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. 2016 Aug 9;7(32):51699-51712.
doi: 10.18632/oncotarget.10329.

Thyroid hormone synthesis: a potential target of a Chinese herbal formula Haizao Yuhu Decoction acting on iodine-deficient goiter

Yanqiong Zhang  1 , Yuting Li  1 , Xia Mao  1 , Chen Yan  1 , Xiaodong Guo  2 , Qiuyan Guo  1 , Zhenli Liu  3 , Zhiqian Song  3 , Na Lin  1
Affiliations

Thyroid hormone synthesis: a potential target of a Chinese herbal formula Haizao Yuhu Decoction acting on iodine-deficient goiter

Yanqiong Zhang et al. Oncotarget. .

Abstract

Haizao Yuhu Decoction (HYD), a famous multi-component herbal formula, has been widely used to treat various thyroid-related diseases, including iodine-deficient goiter. Herb pair Thallus Sargassi Pallidi (HZ) and Radix Glycyrrhizae (GC), one of the so-called "eighteen antagonistic medicaments", contains in HYD. To explore pharmacological mechanisms of HYD acting on iodine-deficient goiter and to provide evidence for potential roles of herb pair HZ and GC in HYD, our genome-wide microarray detection and network analysis identified a list of goiter-related genes, mainly involved into the alterations in hypothalamus-pituitary-thyroid/gonad/growth axes. Then, the disease genes-drug genes interaction network illustrated the links between HYD regulating genes and goiter-related genes, and identified the candidate targets of HYD acting on goiter. Functionally, these candidate targets were closely correlated with thyroid hormone synthesis. Moreover, the potential regulating genes of herb pair HZ and GC were revealed to be crucial components in the pathway of thyroid hormone synthesis. The prediction results were all verified by following experiments based on goiter rats. Collectively, this integrative study combining microarray gene expression profiling, network analysis and experimental validations offers the convincing evidence that HYD may alleviate iodine-deficient goiter via regulating thyroid hormone synthesis, and explains the necessity of herb pair HZ and GC in HYD. Our work provides a novel and powerful means to clarify the mechanisms of action for multi-component drugs such as herbal formulae in a holistic way, which may improve drug development and applications.

Keywords: Chinese herbal formula; experimental validation; genome-wide microarray; goiter; network pharmacology.

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Conflict of interest statement

The authors do not have any conflicts of interest with the content of the manuscript.

Figures

Figure 1
Figure 1. A schematic diagram of the integrative strategy combining microarray gene expression profiling, network analysis and experimental validations for investigating the pharmacological mechanisms of herbal formula Haizao Yuhu Decoction acting on iodine-deficient goiter
Figure 2
Figure 2. Unsupervised hierarchical clustering analysis (A) and principal component analysis (B) of all dysregulated genes in goiter model and normal control rats. Red represents a high expression while green represents a low expression. M1~M3, three samples in goiter model group; C1~C3, three samples in normal control group
Figure 3
Figure 3. Goiter-related genes are implicated into alterations in hypothalamus-pituitary-thyroid/gonad/growth axes
Blue nodes refer to the downregulated genes in goiter model group compared to normal control group; Red nodes refer to the upregulated genes in goiter model group compared to normal control group.
Figure 4
Figure 4. Involvement of HYD (A) and the herb pair HZ-GC (B) in thyroid hormone synthesis via regulating the corresponding candidate targets
Figure 5
Figure 5. Effect of HYD and the herb pair HZ-GC on severity of iodine-deficient goiter based on propylthiouracil-induced goiter rats
(A) Reduced levels of T3 in sera of goiter rats could be efficiently increased by the administration of HYD at 0.9 g/(kg·day) for 28 days; (B) Reduced levels of T4 in sera of goiter rats could be efficiently increased by the administration of HYD at 0.9 g/(kg·day) for 28 days; (C) Elevated serum levels of TSH in goiter rats were significantly decreased in HYD treatment group; (D) and (E) Weight of thyroid tissues and TBR were respectively increased in the in goiter model group compared to the normal group; After the treatment of HYD, the two parameters were both significantly lower than those in goiter model rats; (F) Histological observations of the thyroid tissues in different groups (H&E staining). Data are represented as the mean ± S.E. ‘*’, ‘**’, and ‘***’, P<0.05, P<0.01, and P<0.001, respectively, comparison with the normal control group. '#' and '##', P<0.05 and P<0.01, respectively, comparison with the model group. '$' and '$$', P<0.05 and P<0.01, respectively, comparison with the HYD group.
Figure 6
Figure 6. Effect of HYD and the herb pair HZ-GC on mRNA expression levels of the corresponding candidate targets according to real-time PCR analysis
Data are represented as the mean ± S.E. ‘*’, ‘**’, and ‘***’, P<0.05, P<0.01, and P<0.001, respectively, comparison with the normal control group. '#' and '##', P<0.05 and P<0.01, respectively, comparison with the model group. '$' and '$$', P<0.05 and P<0.01, respectively, comparison with the HYD group.
Figure 7
Figure 7. Effect of HYD on protein expression levels of the corresponding candidate targets (A) Adcy1; (B) Adcy2; (C) Creb1; (D) Hspa5; (E) Pdia4; (F) Plcb1; (G) Prkca; (H) Prkcb; (I) Tpo according to Western blot analysis
Data are represented as the mean ± S.E. ‘*’, ‘**’, and ‘***’, P<0.05, P<0.01, and P<0.001, respectively, comparison with the normal control group. '#' and '##', P<0.05 and P<0.01, respectively, comparison with the model group.
Figure 8
Figure 8. Effect of herb pair HZ-GC on protein expression levels of the corresponding candidate targets (A) Adcy2; (B) Atp1a2; (C) Gsr; (D) Iyd; (E) Pdia4; (F) Plcb1; (G) Tg; (H) Tpo according to Western blot analysis
Data are represented as the mean ± S.E. ‘*’, ‘**’, and ‘***’, P<0.05, P<0.01, and P<0.001, respectively, comparison with the normal control group. '#' and '##', P<0.05 and P<0.01, respectively, comparison with the model group. '$' and '$$', P<0.05 and P<0.01, respectively, comparison with the HYD group.
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References

    1. Qureshi IA, Khabaz MN, Baig M, Begum B, Abdelrehaman AS, Hussain MB. Histopathological findings in goiter: A review of 624 thyroidectomies. Neuro Endocrinol Lett. 2015;36:48–52. - PubMed
    1. Knobel M. Etiopathology, clinical features, and treatment of diffuse and multinodular nontoxic goiters. J Endocrinol Invest. 2016;39:357–373. doi: 10.1007/s40618-015-0391-7. - DOI - PubMed
    1. Anees M, Anis RA, Yousaf S, Murtaza I, Sultan A, Arslan M, Shahab M. Effect of maternal iodine supplementation on thyroid function and birth outcome in goiter endemic areas. Curr Med Res Opin. 2015;31:667–74. - PubMed
    1. Zhao W, Han C, Shi X, Xiong C, Sun J, Shan Z, Teng W. Prevalence of goiter and thyroid nodules before and after implementation of the universal salt iodization program in mainland China from 1985 to 2014: a systematic review and meta-analysis. PLoS One. 2014;9:e109549. - PMC - PubMed
    1. Han Y, Gao L, Sun N, Zhang J, Zhang W, Zhou X, Zhang H, Zhao J. Effects of Kang-Jia-Wan, a Chinese medicinal herb officinal, on apoptosis induction in goiter of rats. J Ethnopharmacol. 2009;122:533–40. - PubMed

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