Diacerein ameliorates letrozole-induced polycystic ovarian syndrome in rats

Ibrahim, Yasmine; Alorabi, Mohammed; Abdelzaher, Walaa Yehia; Toni, Nisreen D. M.; Thabet, Khaled; Hegazy, AbdelRahman; Bahaa, Haitham Ahmed; Batiha, Gaber El‐Saber; Welson, Nermeen N.; Morsy, Mohamed A.; Venugopala, Katharigatta N.; Abdel-Aziz, Asmaa Mohamed

doi:10.1016/j.biopha.2022.112870

Cited by 40 publications

(33 citation statements)

References 84 publications

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“…A similar trend was recorded in the clomiphene and metformin groups or in the combination of KH with both drugs. In agreement with previous studies [ 62 , 70 , 71 ], metformin and clomiphene were reported to reverse the elevated testosterone level in letrozole-induced PCOS rats. In women with PCOS, metformin causes a rapid decrease in LH-stimulated testosterone secretion [ 72 ].…”

Section: Discussionsupporting

confidence: 93%

“…Similarly, Ndeingang et al also found that clomiphene treatment does not affect the LH levels in PCOS rats [ 34 ]. Meanwhile, Ibrahim et al discovered that metformin treatment reduced LH increment in PCOS-induced rats [ 71 ]. In a previous study, six months of metformin treatment successfully reduced the LH levels in women with PCOS [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

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Kelulut Honey Ameliorates Oestrus Cycle, Hormonal Profiles, and Oxidative Stress in Letrozole-Induced Polycystic Ovary Syndrome Rats

et al. 2022

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Kelulut honey (KH) has been proven to have excellent antioxidative and anti-inflammatory properties with unique physicochemical characteristics. Therefore, we investigated the isolated and combined effects of KH, metformin, or clomiphene in alleviating oxidative stress and reproductive and metabolic abnormalities in polycystic ovary syndrome (PCOS). Female Sprague-Dawley (SD) rats were given 1 mg/kg/day of letrozole for 21 days to induce PCOS. PCOS rats were then divided into six treatment groups: untreated, metformin (500 mg/kg/day), clomiphene (2 mg/kg/day), KH (1 g/kg/day), combined KH (1 g/kg/day) and metformin (500 mg/kg/day), and combined KH (1 g/kg/day) and clomiphene (2 mg/kg/day). All treatments were administered orally for 35 days. The physicochemical characteristics of KH were assessed through hydroxymethylfurfural, free acidity, diastase number, moisture content, sugar profile, metals, and mineral compounds. Additionally, we determined the semivolatile organic compounds present in KH through gas chromatography-mass spectrometry (GC/MS) analysis. KH and its combination with metformin or clomiphene were shown to improve the oestrus cycle, hormonal profile, and oxidative stress in PCOS rats. However, KH did not reduce the fasting blood glucose, insulin, and body weight gain in PCOS rats. These findings may provide a basis for future studies to discover the potential use of KH as a complementary treatment for women with PCOS.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Kelulut Honey Ameliorates Oestrus Cycle, Hormonal Profiles, and Oxidative Stress in Letrozole-Induced Polycystic Ovary Syndrome Rats

et al. 2022

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“…Letrozole, an aromatase inhibitor, effectively induces PCOS in rats [ 33 , 34 ]. It resulted in excess androgens accumulating in the ovary, affecting the follicle development and leading to anovulation and insulin resistance which are the hallmark of PCOS [ 35 , 36 ]. Letrozole-induced PCOS rats also developed hyperandrogenism, ovarian cyst formation, abnormal follicles, hyperglycaemia, and oxidative stress similar to human PCOS [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Kelulut Honey on Oestrus Cycle Regulation and Histomorphological Changes in Letrozole-Induced Polycystic Ovary Syndrome Rats: A Preliminary Study

Kamal

Ibrahim

Ugusman

et al. 2022

Life

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Polycystic ovary syndrome (PCOS) is a complex reproductive, metabolic, and endocrine disorder that affects women of reproductive age. Kelulut honey is stingless bee honey that possesses anti-inflammatory, anti-cancer, anti-diabetic, and potent antioxidative activities in most conditions. However, its value in improving PCOS remains to be elucidated. Thus, this preliminary study aimed to determine the effective dose of Kelulut honey in oestrus cycle regulation and ovarian histomorphological changes in letrozole-induced PCOS rats. PCOS was induced in all-female Sprague Dawley (SD) rats with 1 mg/kg/day of letrozole except for the control group for 21 days. Kelulut honey was then orally administered to the PCOS rats at the dose of 0.5, 1, or 2 g/kg/day, respectively, for 35 days. The oestrous cycle was determined through vaginal smears, while ovarian histomorphological changes were observed by haematoxylin and eosin (H&E) staining. The untreated PCOS rats were characterised by irregular oestrous cyclicity, hyperglycaemia, and aberrant ovarian histology. In this study, Kelulut honey (1 g/kg/day) increased the number of corpus luteum and antral follicles (p < 0.05), improved the cystic follicle, and normalised the oestrus cycle (p < 0.05). This preliminary study demonstrated that Kelulut honey, particularly at a dose of 1 g/kg/day, has the potential to alleviate oestrus cycle dysregulation and ovarian histomorphological changes occurring in PCOS.

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“…Metformin, the most widely used insulin sensitizer for PCOS, reduces hepatic glucose production, inhibits gluconeogenesis and adipogenesis, improves peripheral tissue sensitivity to insulin, and prevents excessive insulin activity in the ovary [153]. Numerous studies have shown that metformin not only reduces weight and metabolic disorders but also corrects menstrual patterns, restores ovulation, and even improves chances of pregnancy [154].…”

Section: Insulin Sensitization Therapy Metforminmentioning

confidence: 99%

Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment

et al. 2023

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Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic ovulation dysfunction and overabundance of androgens; it affects 6–20% of women of reproductive age. PCOS involves various pathophysiological factors, and affected women usually have significant insulin resistance (IR), which is a major cause of PCOS. IR and compensatory hyperinsulinaemia have differing pathogeneses in various tissues, and IR varies among different PCOS phenotypes. Genetic and epigenetic changes, hyperandrogenaemia, and obesity aggravate IR. Insulin sensitization drugs are a new treatment modality for PCOS. We searched PubMed, Google Scholar, Elsevier, and UpToDate databases in this review, and focused on the pathogenesis of IR in women with PCOS and the pathophysiology of IR in various tissues. In addition, the review provides a comprehensive overview of the current progress in the efficacy of insulin sensitization therapy in the management of PCOS, providing the latest evidence for the clinical treatment of women with PCOS and IR.

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Diacerein ameliorates letrozole-induced polycystic ovarian syndrome in rats

Cited by 40 publications

References 84 publications

Kelulut Honey Ameliorates Oestrus Cycle, Hormonal Profiles, and Oxidative Stress in Letrozole-Induced Polycystic Ovary Syndrome Rats

Kelulut Honey Ameliorates Oestrus Cycle, Hormonal Profiles, and Oxidative Stress in Letrozole-Induced Polycystic Ovary Syndrome Rats

Effects of Kelulut Honey on Oestrus Cycle Regulation and Histomorphological Changes in Letrozole-Induced Polycystic Ovary Syndrome Rats: A Preliminary Study

Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment

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