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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Integrative and Regenerative Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1496136

Ziziphus jujube promotes fertility and pregnancy outcomes in Rat model of uterine adhesionsUterine adhesions rat model

Provisionally accepted
Fereshteh Asgharzadeh Fereshteh Asgharzadeh 1*Mahsa Attarian Mahsa Attarian 1Majid Khazaei Majid Khazaei 1Abdulridha Mohammed Al-Asady Abdulridha Mohammed Al-Asady 2Saeide Mansoori Saeide Mansoori 1Hamideh Naimi Hamideh Naimi 1Moein Eskandari Moein Eskandari 1Azar Khorrami Azar Khorrami 1Seyedeh Elnaz Nazari Seyedeh Elnaz Nazari 1Akram Aminian Akram Aminian 3Marjaneh Farazastanian Marjaneh Farazastanian 1Elaheh Eshtad Elaheh Eshtad 1Amir Avan Amir Avan 1Mikhail Ryzhikov Mikhail Ryzhikov 4Malihe Hasanzadeh Malihe Hasanzadeh 1Seyed Mahdi Hassanian Seyed Mahdi Hassanian 1
  • 1 Mashhad University of Medical Sciences, Mashhad, Iran
  • 2 University of Warith Al-Anbiyaa, Karbala, Karbala, Iraq
  • 3 Kerman University of Medical Sciences, Kerman, Kerman, Iran
  • 4 Saint Louis University, Baguio, Philippines

The final, formatted version of the article will be published soon.

    We investigated the therapeutic potency of oral administration of Ziziphus jujube in uterine adhesion (UA) and improving improved pregnancy outcomes. Z. jujube significantly attenuated injury-induced uterine adhesion bands, and uterine shortening, while enhancing endometrial regeneration. This effect was manifested by an increase in the number of glands and uterine endometrial thickness in the rat UA model. Furthermore, Z. jujube ameliorated the IUA-induced inflammation by down-regulating the expression of multiple inflammatory cytokines. It also exhibited antioxidant properties by increasing the activity of antioxidant enzymes in uterine tissue homogenates.Fibrosis in the uterine tissue was notably reduced in Z. jujube-treated animals, as evident evidenced from histological Trichrome staining and decreased expression of pro-fibrotic factors including TGF-β and -SMA in uterine tissue samples. Notably, Z. jujube improved the embryonic development as shown by an increase in the number of total embryos, percent of live embryos, embryo size, and weight. Moreover, Z. jujube improved pregnancy outcomes by increasing the pregnancy rate, and percent of live babies, decreased decreasing the time to conception, and improved improving the growth pattern of babies in the rat model of IUA. Furthermore, Z. jujube effectively suppressed the formation of extra-uterine adhesion bands to internal organs, quantified by reductions in adhesion extent, severity, degree, and total adhesion score. No toxicity-associated morphological changes to the heart, kidney, or liver tissues were observed in the Z. Jujube-treated group. These findings collectively suggest that Z. jujube is a potent safe natural product with anti-inflammatory and anti-fibrotic properties. It warrants consideration as a novel candidate for clinical studies addressing UA in patients.

    Keywords: uterine adhesion, Asherman's syndrome, Ziziphus jujube, Pregnancy, Fertility

    Received: 13 Sep 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Asgharzadeh, Attarian, Khazaei, Al-Asady, Mansoori, Naimi, Eskandari, Khorrami, Nazari, Aminian, Farazastanian, Eshtad, Avan, Ryzhikov, Hasanzadeh and Hassanian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Fereshteh Asgharzadeh, Mashhad University of Medical Sciences, Mashhad, Iran

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.