Integrate metabolomics strategy and target prediction to reveal the ameliorate effect of four typical ‘cold’ property herbs on hyperthyroidism rats

The 'cold' property herbs are commonly applied in heat syndrome. Unfortunately, the underlying mechanisms of the 'cold' property herbs on heat syndrome has not been investigated.The study aimed to probe the activities of the four typical 'cold' property herbs on hyperthyroidism.Firstly, the four typical 'heat' property herbs were set as contrasting experiment. Then. the physical sign, thyroid function and metabolism profile (multivariate statistical analysis) were assessing the difference between the four typical 'cod' property herbs and the four typical 'heat' property herbs. H&E staining were used to confirmed the influence of the typical 'cold' property herbs on hyperthyroidism. A metabolomics approach combine with network pharmacology were explored the effected mechanism of the typical 'cold' property herbs on hyperthyroidism. the gene expression of UCP-1 was detected by RT-PCR. The metabolites pathway and target-associated metabolites were verified Na+/K+-ATP enzyme and GSH, as well IL6, IL17, MAPK and PPAR-γ, which detected by commercial kits and Western blot.It is proved that the four typical 'cold' property herbs effectively ameliorate the physical sign, thyroid function and metabolism profile in hyperthyroidism rats, but the four typical 'heat' property herbs showed no benefit. Moreover, the four typical 'cold' property herbs regulated energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, thyroid hormone synthesis, arachidonic acid metabolism and linoleic acid metabolism and the inflammation mediated by inflammatory factor (IL6, IL17), Ca2+ and MAPK signaling pathway. And the levels of UCP-1, Na+/K+-ATP enzyme, GSH, and the targets protein of IL6, IL17, MAPK and PPAR-γ were ameliorated by the four typical 'cold' property herbs.The four typical 'cold' property herbs could alleviate hyperthyroidism by ameliorate thyroid hormone synthesis, restraining inflammation and oxidative stress via regulating energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, arachidonic acid metabolism and linoleic acid metabolism and Ca 2+/MAPK signaling pathway, which might be a useful strategy for treating hyperthyroidism.