Sargassum species combined with Glycyrrhiza uralensis is a famous herbal pair in traditional Chinese medicine, as one of the so-called "eighteen antagonistic medicaments." In the Chinese Pharmacopoeia, two different species of Sargassum, Sargassum pallidum and Sargassum fusiforme, are recorded but they are not clearly differentiated in clinical use. In this study, we aimed to determine whether the two species of Sargassum could result in different effects when combined with G. uralensis in Haizao Yuhu Decoction (HYD), which is used for treating thyroid-related diseases, especially goiter. HYD containing S. pallidum or S. fusiforme was administered to rats with propylthiouracil-induced goiter. After 4 weeks, pathological changes in the thyroid tissue and the relative thyroid weight indicated that HYD containing S. pallidum or S. fusiforme protected thyroid tissues from propylthiouracil damage. Neither species increased the propylthiouracil-induced decrease in serum levels of thyroid hormones. However, there were some differences in their actions, and only HYD containing S. fusiforme abated the propylthiouracil-induced elevation of serum thyroid-stimulating hormone levels and activated thyroglobulin mRNA expression.

In traditional Chinese medicine, Glycyrrhiza and Sargassum are one pair of the "18 incompatible medicaments," which in theory cannot be used together. However, since ancient times, many reports have described using compounds containing both Glycyrrhiza and Sargassum to treat diseases. Haizao Yuhu Decoction (HYD), which contains both ingredients, is mainly used to treat goiter. Chinese Pharmacopoeia officially recorded three varieties of Glycyrrhiza: Glycyrrhiza uralensis, Glycyrrhiza inflata, and Glycyrrhiza glabra. These three varieties have certain differences in chemical composition and pharmacological effects. The purpose of the present study was to investigate whether the HYD containing different varieties of Glycyrrhiza and Sargassum had different therapeutic effects in rats with goiter and to elucidate the underlying mechanism of any difference. In this study, propylthiouracil (PTU) was used to replicate the goiter model, then HYDs containing different varieties of Glycyrrhiza were used for treatment for four weeks, and then the relevant indicators were tested. The results demonstrated that HYD had antigoiter effects, alleviated the pathological changes in the thyroid tissue, and restored the abnormal serum levels of hormones related to thyroid function induced by PTU. HYD containing Glycyrrhiza uralensis had the best therapeutic effect in rats with PTU-induced goiter. The antigoiter effect of HYD may function through the hypothalamic-pituitary-thyroid (HPT) axis, inhibit the expression of the Tg and NIS genes, and regulate the synthesis of thyroid hormones, thereby reducing the excessive stimulation of TSH in thyroid cells. In addition, HYD also prevented goiter by promoting thyroid cell apoptosis and inhibiting the ERK/RSK1 pathway of cell proliferation. In conclusion, three types of HYD had different therapeutic effects in rats with goiter, which might be caused by the compatibility of different varieties of Glycyrrhiza and Sargassum.