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Myo-inositol supplementation has displayed effectiveness in curing PCOS patients. Diacerein, an anti-inflammatory medication, has not been extensively studied in the context of reproductive disorders. This study aimed to compare the role of myo-inositol and diacerein in PCOS and the probable mechanisms mediating their actions. Forty adult female rats were divided equally into the following: control, PCOS, PCOS+Myo-inositol, and PCOS+Diacerein groups. Rats were subjected to arterial blood pressure (ABP), electromyography (EMG), and uterine reactivity measurements. Blood samples were collected for measuring hormonal assays, glycemic state, lipid profile, oxidative stress, and inflammatory markers. Ovaries and uteri were extracted for histological examination, including hematoxylin and eosin staining, Masson\u2019s trichrome staining, immunohistochemistry, and rt-PCR analysis of ovarian tissues. PCOS was associated with significant increases in ABP, uterine frequency and amplitude of contraction, luteinizing hormone, testosterone, lipid, glycemic and inflammatory markers, malondialdehyde, high-mobility group box 1 (HMGB1), nuclear factor kappa (NF-kB), ovarian fibrosis, and endometrial thickening. In contrast, there was a significant reduction in follicular stimulating hormone, reduced glutathione, and Sirtuin 1 (SIRT1) when compared with control group. Both myo-inositol and diacerein counteract PCOS changes; but diacerein\u2019s effects\u00a0were superior\u00a0to myo-inositol\u2019s for all parameters, except for lipid and glycemic markers. Diacerein possessed anti-inflammatory properties and showed significant efficacy in mitigating the endocrinal, metabolic, and ovarian structural alterations linked to PCOS. Its beneficial actions likely stem from reducing oxidative stress, dyslipidemia, and hyperglycemia, potentially through the modulation of HMGB1, SIRT1, and NF-kB pathways.<\/jats:p>","DOI":"10.1007\/s00210-024-03497-7","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T08:02:51Z","timestamp":1729497771000},"page":"4179-4197","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Diacerein and myo-inositol alleviate letrozole-induced PCOS via modulation of HMGB1, SIRT1, and NF-kB: A comparative study"],"prefix":"10.1007","volume":"398","author":[{"given":"Suzan A.","family":"Khodir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Sweed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa Mohamed","family":"Motawea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa A.","family":"Al-Gholam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherin Sobhy","family":"Elnaidany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Zakaria Sayer","family":"Dayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia","family":"Ameen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"3497_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.lfs.2018.07.060","volume":"209","author":"SA Abdel-Gaber","year":"2018","unstructured":"Abdel-Gaber SA, Mohammed RK, Refaie MMM (2018) Mechanism mediating the protective effect of diacerein in ischemia-reperfusion-induced testicular injury in rats. 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