Rehmannia glutinosa nanovesicles protect cardiomyoblasts from oxidative injury

Aim: Oxidative stress is a key driver of cardiovascular disease, underscoring the need for safe and effective antioxidant therapies. This study aims to evaluate the cardioprotective potential of plant-derived nanovesicles (PDNVs) derived from Panax ginseng (Gin) and Rehmannia glutinosa (Glu) against hydrogen peroxide (H₂O₂)-induced oxidative injury in cardiac cells. Methods: PDNVs were isolated from medicinal plants via differential ultracentrifugation and characterized for morphology, diameter, stability, and cellular uptake. The antioxidant and cytoprotective effects were assessed in H₂O₂-injured cardiomyoblasts through cell viability, 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·) radical scavenging, intracellular reactive oxygen species (ROS) and mitochondrial superoxide detection, and antioxidant enzyme (superoxide dismutase, SOD; glutathione peroxidase, GPx) activity assays. The composition of the PDNVs was determined through Coomassie Brilliant Blue staining for proteins, agarose gel electrophoresis for nucleic acids, and liquid chromatography-mass spectrometry system (LC-MS) for bioactive monomers. Results: Gin-PDNVs and Glu-PDNVs significantly enhanced cardiomyoblast viability under oxidative stress. Glu-PDNVs demonstrated superior efficacy at lower concentrations, with stronger ROS scavenging capacity. Compositional analysis revealed that Glu-PDNVs carry proteins, nucleic acids, and antioxidant herbal compounds such as catalpol, rehmannioside D, and acteoside. Glu-PDNVs also dose-dependently scavenged DPPH· radicals, reduced mitochondrial superoxide accumulation, and significantly restored the H₂O₂-induced suppression of SOD and GPx activities. Conclusion: This study provides the first evidence that Glu-PDNVs exert potent cardioprotection by regulating ROS and superoxide homeostasis, positioning them as a promising natural nanotherapeutic platform with translational potential.