The mechanisms of action underlying the pharmacological properties of the natural alkaloid berberine still
need investigation. Planarian regeneration is instrumental in deciphering developmental responses
following drug exposure. Here we report the effects of berberine on regeneration in the planarian Dugesia
japonica. Our findings demonstrate that this compound perturbs the regenerative pattern. By real-time
PCR screening for the effects of berberine exposure on gene expression, we identified alterations in the
transcriptional profile of genes representative of different tissues, as well as of genes involved in extracellular
matrix (ECM) remodeling. Although berberine does not influence cell proliferation/apoptosis, our
experiments prove that this compound causes abnormal regeneration of the planarian visual system.
Potential berberine-induced cytotoxic effects were noticed in the intestine. Although we were unable to
detect abnormalities in other structures, our findings, sustained by RNAi-based investigations, support the
possibility that berberine effects are critically linked to anomalous ECM remodeling in treated planarians
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