ReferenceID 1353

Betulinic Acid Inhibits Endometriosis Through Suppression of Estrogen Receptor β Signaling Pathway

Front Endocrinol (Lausanne)

Endometriosis is an inflammatory gynecological disorder characterized by endometrial tissue growth located outside of the uterine cavity in addition to chronic pelvic pain and infertility. In this study, we aim to develo

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Reference Id
1353
Evidence Id
17943
Core Evidence Id
17943
Source Reference Id
2708
Herb2 Reference Id
HBREF003505
Subject Paper Key
HBIN018373_33362719
Pubmed Id
33362719
Doi
10.3389/fendo.2020.604648
Paper Title
Betulinic Acid Inhibits Endometriosis Through Suppression of Estrogen Receptor β Signaling Pathway
Paper Abstract
Endometriosis is an inflammatory gynecological disorder characterized by endometrial tissue growth located outside of the uterine cavity in addition to chronic pelvic pain and infertility. In this study, we aim to develop a potential therapeutic treatment based on the pathogenesis and mechanism of Endometriosis. Our preliminary data showed that the expression of estrogen receptor beta (ERbeta) was significantly increased, while ERalpha was significantly decreased, in endometriotic cells compared to normal endometrial cells. Further investigation showed that betulinic acid (BA) treatment suppressed ERbeta expression through epigenetic modification on the ERbeta promoter, while had no effect on ERalpha expression. In addition, BA treatment suppresses ERbeta target genes, including superoxide dismutase 2 (SOD2), nuclear respiratory factor-1 (NRF1), cyclooxygenase 2 (COX2), and matrix metalloproteinase-1 (MMP1), subsequently increasing oxidative stress, triggering mitochondrial dysfunction, decreasing elevated proinflammatory cytokines, and eventually suppressing endometriotic cell proliferation, mimicking the effect of ERbeta knockdown. On the other hand, gain of ERbeta by lentivirus infection in normal endometrial cells resulted in increased cell proliferation and proinflammatory cytokine release, while BA treatment diminished this effect through ERbeta suppression with subsequent oxidative stress and apoptosis. Our results indicate that ERbeta may be a major driving force for the development of endometriosis, while BA inhibits Endometriosis through specific suppression of the ERbeta signaling pathway. This study provides a novel therapeutic strategy for endometriosis treatment through BA-mediated ERbeta suppression.
Journal
Front Endocrinol (Lausanne)
Publish Year
2020
Experiment Subject
Experiment Type
Cell Experiment
Phenotype Related
Inflammatory Gynecological Disorder; Chronic Pelvic Pain; Endometriosis; Infertility; Mitochondrial Dysfunction
Paper Title Cn
Paper Title En
Betulinic Acid Inhibits Endometriosis Through Suppression of Estrogen Receptor β Signaling Pathway
Bilingual Status
semi_complete