Cortex Lycii attenuates night sweat in Yin-deficient rat by downregulating β 2 AR/cAMP signaling: A proteomic approach

Abstract Purpose: To investigate the therapeutic effect of Cortex Lycii on the sweat secretion of YDH rats and its underlying mechanism. Methods: Male SD rats (N=36) were randomly assigned into Control, YDH, and DI groups (N=12 each group). YDH model rats were constructed by oral administration of thyroxin and reserpine. After two-weeks treatment of Cortex Lycii, the pharmacodynamics was assessed then the protein profile was obtained using a tandem mass tag proteomic approach. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis was used for bioinformatics analysis of differential expressed proteins (DEPs), critical DEPs were validated by Western blot. The receptor involved in the Cortex Lycii were confirmed by using β₂AR receptor agonist (isoproterenol)- and M₃R receptor agonist (pilocarpine)-induced sweat secretion in YDH rats. Results: Cortex Lycii attenuates sweat secretion in YDH rats, and down-regulated the expression of AQP₅ and β₂-receptor on paw pads of YDH rats. Proteomics analysis revealed 189 differential proteins between the model and control groups, of which 124 differential proteins were remarkably reversed by Cortex Lycii. The overlapping DEPs in the model and Cortex Lycii groups were mainly enriched in the β₂AR/cAMP pathway. Moreover, Cortex Lycii considerably attenuated the agonistic effect of isoprenaline induced sweat secretion. Conclusion: This study demonstrated the effect of Cortex Lycii on sweat secretion in Yin-deficient rats. The mechanism on the ground may refer to the inhibition of β₂AR/cAMP, followed by the suppression of the downstream PKA/ezrin/CFTR signaling pathway to reduce ion exchange and the inhibition of IP₃/Ca²⁺/AQP₅. The finding may provide new research on the mechanism of night sweats in TCM and their amelioration by Cortex Lycii.