, protopine and coptisine) present in Chelidonium majus (Papaveraceae), an herb showing interesting therapeutical properties. We demonstrate that chelidonine produces a significant anti-proliferative effect on planarian stem cells, supporting the possibility that this alkaloid acts on cell cycle progression by inhibition of tubulin polymerization. Berberine treatment perturbs the regenerative pattern. Although berberine does not influence cell proliferation/apoptosis, this compound causes abnormal regeneration of the planarian visual system. Our findings, sustained by RNAi-based investigations, support the possibility that berberine effects are critically linked to anomalous extracellular matrix remodeling. Abnormal head regeneration has also been observed following sanguinarine treatment. Preliminary results provide evidence that sanguinarine induces apoptosis through a caspase-dependent mechanism, but does not influence cell proliferation. The study presented here might become a good test to determine the potentiality of planarians as a model to analyze drug effects. At the same time, such screenings and experiments could help to better understand the process of planarian regeneration itself by providing novel information about how proliferation, differentiation and/or morphogenesis and patterning are regulated during this amazing process.