Abstract
Dioscorea nipponica rhizoma (DNR) is commonly used for the cure of hyperthyroidism resulting from Graves’ disease (GD) or thyroid nodules. However, its therapeutic mechanism remains unclear. This study aimed to utilize network pharmacology integrated molecular docking and experimental verification to reveal the potential pharmacological mechanism of DNR against GD. First, the active componds of DNR were collected from the HERB database and a literature search was conducted. Then, according to multisource database, the predicted genes of DNR and GD were collected to generate networks. The analysis of protein–protein interaction and GO enrichment and KEGG pathway were employed to discover main mechanisms associated with therapeutic targets. Moreover, molecular docking simulation was applied in order to verify the interactions between the drug and target. Finally, our experiments validated the ameliorated effects of diosgenin, the main component of DNR, in terms of phosphorylation deactivation in IGF-1R, which in turn inhibited the phosphorylation and activation of PI3K-AKT and Rap1-MEK signaling pathways, promoting cell apoptosis and GD remission. Our present study provided a foundation for further investigation of the in-depth mechanisms of diosgenin in GD and will provide new scientific evidence for clinical application.
Highlights
Graves’ disease (GD) is an organ-specific autoimmune disease featured by hyperthyroidism, diffuse goiter and thyroid-associated ophthalmopathy (Bahn et al, 2011)
To further elucidate the potential pharmacological mechanism of Dioscorea nipponica rhizoma (DNR) against GD, we put common targets on DAVID 6.8 (Huang da et al, 2009) to perform GO biological process (BP), molecular function (MF), cell component (CC) and KEGG pathway analysis (Shi et al, 2017) The items with correction p ≤ 0.01, the top ten pathways with the most enriched targets were selected to visualize the data by bioinformatics
We found that diosgenin (Mu et al, 2012) promoted apoptosis of human primary thyroid cells under the action of IGF-1 through the caspase signaling pathway, but its specific mechanism is not clear
Summary
Graves’ disease (GD) is an organ-specific autoimmune disease featured by hyperthyroidism, diffuse goiter and thyroid-associated ophthalmopathy (Bahn et al, 2011). The primary role of currently used drugs for GD is to Mechanisms of DNR Against Graves’ Disease inhibit thyroid hormones synthesis by interfering with thyroid peroxidase expression rather than promoting apoptosis or inhibiting excessive proliferation of thyrocytes (Cooper, 2005). These antithyroid drugs cannot effectively alleviate goiter, resulting in a heavy financial burden and mental stress on GD patients with large goiters. Proapoptotic and antiproliferative approaches might be potential therapies for the treatment of GD goiter
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