Rhein ameliorates adenomyosis by inhibiting NF-κB and β-Catenin signaling pathway

Feng T, Tingting Feng, Wei S, Shaobin Wei, Yan Wang, Wang Y, Xianyun Fu, Fu X, Shi L, Ling Shi, Qu L, Liyuan Qu, Fan X, Xiaoxue Fan
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2017 · vol. 94 , pp. 231–237 · doi:10.1016/j.biopha.2017.07.089 · PMID:28763746 · W2739634126
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Rhein treatment reduced adenomyosis development by suppressing the NF-κB and β-Catenin signaling pathways.

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Abstract

In the present study, we examined the effects of rhein on pituitary gland implantation-induced adenomyosis, an animal model which mimics human adenomyosis. Oral administration of rhein dose-dependently attenuated hyperplastic and hypertrophic myometrium and improved adenomyosis. The activation of NF-κB and β-catenin signaling pathway was observed in the ectopic endometria. While, rhein dose dependently inhibited the expressions of p-p65, p-AKT and actived Rac1. As Rac1 activation controlled nuclear localization of β-catenin during canonical Wnt signaling, we found that the degradation complex of β-catenin was improved by rhein. In addition, β-catenin nuclear translocation and its downstream genes were markedly suppressed by different doses of rhein. At the same time, decreased activation of epithelial-mesenchymal transition (EMT)-associated proteins including Snail and ZEB1 was detected in rhein-treated mice, indicating that the activation of Wnt signaling pathway was suppressed by rhein. The in vitro study verified a negative regulation of rhein on β-catenin in stromal cells. Stimulation of IL-1β significantly increased the nuclear translocation of β-catenin and improved its target genes expressions. While, rhein remarkably abolished the enhancement in a dose dependent manner. Taken together, our results demonstrated the ability of rhein to inhibit Wnt/β-catenin activation and its potential use in the treatment of adenomyosis and other abnormal activation of β-catenin -associated diseases.

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Condition tags

adenomyosis

MeSH descriptors

Adenomyosis Anthraquinones Anti-Inflammatory Agents beta Catenin NF-kappa B Wnt Signaling Pathway Adenomyosis Adenomyosis Adenomyosis Animals Anthraquinones Anti-Inflammatory Agents beta Catenin Cytokines Cytokines Disease Models, Animal Dose-Response Relationship, Drug Endometrium Endometrium Endometrium

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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