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Abstract Title:

Nobiletin alleviates endometriosis via downregulating NF-κB activity in endometriosis mouse model.

Abstract Source:

Biosci Rep. 2018 Jun 5. Epub 2018 Jun 5. PMID: 29871974

Abstract Author(s):

Xin Wei, Xu Shao

Article Affiliation:

Xin Wei

Abstract:

Nobiletin exhibits protective potential on inflammation and inhibits the activation of transcription factors NF-κB. However, its effects on the progression of endometriosis remain unsettled. This study aimed to explore thealleviation of nobiletin on endometriosis and its mechanism of action. The mouse model of endometriosis was established and administered with nobiletin. The ectopic lesion size was measured and the hotplate test was performed to assess the amelioration of nobiletin on endometriosis. The expression of proliferation and angiogenesis relevant genes including PCNA, VEGF and E-cadherin was measured by immunostaining and the mRNA expression of pro-inflammatory mediators including IL-6, IL-1β, TNF-α, MMP-1 and MMP-3 was measured by RT-PCR. The change of NF-κB activity in endometriotic cells was evaluated by western blotting and confirmed by luciferase assay. Administration of nobiletin significantly reduced lesions size and pain in endometriosis mice.  Nobiletin significantly altered the expression of PCNA, VEGF and E-cadherin in ectopic endometrium, as well as the levels of IL-6, IL-1β, TNF-α, MMP-1 and MMP-3. Nobiletin also showed remarkably impairment on the activation of NF-κB in promoting endometriotic cells, likely targeting on the activity of IκB kinases (IKKs). This study provides the first evidence that nobiletin exert protection on endometriosis via inhibition the activation of NF-κB, specifically on the activity of IκB kinases.

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