Metabolomics analysis reveals that Qingxiangyin improves central precocious puberty through 13S-hydroxyoctadecadienoic acid mediated linoleic acid metabolic for regulating the PPAR pathways

Abstract

The occurrence of central precocious puberty (CPP) among children which is induced by untimely activation of the hypothalamic-pituitary-gonadal (HPG) axis is increasing gradually. Traditional Chinese Medicine endeavors to eradicate or mitigate the underlying factors and thereby reestablish the balance within the physiological system, Qingxiangyin (QXY) is a Chinese medicine that can effectively improve CPP via balancing Yin and Yang. However, the metabolic regulation mechanism of QXY on CPP is still unclear. Here, we established a CPP mouse model, and carried out Leuprorelin (lep), Qingxiangyin high (QXY-h), middle (QXY-M) and low (QXY-L) treatment. The metabolic profile of hypothalamus was evaluated by LC-MS/MS. The major differentially expressed metabolites (DEMs) between the CPP model and blank group were (S)-Abscisic acid, Methylmalonic acid, 2-Oxo-4-methylthiobutanoic acid. The main metabolites in QXY-h vs model were pyridoxal phosphate, phenylpyruvate and palmitoylcarnitine. There were 14 distinct metabolites in the model vs. QXY-M group, among which 3 were up-regulated and 11 were down-regulated. The principal metabolite was succinic acid, phenylpyruvic acid and 13S‑hydroxy-octanadienoic acid. QXY-L induced alterations in 20 metabolites in CPP, with 5 metabolites up-regulated and 15 metabolites down-regulated. The major metabolites were 13S-hydroxyoctaenodienoic acid, benzoylamine, cyclohexanamine and palmitic acid. QXY-mediated metabolites were involved in “PPAR signaling pathway”, “linoleic acid metabolism”, “Lysine degradation” in CPP. In conclusion, the 13S-hydroxyoctadecadienoic acid mediateed linoleic acid metabolism for regulating the PPAR signaling pathway is the key mechanisms by which QXY affects CPP. Our results provide insights into the study of QXY therapy for CPP.