Transcriptomic Profiling of Sea Buckthorn (Hippophae rhamnoides L.) Juice Intervention in 3D hAESC Spheroids: Implications for Cellular Plasticity and Tissue Regeneration

Background/Objective: Sea buckthorn contains an exceptionally rich profile of bioactive nutrients and metabolites, with established systemic therapeutic benefits across diverse pathological models. However, comprehensive data bridging these systemic outcomes with specific tissue responses are still lacking. This descriptive transcriptomic study establishes a predictive framework to guide the future application of sea buckthorn and its isolated derivatives in targeted preventive and therapeutic strategies. Methods: We utilized a 3D spheroid culture of normal human amniotic epithelial stem cells (hAESCs) to evaluate the bioactivity effects of sea buckthorn juice (SBJ) treatment. Results: Microarray analysis validated spheroid structural growth by revealing the upregulation of key upstream markers of proliferation. This SBJ-induced proliferation was supported by a coordinated upregulation of mitochondrial machinery, including oxidative phosphorylation, mitochondrial RNA processing, the TCA cycle, and mitochondrial membrane organization. Cell type signature analysis revealed that treated cells acquired highly proliferative and active extracellular matrix (ECM) remodeling traits. Furthermore, tissue database mapping showed that the cells shared strong transcriptional similarity with human embryo and Wharton’s jelly proliferative states. Muscle-type signatures, including cardiomyocyte, myoblast, and smooth muscle lineages, were consistently enriched. Conclusions: Overall, these findings provide a transcriptomic signature-based predictive model for the biological effects of SBJ. Based on gene ontology and tissue-specific enrichment profiles, our data offer hypothesis-generating predictions suggesting a potential role for SBJ in supporting cellular regeneration via stem cell proliferation. Furthermore, tissue-specific analysis indicates a putative capacity to modulate smooth muscle integrity, inferred from transcriptomic similarities with muscle-type gene signatures. While pure extracted compounds demonstrate beneficial effects, evaluating the whole SBJ matrix provides a broader understanding of its full, unique profile of bioactive properties. These in vitro findings highlight the potential value of the complete juice matrix, forming a predictive baseline for future in vivo and clinical evaluations.