Mechanism difference of ginseng medicines with different natures on hyperthyroidism

Medicinal nature is a unique index in traditional Chinese medicine (TCM) to measure the efficacy of Chinese medicines. Hyperthyroidism, qi-Yin deficiency syndrome in TCM was regarded as the classic heat syndrome category in Chinese medicine. Moreover, it is extensively employed to evaluate the medicinal nature of herbs within the framework of the 'hot/cold' nature theory. Ginseng, red and black ginseng (GS, RG, and BG, respectively), and ginseng leaves (GL) are qi-tonifying herbs with different medicinal natures and were just right used to examine the underlying mechanisms between the nature of ginseng medicines and their tonifying effect.To examine the different mechanisms between different natures of ginseng medicines and their qi-tonifying action by comparison of their effects on hyperthyroidism and elucidate the nature of BG.The hyperthyroidism model was induced through the oral administration of Euthyrox. Steroids belonging to hypothalamus pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes were determined with an ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method. Furthermore, the biochemical indexes associated with energy metabolism, including the serum cyclic nucleotide system and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways were examined. Additionally, the gut microbiota was subjected to 16 S rDNA sequencing, followed by gas chromatography-mass spectrometry (GC-MS) analysis of short-chain fatty acids (SCFAs).GS, RG, and BG could treat hyperthyroidism rats by regulating the hypothalamus pituitary thyroid (HPT) axis. The RG also had a strong regulatory effect on the HPA and HPG axis. The BG has a regulatory effect on the HPG axis. GL had a strong regulatory effect on HPA, HPG, and HPT axes. GS had the ability to regulate Firmicutes/Bacteroides of the intestinal flora, and GS, RG, and BG ameliorated the decrease of SCFAs induced by hyperthyroidism. According to PCA, BG is similar to GS, indicating a mild-warm nature.The nature of BG was attributable to mild-warm and the GL with cold nature is best for the treatment of hyperthyroidism based on PCA analysis with all the bio-indices. In addition, the mechanism study indicated that the qi-tonifying effects of ginseng medicines are involved in HPT, HPA, and HPG axes to alleviate hyperthyroidism. In addition, the primary indexes reflected different natures of ginseng medicines are cyclic adenosine monophosphate (cAMP)/cyclic guanosine monophosphate (cGMP), AchE, and substance metabolism associated with Na+-K+-ATPase and PI3K/AKT signaling pathways, which are potential biomarkers for evaluation on the natures of qi-tonifying medicines.