Eupatilin treatment inhibits transforming growth factor beta-induced endometrial fibrosis in vitro.

OBJECTIVE: Endometrial fibrosis, the primary pathological feature of intrauterine adhesion, may lead to disruption of endometrial tissue structure, menstrual abnormalities, infertility, and recurrent pregnancy loss. At present, no ideal therapeutic strategy exists for this fibrotic disease. Eupatilin, a major pharmacologically active flavone from Artemisia, has been previously reported to act as a potent inducer of dedifferentiation of fibrotic tissue in the liver and lung. However, the effects of eupatilin on endometrial fibrosis have not yet been investigated. In this study, we present the first report on the impact of eupatilin treatment on transforming growth factor beta (TGF-ß)-induced endometrial fibrosis. METHODS: The efficacy of eupatilin on TGF-ß-induced endometrial fibrosis was assessed by examining changes in morphology and the expression levels of fibrosis markers using immunofluorescence staining and quantitative real-time reverse-transcription polymerase chain reaction. RESULTS: Eupatilin treatment significantly reduced the fibrotic activity of TGF-ß-induced endometrial fibrosis in Ishikawa cells, which displayed more circular shapes and formed more colonies. Additionally, the effects of eupatilin on fibrotic markers including alpha-smooth muscle actin, hypoxia-inducible factor 1 alpha, collagen type I alpha 1 chain, and matrix metalloproteinase-2, were evaluated in TGF-ß-induced endometrial fibrosis. The expression of these markers was highly upregulated by TGF-ß pretreatment and recovered to the levels of control cells in response to eupatilin treatment. CONCLUSION: Our findings suggest that suppression of TGF-ß-induced signaling by eupatilin might be an effective therapeutic strategy for the treatment of endometrial fibrosis.

Synergistic effect of melatonin and ghrelin in preventing cisplatin-induced ovarian damage via regulation of FOXO3a phosphorylation and binding to the p27Kip1 promoter in primordial follicles.

Premature ovarian failure during chemotherapy is a serious problem for young women with cancer. To preserve the fertility of these patients, approaches to prevent chemotherapy-induced ovarian failure are needed. In a previous study, we reported that melatonin treatment prevents the depletion of the dormant follicle pool via repression of the simultaneous activation of dormant primordial follicles by cisplatin. However, melatonin's protective effect was only partial and thus insufficient. In this study, we found that the hormone ghrelin enhances the protective effect of melatonin against cisplatin-induced ovarian failure in mouse model. Co-administration of melatonin and ghrelin more effectively prevented cisplatin-induced follicle disruption. Simultaneous treatment with melatonin and ghrelin almost restored the number of primordial follicles and the corpus luteum in cisplatin-treated ovaries, compared with single administration. We found melatonin and ghrelin receptors on the cell membrane of premature oocytes of primordial follicles. In addition, melatonin and ghrelin co-administration inhibited the cisplatin-induced phosphorylation of PTEN and FOXO3a that induces cytoplasmic translocation of FOXO3a. Inhibition of FOXO3a phosphorylation by melatonin and ghrelin increased the binding affinity of FOXO3a for the p27Kip1 promoter in primordial follicles. Co-administration of melatonin and ghrelin in cisplatin-treated ovaries restored the expression of p27Kip1 , which is critical for retention of the dormant status of primordial follicles. In conclusion, these findings suggest that melatonin and ghrelin co-administration is suitable for use as a fertoprotective adjuvant therapy during cisplatin chemotherapy in young female cancer patients.

Antitumor activity of Soamsan, a traditional Korean medicine, via suppressing angiogenesis and growth factor transcription.

Antiangiogenic and antitumor activities of Soamsan known as an anticancer remedy in traditional Korean medicine were examined. In contrast to the normal branching of vascular vessels in chorioallantoic membrane (CAM), blood vessels in CAM treated with Soamsan (50 microg per egg) were run parallel to each other with less branching. Oral administration of Soamsan (20 mg/kg per day) for 4 weeks significantly inhibited the rat corneal neovascularization induced by suture, and the length of blood vessels in Soamsan-treated rat cornea was conspicuously low compared to control. When HT1080 cells, human fibrosarcoma, were treated with 2.18 mg/ml of Soamsan up to 24 h, mRNA transcription of VEGF, TGF-beta and bFGF genes was dramatically reduced in a time-dependent manner. Soamsan showed a prolongation of life span and a reduction of tumor volume in CT-26 cell (colon adenocarcinoma)-bearing mice. These results suggest that antitumor activity of Soamsan may be mediated, at least in part, by antiangiogenic mechanism.