Physiological Indicators of Adenosine and Salidroside Regulating the Motor Behavior in a Caenorhabditis elegans Model Via Ador-1 Adenosine Receptor

Aims: Adenosine and salidroside exert both preventive and therapeutic effects on neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. However, the mechanism is unclear. Methodology: N2 wild-type and EG6890 (Ador-1 gene knockout) Caenorhabditis elegans were used as models, and 0.03, 0.3, and 3 mM adenosine and salidroside were applied to systematically evaluate their effects on the nematodes' physiological indicators (including pharyngeal pumping, bending, head swinging, and swimming). The interaction between salidroside and Ador-1 adenosine receptors was further investigated using molecular docking. Results: The results revealed that N2 wild-type treatment with different concentrations of salidroside and adenosine significantly downregulated pharyngeal pumping, bending, head swinging, and swimming. Comparison of the relative motor ability indices of the N2 and EG6890 strains indicated that adenosine modulated the nematodes' motor abilities via adenosine receptors. In addition to regulating motor behavior through adenosine receptors, salidroside may involve other receptors or demonstrate concentration-dependent effects. Molecular docking results revealed that salidroside exhibits a stronger affinity for the Ador-1 receptor compared to adenosine, suggesting that both compounds regulate motor function through this receptor pathway. Conclusion: This study provides a novel experimental foundation for elucidating the neuroprotective mechanisms of salidroside and adenosine as adenosine receptor agonists, as well as for related drug screening.