Whole genome circRNA profiling of Withania somnifera in human neuroblastoma SK-N-SH cells

Objectives Defined by their unique covalently closed loop, circular RNAs (circRNAs) are a specific class of noncoding RNAs known for their stability and resilience against degradation. They act as microRNA sponges, transcriptional regulators, and modulators of protein interactions. Withania somnifera (WS), a prominent member of the Solanaceae family, is renowned for its anti-oxidative and neuroprotective properties. Although circRNAs are recognized as critical regulators in neurological disorders, their putative roles in eliciting the health-beneficial effects of WS, also known as Ashwagandha, are still unexplored. Methods This study investigates WS-modulated global circRNA expression profiles in the SK-N-SH human neuroblastoma cell line, a widely used model for brain-related diseases. We conducted whole genome circRNA profiling using sequencing to identify differentially expressed circRNAs upon WS treatment. Results A total of 26,489 circRNAs were detected, out of which 1,515 were novel. Dose-dependent and temporal differential gene expression analysis found 26 upregulated and 20 downregulated circRNAs which were linked to pathways relevant to neuroinflammation, synaptic plasticity and neuronal survival through functional and pathway enrichment analysis. Conclusions This study sheds light on the regulatory roles of circRNAs in WS’s therapeutic effects, suggesting that modulating circRNA expression may be a key mechanism by which it exerts its benefits. These findings open new avenues for WS-based therapeutic strategies for brain-related diseases, thereby highlighting the therapeutic utility of circRNAs in neurological contexts.