<p>This study evaluated the therapeutic potential of lupeol (LUP), a naturally occurring pentacyclic triterpenoid isolated from <i>Ochrosia elliptica</i> (Labill)., in a rat model of letrozole-induced polycystic ovary syndrome (PCOS). Thirty-five adults female Wistar rats were randomly allocated into five groups: normal control, PCOS model, clomiphene citrate–treated (1&#xa0;mg/kg), and two LUP-treated groups (10 and 20&#xa0;mg/kg). Following PCOS induction, treatments were administered orally for 28 consecutive days. PCOS rats exhibited significantly elevated MDA levels and reduced SOD and CAT activities, indicating severe oxidative stress. Lupeol treatment significantly attenuated lipid peroxidation and enhanced SOD activity. However, the increase in CAT activity did not reach statistical significance compared with the PCOS group. Hormonal analysis showed that both lupeol and clomiphene citrate significantly reduced the high LH and testosterone levels in the PCOS group. Lupeol demonstrated a dose-dependent response, lowering testosterone by 22% at 15&#xa0;mg/kg and 27.9% at 30&#xa0;mg/kg At the molecular level, quantitative real-time PCR analysis showed that PCOS was associated with upregulation of steroiFdogenic genes (<i>Cyp17a1</i> and <i>Hsp3β</i>) and downregulation of the antioxidant regulator Nrf2 and aromatase gene <i>Cyp19a1</i>. These dysregulated gene expression patterns were markedly ameliorated by LUP treatment. Histopathological evaluation revealed multiple enlarged cystic follicles with diminished corpora lutea in PCOS ovaries, whereas LUP administration substantially improved folliculogenesis and luteal development. Immunohistochemical analysis further demonstrated elevated caspase-3 expression in granulosa cells of PCOS ovaries, which was significantly suppressed by LUP in a dose-dependent manner. Collectively, these findings indicate that lupeol exerts potent antioxidant, anti-apoptotic, and hormone-modulatory effects, highlighting its promise as a novel phytotherapeutic candidate for the management of polycystic ovary syndrome.</p>

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Exploring the therapeutic potential of Lupeol isolated from Ochrosia elliptica Labill. leaves in polycystic ovarian syndrome

  • Essam Abdel-Sattar,
  • Marwa A. Ibrahim,
  • Fady Sayed Youssef,
  • Marwa S. Khattab,
  • Riham A. El-Shiekh,
  • Rehab A. Ghandour,
  • Shimaa R. Emam,
  • Heba Hozyen,
  • Marwa Zakaria,
  • Samar M. Mouneir

摘要

This study evaluated the therapeutic potential of lupeol (LUP), a naturally occurring pentacyclic triterpenoid isolated from Ochrosia elliptica (Labill)., in a rat model of letrozole-induced polycystic ovary syndrome (PCOS). Thirty-five adults female Wistar rats were randomly allocated into five groups: normal control, PCOS model, clomiphene citrate–treated (1 mg/kg), and two LUP-treated groups (10 and 20 mg/kg). Following PCOS induction, treatments were administered orally for 28 consecutive days. PCOS rats exhibited significantly elevated MDA levels and reduced SOD and CAT activities, indicating severe oxidative stress. Lupeol treatment significantly attenuated lipid peroxidation and enhanced SOD activity. However, the increase in CAT activity did not reach statistical significance compared with the PCOS group. Hormonal analysis showed that both lupeol and clomiphene citrate significantly reduced the high LH and testosterone levels in the PCOS group. Lupeol demonstrated a dose-dependent response, lowering testosterone by 22% at 15 mg/kg and 27.9% at 30 mg/kg At the molecular level, quantitative real-time PCR analysis showed that PCOS was associated with upregulation of steroiFdogenic genes (Cyp17a1 and Hsp3β) and downregulation of the antioxidant regulator Nrf2 and aromatase gene Cyp19a1. These dysregulated gene expression patterns were markedly ameliorated by LUP treatment. Histopathological evaluation revealed multiple enlarged cystic follicles with diminished corpora lutea in PCOS ovaries, whereas LUP administration substantially improved folliculogenesis and luteal development. Immunohistochemical analysis further demonstrated elevated caspase-3 expression in granulosa cells of PCOS ovaries, which was significantly suppressed by LUP in a dose-dependent manner. Collectively, these findings indicate that lupeol exerts potent antioxidant, anti-apoptotic, and hormone-modulatory effects, highlighting its promise as a novel phytotherapeutic candidate for the management of polycystic ovary syndrome.