Integrated gas chromatography‐mass spectrometry and ultra‐high‐performance liquid chromatography‐mass spectrometry renal metabolomics and lipidomics deciphered the metabolic regulation mechanism of Gushudan on kidney‐yang‐deficiency‐syndrome rats

Kidney‐yang‐deficiency‐syndrome is a neuroendocrine disease caused by the dysfunction of the adrenal‐pituitary‐target gland axis. Gushudan is a traditional Chinese medicine prescription with the functions of tonifying the kidney and strengthening bone, and its bone‐strengthening effect has been confirmed by previous anti‐osteoporosis research. However, its kidney‐tonifying mechanism has not been clear so far. In this study, renal metabolomics and lipidomics based on gas chromatography‐mass spectrometry and ultra‐high‐performance liquid chromatography‐high resolution mass spectrometry were integrated to find the metabolic disorders in kidney‐yang‐deficiency‐syndrome rats. Protein precipitation and liquid‐liquid extraction were used to extract metabolome and lipidome from the kidney. Gushudan regulated abnormal levels of amino acids, lipids, purines, and carbohydrates, such as L‐arginine, hypoxanine, stearic acid, and phosphatidylethanolamine (P‐18:1/20:4), which had effects on many metabolic pathways, such as glycerophospholipid metabolism, sphingolipid metabolism, glycine, serine and threonine metabolism and purine metabolism, and so forth. By integrating metabolomics and lipidomics, this study comprehensively revealed the abnormal metabolic activities of amino acids, lipids, and nucleotides in kidney‐yang‐deficiency‐syndrome, and the metabolic regulation mechanism of Gushudan in preventing kidney‐yang‐deficiency‐syndrome, as well as the improvement of Gushudan in maintaining renal cell structure, mitochondrial function, and energy supply, which also provided some new evidence and connotation for “kidney‐bone” axis.