Study on the substance basis of the efficacy of eucommiae cortex before and after salt processing for the treatment of kidney-yang deficiency syndrome based on the spectrum-effect relationship

Kidney-Yang deficiency syndrome (KYDS) is one of the common diseases of the elderly and closely related to the ageing of the body, it has a major impact on the quality of life of the patient. Eucommiae Cortex (EC) is the dried bark of Eucommia ulmoides Oliv. Which has the effect of tonifying the liver and kidneys, strengthening the muscles and bones. In Traditional Chinese Medicine clinics, EC is commonly used in the treatment of KYDS, but the material basis for the improvement of its efficacy in treating KYDS after salt processing remains unclear.This study aimed to find the main active ingredients that could improve the treatment of KYDS efficacy of EC after salt processing.Firstly, the fingerprints of raw and salt-processed EC were established to determine the common components by using HPLC, and then an experimental study on the treatment of KYDS efficacy was carried out to compare the difference in the efficacy between raw and salt-processed EC. Thirdly, the spectrum-effect relationship of chemical components and pharmacodynamic indexes was established by using Grey Relational Analysis and Entropy Method. Finally, the network pharmacology and molecular docking technique was used to verify the kidney tonifying effect of the active ingredients of EC.According to the results of the analysis of hormonal index levels on the hypothalamic-pituitary-target gland axis and the extent of renal lesions, the therapeutic effect of EC on KYDS was mainly reflected in the regulation of the Adrenocorticotropic hormone, Corticosterone in the hypothalamic-pituitary-adrenal axis and Tri-iodothyronine, Tetra-iodothyronine in the hypothalamic-pituitary-thyroid axis, moreover the therapeutic effect of salt-processed EC was stronger than that of raw EC. The pharmacologically active ingredients that improved its treatment of KYDS efficacy after salt processing were peak 1 (geniposidic acid), peak 2 (chlorogenic acid), peak 5 (geniposide), peak 6 (genipin), peak 7 (pinoresinol diglucoside) and peak 11 (hyperoside). Meanwhile, the results of network pharmacology and molecular docking showed that the 6 active ingredients could exert kidney tonic effects through multiple signaling pathways by acting on core targets such as AKT1 and PTGS2.As far as we known, this was the first time to establish and compare the spectrum-effect relationship between raw and salt-processed EC, which laid the foundation for the pharmacokinetics studies of EC and provided a reference for future EC studies.