Fisetin, a Natural Polyphenol, Ameliorates Endometriosis Modulating Mast Cells Derived NLRP-3 Inflammasome Pathway and Oxidative Stress.
Alessia ArangiaYlenia MarinoRoberta FuscoRosalba SiracusaMarika CordaroRamona D'amicoFrancesco MacrìEmanuela RaffoneDaniela ImpellizzeriSalvatore CuzzocreaRosanna Di PaolaPublished in: International journal of molecular sciences (2023)
A chronic, painful, and inflammatory condition known as endometriosis is defined by the extra-uterine development of endometrial tissue. The aim of this study was to evaluate the beneficial effects of fisetin, a naturally occurring polyphenol that is frequently present in a variety of fruits and vegetables. Uterine fragments were injected intraperitoneally to cause endometriosis, and fisetin was given orally every day. At 14 days of treatment, laparotomy was performed, and the endometrial implants and peritoneal fluids were collected for histological, biochemical, and molecular analyses. Rats subjected to endometriosis presented important macroscopic and microscopic changes, increased mast cell (MC) infiltration, and fibrosis. Fisetin treatment reduced endometriotic implant area, diameter, and volumes, as well as histological alterations, neutrophil infiltration, cytokines release, the number of MCs together with the expression of chymase and tryptase, and diminished α smooth muscle actin (α-sma) and transforming growth factor beta (TGF β) expressions. In addition, fisetin was able to reduce markers of oxidative stress as well as nitrotyrosine and Poly ADP ribose expressions and increase apoptosis in endometrial lesions. In conclusion, fisetin could represent a new therapeutic strategy to control endometriosis perhaps by targeting the MC-derived NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway and oxidative stress.
Keyphrases
- oxidative stress
- nlrp inflammasome
- transforming growth factor
- smooth muscle
- dna damage
- ischemia reperfusion injury
- epithelial mesenchymal transition
- endometrial cancer
- induced apoptosis
- poor prognosis
- signaling pathway
- drug induced
- cell death
- cell proliferation
- soft tissue
- combination therapy
- cell cycle arrest
- risk assessment
- human health
- long non coding rna
- heat shock protein