Shenrong Wuzi Pill affects the pathway of thyroid hormone synthesis by targeting thyrotropin-releasing hormone receptor and altering cAMP production

Shenrong Wuzi Pill (SWP) is a traditional Chinese medicine used for hypothyroidism treatment. It contains fourteen herbs. However, little is known about the active components and the mechanism of SWP. To reveal the chemical components and drug targets and to systematically dissect the underlying mechanism of SWP as a treatment for hypothyroidism, a network pharmacology approach was used in this study. Four networks were set up, including a hypothyroidism gene network, a pathway of hypothyroidism network, a compound-compound target network, and a compound-compound target-hypothyroidism gene network. Moreover, further analysis focused on overlapping genes between compound targets and hypothyroidism genes. As a result, 14 compounds, 29 overlapping genes and 3 pathways were selected. It was found that SWP and lauric acid from Plantago asiatica L., both upregulated thyrotropin-releasing hormone receptor (TRHR) at mRNA and protein levels in NG108-15 cells. Additionally, lauric acid and atropine from Lycium barbarum L. both upregulated growth hormone secretagogue receptor (GHSR) at the mRNA level; adenine from Poria cocos (Schw.) Wolf. and 17 alpha-estradiol from Cornu Cervi Pantotrichum upregulated adenylyl cyclase 10 (ADCY10) and follicle -stimulating hormone receptor (FSHR) at mRNA levels, respectively. However, mRNA levels of GHSR, ADCY10 and FSHR were not affected significantly by SWP treatment. Furthermore, SWP, lauric acid, adenine and atropine all upregulated cellular cyclic adenosine monophosphate (cAMP) concentration, which is important for triiodothyronine (T3) and thyroxine (T4) production. Taken together, it was concluded SWP affects the pathway of thyroid hormone synthesis by targeting TRHR and altering cAMP production.