Endometriotic implants regress in rat models treated with puerarin by decreasing estradiol level

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Puerarin treatment in a rat endometriosis model reduced endometriotic implant weight and estradiol levels by decreasing ER-α and P450arom expression without significant adverse effects at low doses.

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This study used 75 adult female Sprague-Dawley rats with endometriotic implants created by transplanting autologous endometrial tissue to ectopic sites, comparing oral puerarin at 600, 200, or 60 mg/kg/day or danazol (80 mg/kg/day) given starting 4 weeks after implantation versus vehicle controls for 4 additional weeks. Treatment with all three puerarin doses and danazol significantly reduced endometriotic implant tissue weight and serum estrogen/estradiol levels, and was associated with decreased ER-α and aromatase (P450arom) expression; low-dose puerarin specifically inhibited P450arom expression and reduced estrogen levels in endometriotic tissue. The paper reports no adverse effects on liver, kidney, and ovary with three puerarin doses, but high-dose puerarin caused bone trabecular thinning/distortion and danazol caused mild to moderate hepatic cell damage. This paper is centrally about endometriosis—testing puerarin’s ability to regress endometriotic implants in a rat endometriosis model via lowering estradiol.

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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.
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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 orP < .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. Similar content being viewed by others

References

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endometriosis

MeSH descriptors

Endometriosis Endometriosis Estradiol Isoflavones Phytoestrogens Animals Endometriosis Estradiol Estradiol Estrogen Receptor alpha Estrogen Receptor alpha Estrogen Receptor beta Estrogen Receptor beta Female Isoflavones Phytoestrogens Random Allocation Rats Rats, Sprague-Dawley

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