Abstract

Background The management of adenomyosis is challenging and limiting. Qiu's Neiyi recipe (Qiu) is a traditional Chinese medicine (TCM) prescription clinically used for endometriosis treatment in China, but the effect and mechanism of Qiu on adenomyosis are undefined. Methods An experimental adenomyosis model was induced in female neonatal ICR mice administrated with tamoxifen. The adenomyosis mice were divided into five groups: high-, middle-, and low-Qiu's group, danazol group, and model group. The mice just administrated with the solvent only (no tamoxifen or drugs) were served as the control group. After 28 days of administration, the body, uterine, spleen, and thymus weights of all mice were examined. Then, the myometrial infiltration and the expression of inflammatory factors were detected by histology examination, ELISA, and qRT-PCR in the uterus. In addition, the MAPK/ERK signaling pathway-related protein expression in adenomyosis mice was detected by immunohistochemical (IHC) staining, qRT-PCR, and western blotting. Results In experimental adenomyosis mice, Qiu treatment improved the symptoms of adenomyosis by reducing the myometrial infiltration and increasing the index of spleen and thymus. The elevated levels of IL-1β, IL-6, and TNF-α in serum and uterus tissues of adenomyosis model mice were also decreased after Qiu treatment. The improvement of Qiu on the adenomyosis was achieved by inhibiting the activated MAPK/ERK signaling pathway, including reducing the mRNA and protein expressions of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 in the uterus tissues. Conclusion Qiu alleviated the inflammatory reaction and uterus histological changes in mice with adenomyosis, and the potential mechanism is through the inhibition of the MAPK/ERK signaling pathway. Qiu may be a promising treatment for adenomyosis.

Highlights

  • Adenomyosis is a common disease occurring in reproductive-aged women

  • Qiu’s Neiyi recipe (Qiu) was designed based on the syndrome typing of traditional Chinese medicine (TCM) and followed the rules for drug synergism and compatibility [8]. e protective roles of Qiu and the active herbal in it for the treatment of adenomyosis have been confirmed clinically [8,9,10, 22, 23]

  • It was found that Qiu could attenuate the development of tamoxifen-induced adenomyosis in mice in a dose-dependent manner, and this may be related to the regulation of inflammatory MAPK signaling

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Summary

Introduction

Adenomyosis is a common disease occurring in reproductive-aged women. Adenomyosis is histologically defined by the invasion of endometrial stroma and glands deeply into the myometrium [3]. It is associated with the reactive hyperplasia and myometrial hypertrophy induced by chronic inflammatory injuries in the endometrium [4]. Surgery is a surgical treatment commonly used for adenomyosis, accompanied by risks of surgical trauma and infertility [5]. The effect and precise molecular mechanism of Qiu on adenomyosis therapy remain unclear and need to be investigated

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