Fufang Meidengmu (FFMDM) is an ethnic herbal medicine form Yunnan province of China, which is often used for the treatment of uterine leiomyoma (UL). Combined Gancao (Glycyrrhiza uralensis Fisch.) and Haizao (Sargassum pallidum (Turn.) C.Ag) in FFMDM represent an herbal pair in the so-called "eighteen antagonistic medicaments" according to traditional Chinese medicine. In this study, we explored the prevention and treatment effects of FFMDM component compatibility on UL in mice. Female Kunming mice were injected for different periods of time with different concentrations of estradiol benzoate (EB) to investigate a feasible method to establish a mice model of UL. Treatment with 0.3mg/kg EB for 15 days was found to be the optimal condition for UL mice models. We then investigate the role of Gancao and Haizao in FFMDM, and explored the underlying mechanism of action of UL mice. Our findings suggested that Gancao and Haizao exerted the favorable effects. In addition, FFMDM is effective in the treatment of UL, and its mechanism was associated with the estrogen (ER) and progesterone receptors (PR).

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