Acute developmental toxicity and cardiotoxicity of Physalis alkekengi L. fruit and calyx extracts based on zebrafish (Danio rerio) model

Ethnopharmacological relevance Physalis alkekengi L. ( P. alkekengi ) is widely used in traditional medicine and functional foods for its various medicinal properties. However, its toxicological profile has not been comprehensively assessed. Aim of the study This study aimed to characterize the developmental toxicity and cardiotoxicity of P. alkekengi using a Danio rerio ( D. rerio ) embryo model and to identify key toxic constituents to support safety optimization. Materials and methods D. rerio embryos were exposed to the fruit and calyx extracts of P. alkekengi as well as membrane-fractionated preparations to assess toxic phenotypes. Chemical profiling was performed using ultra-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-Exactive Orbitrap-MS), and mechanistic insights were explored using apoptosis-related assays and network toxicology analysis. Results The fruit extract of P. alkekengi exhibited stronger developmental toxicity and cardiotoxicity effects compared to the calyx extract. The 5–10 kDa non-polysaccharide fraction of the fruit was identified as the primary toxic source, with Glycidyl stearate (GS) being the key cardiotoxic component in this fraction. Removal of the most toxic 5–10 kDa fraction during the extraction process significantly reduced the toxicity of the fruit extract. Conclusion The toxicity of P. alkekengi fruit extract is concentrated in the non-polysaccharide 5–10 kDa fraction, with GS being the main contributor to the toxicity in this fraction. Membrane-based separation technology to remove this fraction can enhance the safety of the extract. This study provides a framework for the safety evaluation and optimization of traditional medicinal plants.