Polydatin (3,4',5-trihydroxystilbene-3-β-D-glucoside, piceid), a natural stilbenoid found in different plant sources, has gained increasing attention for its potential health benefits. However, prior to its widespread adoption in human therapeutics and consumer products, a comprehensive investigation of its toxicological effects is crucial. In this study, the toxicity of polydatin was investigated in a developmental toxicity test using zebrafish (Danio rerio) as a valuable model for preclinical assessments. We employed the Fish Embryo Test (FET test - OECD n°236) to investigate the effects of polydatin on survival, hatchability, development, and behavior of zebrafish embryo-larval stage. Remarkably, the results demonstrated that polydatin up to 435 μM showed no toxicity. Throughout the exposure period, zebrafish embryos exposed to polydatin exhibited normal development, with no significant mortality observed. Furthermore, hatching success and heartbeat rate were unaffected, and no morphological abnormalities were identified, signifying a lack of teratogenic effects and cardiotoxicity. Locomotion activity assessment revealed normal swimming patterns and response to stimuli, indicating no neurotoxic effects. Our study provides valuable insights into the toxicological profile of polydatin, suggesting that it may offer potential therapeutic benefits under a considerable concentration range. In addition, zebrafish model proves to be an efficient system for early-stage toxicological screening, guiding further investigations into the secure utilization of polydatin for human health and wellness.

Resveratrol (RV), a natural polyphenol, has been extensively studied for its neuroprotective potential in Parkinson's Disease (PD), but its clinical translation is limited by poor bioavailability and rapid metabolism. Glycosylated derivatives, including polydatin and resveratrol-3-α-glucoside, have been proposed to improve the solubility and stability. This study compared the pharmacokinetic properties of RV and its derivatives and examined their molecular interactions with PD-related targets. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis showed that, despite improved solubility, RV retained a more favorable overall pharmacokinetic profile. Target prediction combined with Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network construction identified 50 potential targets, with 11 prioritized for molecular docking. Glycosylated derivatives exhibited binding affinities for all targets stronger than those of RV, with TNF-α, PPARγ, and ERBB2 highlighted as key candidates. These findings indicate that RV glycosylation may enhance therapeutic potential for PD treatment by promoting stronger molecular interactions with critical targets, though in vivo validation remains necessary.

Background/Objectives: Epilepsy is a common neurological condition characterized by the occurrence of a seizure. It affects around 50 million individuals worldwide, and despite the large quantity of anti-seizure medications available, 30% of epileptic patients still suffer from seizures. Therefore, it is necessary to find new therapeutic options. Interestingly, polydatin has shown promising effects on epilepsy treatment due to its antioxidant and anti-inflammatory properties. Thus, this study aimed to evaluate the effects of polydatin (200, 300, and 400 µM) on a pentylenetetrazol (PTZ)-induced seizure model in wild-type zebrafish (Danio rerio) larvae. Methods: Seizure-like behavior, cell death, reactive species (RS) production, and lipid peroxidation were analyzed. Results: Pre-treatment with polydatin at 200 and 300 µM did not have a significant impact on seizure occurrence and the behavior of animals exposed to PTZ. Diazepam decreased seizure occurrence and increased the latency to achieve each seizure stage. Exposure to PTZ increased the swimming activity, and this effect was suppressed by diazepam but not by polydatin. PTZ exposure increased the RS production, which was significantly attenuated by polydatin at 400 µM and DMSO. Cell death and lipid peroxidation were not changed when compared to the experimental groups. Conclusions: Only the experimental positive control (diazepam) showed anti-seizure effects. Therefore, we failed to observe any anti-seizure effects of polydatin using a zebrafish experimental model. However, we cannot rule out its effects in other experimental models and different treatment protocols.