Thyroid hormone synthesis: a potential target of a Chinese herbal formula Haizao Yuhu Decoction acting on iodine-deficient goiter
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Yanqiong Zhang1,*, Yuting Li1,*, Xia Mao1, Chen Yan1, Xiaodong Guo2, Qiuyan Guo1, Zhenli Liu3, Zhiqian Song3, Na Lin1
1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
2302 Hospital of PLA, Beijing 100039, China
3Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China
*These authors have contributed equally to this work
Na Lin, email: [email protected]
Yanqiong Zhang, email: [email protected]
Keywords: Chinese herbal formula, goiter, genome-wide microarray, network pharmacology, experimental validation
Received: February 12, 2016 Accepted: June 17, 2016 Published: June 30, 2016
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.
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