The Anti-Endometriotic Effect of Cyperi Rhizoma Extract, Inhibiting Cell Adhesion and the Expression of Pain-Related Factors through Akt and NF-kB Pathways.

Ji-Hye Ahn,Eun-Sol Kang,Jung-Hye Choi,Dae Sik Jang,Yoon-Jin Cho,Jun-Myeong Choi,Jae-Hyeon Yoo

doi:10.3390/medicina58030335

Ji-Hye Ahn, Eun-Sol Kang + Show 5 more

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https://doi.org/10.3390/medicina58030335

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Abstract

Rhizomes of Cyperus rotundus have been widely used as a traditional medicine in Asia for the treatment of gynecological diseases. However, there is no scientific evidence demonstrating the effect of C. rotundus rhizomes on endometriosis, which is characterized by the adhesion of endometrial tissues outside the uterus, resulting in chronic and severe pelvic pain. The aim of this study was to investigate the effects of Cyperi rhizoma extract (CRE) on cell adhesion and the expression of pain-related factors (neurotrophins) in endometriotic cells, and to elucidate the underlying molecular mechanisms. CRE inhibited the adhesion of human endometriotic 12Z cells to peritoneal mesothelial Met5A cells using by adhesion assays. The mRNA expression of adhesion molecules [P-cadherin and matrix metalloproteinase (MMP)-2] was downregulated by CRE treatment. In addition, CRE significantly inhibited the mRNA expression of neurotrophins (BDNF, NGF, NT-3 and NT-4/5) in 12Z cells. Moreover, Akt overexpression markedly neutralized the inhibition of cell adhesion by CRE and expression of neurotrophins in 12Z cells. Furthermore, it was found that CRE suppressed NF-kB activation through the Akt pathway. These data suggest that CRE exerts anti-endometriotic activities by the inhibition of cell adhesion and neurotrophin expression, through the negative regulation of the Akt and NF-kB pathways in endometriotic cells.

Highlights

Endometriosis is a chronic gynecological disease causing chronic pelvic pain, dysmenorrhea, dyspareunia and infertility [1]
Since the implantation of endometrial fragments at the peritoneum, which is covered by a mesothelial cell layer, is a key step in the establishment of endometriosis [24,26], we investigated the effect of Cyperi rhizoma extract (CRE) on the adhesion of endometriotic cells to mesothelial cells
We investigated the expression of P-cadherin and matrix metalloproteinase (MMP)-2, which have been well known as potent determinants in peritoneal adhesion formation [5], after treatment with CRE in endometriotic 12Z cells

Summary

Introduction

Endometriosis is a chronic gynecological disease causing chronic pelvic pain, dysmenorrhea, dyspareunia and infertility [1]. It is characterized by the presence and growth of endometrial tissue outside the uterus in the peritoneal cavity. It affects approximately 6–10% of women of reproductive age and 30–50% of women with chronic pelvic pain [2]. Emerging studies have demonstrated that neurotrophins, as a family of nerve growth factors, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5), are observed in endometriotic lesions, resulting in pelvic pain in endometriosis via neurogenic inflammation [10,11]

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