Diosgenin From Dioscorea Nipponica Rhizoma Against Graves’ Disease—On Network Pharmacology and Experimental Evaluation
Authors: Jingxin Xin
Wencong Cheng
Juan Chen
Xinhuan Zhang
Shanshan Shao
Yongbing Yu
Journal: Frontiers in Pharmacology (2022)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: IGF-1R; apoptosis; dioscorea nipponica rhizoma; diosgenin; graves’ disease
Affiliations: Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China., Department of Endocrinology, The Second Affiliated Hispital of Shandong First Medical University, Taian, China.

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. 

Retracted: No

PubPeer comments:
 Could the authors comment on whose idea it was to add the references to Chao Zhao s work on processing waste foliage to maximise the production of biofuel? How are they relevant to increasing the yield of phytochemicals?  In order to get diosgenin with better quality and purity from botanical sources, various techniques including elicitation, genetic transformations and bioconversions were employed (Nazir et al., 2021) (Chao et al., 2017; Qiao et al., 2018). - Chao, Zhao., Yan, Cao., and Zhongqing, Ma. (2017). **Optimization of Liquid Ammonia Pretreatment Conditions for Maximizing Sugar Release from Giant Reed** (*Arundo donax* L.). Biomass and Bioenergy 98, 61u201369. doi:10.1016 j.biombioe.2017.01.001 *[should be **Zhao et al**]* - Qiao, X., Zhao, C., and Qianjun, S. (2018). **Structural Characterization of Corn Stover Lignin after Hydrogen Peroxide Presoaking Prior to Ammonia Fiber Expansion Pretreatment**. Energy and Fuels 32 (5), 6022u20136030. doi:10.1021 acs.energyfuels.8b00951  ... the water contents in diosgenin could be assayed with high accuracy using the mathematical model of near-infrared spectroscopy technology (M. Zhang et al., 2019). - Zhang, M., Zhao, C., Zhao, C., Shao, Q., Yang, Z., Zhang, X., et al. (2019). **Determination of Water Content in Corn stover Silage Using Near-Infrared Spectroscopy**. Int. J. Agric. Biol. Eng. 12 (6), 143u2013148. doi:10.25165 j.ijabe.20191206.4914 And again:  For the past few years, the biological activities of diosgenin has drawn much attention by studied in vivo and in vitro (Leger et al., 2004; J.; Liagre et al., 2004; M. J.; Liu et al., 2005; Liagre et al., 2004; Srinivasan et al., 2009; Li et al., 2010; Ru et al., 2014; **Chao et al., 2017; Qiao et al., 2018;** Kessler et al., 2019; N.; Wang et al., 2019; M. Zhang et al., 2019; Mohamadi-Zarch et al., 2020). This misinterpretation of Zhao s work is [remarkably widespread] . ,