Enhancing Neuronal Networks with Rhinella schneideri Skin Secretion Molecules: Implications for Neurodegenerative Disorders

Neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases, are hallmarked by the progressive degeneration of neuronal networks. Given the lack of disease-modifying cures, current therapies are limited to symptomatic relief. Here, we investigated the neurotrophic potential of the skin secretion (SS) from Rhinella schneideri, its polar fraction (PF) and nonpolar (NPF) fraction, and respective subfractions on the morphology of neuron-like cells. Following initial H2O-CH2CL2 partitioning, PF and NPF subfractions were isolated via RP-HPLC. Chemical characterization using LC-MS-IT-TOF identified eight distinct molecules, notably bufotenine and marinobufagin. Cytotoxicity screening established safe working concentrations (100–250 ng/mL for SS/PF; 250–500 ng/mL for NPF and subfractions) for downstream morphological evaluations using High Content Screening (HCS). The subfraction polar 5 (SfP5) elicited a robust neurotrophic response, significantly enhancing all assessed morphometric parameters: total neurite outgrowth (+72%), branching points (+120%), maximum process length (+60%), and total number of processes (+35%). Our data show that Rhinella schneideri SS contains molecules that improve in vitro neuronal networks, serving as a promising source for preliminary screening of neuroprotective effects.