article · Journal of Biochemical and Molecular Toxicology
Uterine leiomyomas, commonly known as fibroids, are prevalent benign tumours associated with significant medical burdens and a shortage of uterus-preserving treatments. This research evaluates the therapeutic potential of fisetin, a natural dietary flavonoid, using a rat model of fibroids induced by monosodium glutamate. Treatment with fisetin led to a marked reduction in elevated levels of estradiol and progesterone. It also suppressed key inflammatory markers, including HMGB1, TNF-alpha, and IL-1beta, alongside profibrotic factors such as TGF-beta1 and alpha-SMA. Furthermore, fisetin administration inhibited sphingosine-1-phosphate signalling and improved uterine tissue structure by reducing fibrotic remodelling. These biological changes indicate that fisetin works across connected inflammatory, fibrotic, and signalling pathways, demonstrating potential as a conservative pharmacological intervention for uterine fibroids.
Uterine fibroids affect many women globally, frequently causing severe symptoms and impairing fertility. Current clinical options often require invasive surgery or hysterectomy. Discovering natural compounds that reverse fibroid growth, lower excess hormone levels, and reduce fibrotic tissue without surgical removal offers a potential pathway toward developing non-invasive therapies that preserve fertility.
This research is at an early, preclinical stage, having been evaluated exclusively in an animal model. If supported by further pharmacokinetic, safety, and clinical studies, fisetin could interest pharmaceutical or nutraceutical developers seeking non-surgical, uterus-preserving therapies for uterine leiomyomas. However, substantial clinical testing is required before practical medical application is realised.
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Uterine leiomyomas (UL) represent one of the most prevalent gynecological benign tumors with a considerable global medical and economic burden. Effective therapeutic strategies that preserve the uterus and maintain fertility are still lacking. Fisetin (FIS), a naturally occurring dietary flavonoid, exhibits antitumor, anti-inflammatory, and antifibrotic properties, yet its therapeutic potential in UL remains incompletely defined. This study investigated the therapeutic effects of fisetin on UL and the possible underlying mechanisms. UL was experimentally induced in adult female rats by monosodium glutamate (MSG), and animals were assigned to Control, FIS, UL, and UL + FIS groups. Blood and tissue samples were subjected to hormonal, biochemical, histopathological, and immunohistochemical assessments. Serum estradiol, progesterone, and S1P levels were measured using ELISA, while qPCR quantified the expression of key signaling molecules, including SphK1, TGF-β1, HMGB1, TNF-α, and IL-1β. Immunohistochemistry assessed TGF-β1 and α-SMA expressions, and histopathology (H&E and Masson's Trichrome stains) evaluated tissue architecture and fibrosis. The results showed that fisetin administration significantly reduced the elevated sex hormones, inhibited S1P signaling, and suppressed proinflammatory mediators (HMGB1, TNF-α, IL-1β) and profibrotic mediators (TGF-β1, α-SMA). Histopathological evaluation confirmed decreased fibrotic remodeling and improved tissue architecture. Overall, these results suggest that fisetin's effect may involve coordinated modulation of the S1P/SphK1, TGF-β, and HMGB1 axes, highlighting its potential as a novel uterus-preserving therapeutic agent for UL.
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DOI: 10.1002/jbt.71105
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