Endometriotic Implants Regress in Rat Models Treated With Puerarin by Decreasing Estradiol Level

Abstract

Phytoestrogens, which have a weak estrogenic effect, bind to estrogen receptors (ERs), thereby competing with estradiol, have an antiestrogenic effect on women of reproductive age with high estrogenic level. Herein, we examined the ability of the phytoestrogen Puerarin to treat endometriosis in rat models of endometriosis. In total, 75 adult, mature female Sprague-Dawley rats in which endometriotic implants were successfully induced by transplanting autologous endometrial tissue to ectopic sites were used in this study. Oral gavage of Puerarin (at doses of 600, 200, or 60 mg/kg per day) or Danazol (80 mg/kg per day) started 4 weeks after implantation. Control model rats received vehicle alone. After administration for 4 weeks, the weight of the ectopic implants, estradiol concentration, as well as ER-α and Aromatase P450 (P450arom) expression in different groups of rat tissues were evaluated after treatment. The endometriotic tissue weight and serum estrogen levels were significantly lower in high, medium, low dose of Puerarin and Danazol treatment groups than that in control group (P < .05 or P < .01). Low-dose Puerarin inhibited P450arom expression and significantly reduced estrogen levels in endometriotic tissue (P < .01). Three doses of Puerarin had no adverse effects on liver, kidney, and ovary, whereas high-dose Puerarin administration caused thinner bone trabecula with distortion and breakage and Danazol administration caused mild or moderate hepatic cell damage. These data demonstrate that Puerarin was able to effectively suppress the growth and development of ectopic endometrium in the rat endometriosis model, even at low doses, suggesting it may be an effective treatment for endometriosis.

Towards the evaluation in an animal disease model: Fluorinated 17β-HSD1 inhibitors showing strong activity towards both the human and the rat enzyme

“…In endometriotic tissue samples of patients with endometriosis, the intracellular E2 concentrations remain higher over E1 throughout the whole menstrual cycle. In the rat endometriosis model, endometrial explants, that are autologously transplanted to ectopic sites outside the uterus, also contain very high levels of E2, about two orders of magnitude higher than in the serum [51]. Yet, at the same time, because of significantly increased intracellular concentration of E2 in endometriotic tissue [50,51], it may also be difficult for the compound to compete with E2, and thus a higher than expected selectivity towards 17ß-HSD1 inhibition is also possible.…”

“…In the rat endometriosis model, endometrial explants, that are autologously transplanted to ectopic sites outside the uterus, also contain very high levels of E2, about two orders of magnitude higher than in the serum [51]. Yet, at the same time, because of significantly increased intracellular concentration of E2 in endometriotic tissue [50,51], it may also be difficult for the compound to compete with E2, and thus a higher than expected selectivity towards 17ß-HSD1 inhibition is also possible. Recently, a more than 100-fold selective (and estrone-derived) 17ß-HSD1 inhibitor has been shown to effectively block the increased E2 synthesis in human endometriotic tissue specimens [12].…”

Novel Medical Treatment Modalities of Endometriosis

“…In a pilot study, three patients with endometriosis and adenomyosis were given a dose of 1000 mg/day valproic acid for 3 months. At the end of the therapy, a complete relief of pain in all cases was detected and one participant's uterine size was reduced 105 . Anti cancer agents can be an option for treatment of endometriosis as a benign disease in the future.…”

Pharmacologic therapies in endometriosis: a systematic review

“…These compounds might thus be expected to have an impact on the development and the severity of endometriosis. However, few studies have investigated the effects of isoflavones on this disease (97,191,192).…”