Therapeutic Effect of Ecklonia cava Extract in Letrozole-Induced Polycystic Ovary Syndrome Rats

Yang, Hyun; Lee, Seung Yeon; Lee, Sang R; Pyun, Bo-Jeong; Kim, Hye Jin; Lee, Young Ho; Kwon, Sun Woo; Suh, Dong Ho; Lee, Choong Hwan; Hong, Eui-Ju; Lee, Hye Won

doi:10.3389/fphar.2018.01325

Cited by 43 publications

(37 citation statements)

References 38 publications

(47 reference statements)

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“…The reported elevation in testosterone and LH hormones in LTZ induced PCOS rat models (9,67,68) were signi cantly restored by AR (Figure 2A and B). Similar data were reported on isolated cells from ovariectomized rats (22,69) and on the ovariectomized rats (70).…”

Section: Discussionmentioning

confidence: 81%

“…Various side effects are associated with chemical and hormonal PCOS therapies such as hyperplasia, uterine bleeding and uncertain risks (9,10) along with considerable cost (11), nonetheless, these therapies may not be effective in some cases. Therefore, several studies are focused on the investigation of complementary herbal medicine as a potential treatment of PCOS (9,(12)(13)(14)(15)(16). For instance, promising effects of hops (Humulus lupulus), female ginseng (Angelica sinensis), ginseng (Panax ginseng), liquorice (Glycyrrhiza glabra), black cohosh (Actaea racemosa) and kelp (Nereocystis leutkeana) were reported against PCOS (17).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: Promising activity without the risk of hepatic adverse effect

Azouz

Ali

Abd‐Elsalam

et al. 2020

Preprint

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Background: Complementary remedies such as the Chinese herb ‘Sheng Ma’ (Black cohosh; Actaea racemosa ‘AR’) are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for treatment of polycystic ovary syndrome (PCOS). However, the AR hepatotoxicity urges a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products.Methods: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed then rats received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, a holistic profiling of AR arsenal of secondary metabolites was performed using ultra high-performance liquid chromatography (UHPLC) coupled with quadrupole high resolution time of flight mass spectrometry (QTOF-MS).Results: Beneficial effects were exerted by AR in PCOS rats via the improved antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic MDA and GSH levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes.Conclusion: This study demonstrated the benefit of the combination between AR and vitamin C in mitigating the reproductive and metabolic disorders of PCOS with the elimination of AR hepatotoxic risk.

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: Promising activity without the risk of hepatic adverse effect

Azouz

Ali

Abd‐Elsalam

et al. 2020

Preprint

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“…A new therapeutic approach with fewer side effects, easy availability, and broad spectrum is required. Previous studies reported the efficacy of some plants such as Trigonella foenum-graecum [2], Ecklonia cava [14] and Allium fistulosum [12] in the restoration of ovarian function in PCOS rats. Phyllanthus muellerianus (Kuntze) Exell (Euphorbiaceae) commonly called “Mbolongo” in eastern Cameroon, is a tropical plant extensively used for the treatment of digestive disorders, frequent menstruation and anovulation [15, 16].…”

Section: Introductionmentioning

confidence: 99%

Phyllanthus muellerianus(Euphorbiaceae) Restores Ovarian Functions in Letrozole-Induced Polycystic Ovarian Syndrome in Rats

Ndeingang

Deeh

Watcho

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Polycystic ovarian syndrome (PCOS) is one of the common causes or female infertility. Phyllanthus muellerianus (Euphorbiaceae) is a plant used to treat various ailments including frequent menstruation and anovulation. We investigated the effects of P. muellerianus extracts on estrus cyclicity, lipid profile, oxidative stress-related markers, sex hormones, and ovarian architecture in letrozole-induced PCOS in rats. After induction of PCOS using letrozole (1 mg/kg/day), normal (n=6), and PCOS (n=108; distributed into 18 groups of 6 animals/group) rats were treated orally for 7 or 14 days with distilled water (10 ml/kg/day), clomiphene citrate (2 mg/kg/day), metformin (500 mg/kg/day), and aqueous or methanolic extract of P. muellerianus (30, 60, and 120 mg/kg). Estrus cyclicity, body, and sexual organ (ovaries and uterus) weights, biochemical and histological parameters were measured. There were letrozole-induced PCOS characterized by irregular estrus cyclicity, elevated (p<0.05-0.01) glycaemia, ovarian weight, triglycerides, total cholesterol, LDL cholesterol, VLDL cholesterol, malondialdehyde, luteinizing hormone (LH), and testosterone concentrations, but there were low (p<0.05-0.001) HDL cholesterol, estradiol, progesterone, catalase, peroxidase, and superoxide dismutase levels, compared with control. PCOS rats had multiple cysts compared with control. These reproductive, biochemical, and structural alterations were alleviated by P. muellerianus extracts. For instance, P. muellerianus restored the estrus cyclicity with a remarkable effect after 14 days of treatment. Moreover, P. muellerianus significantly decreased (p<0.001) LH and testosterone (both extracts; 30, 60, and 120 mg/kg) levels, but increased (p<0.01) estradiol (aqueous extract; 60 mg/kg) concentration. Cystic follicles were also decreased after plant application. P. muellerianus alleviated reproductive, hormonal, and structural alterations in PCOS rats. This plant could be useful in the management/treatment of reproductive and metabolic disorders related to PCOS.

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“…The reported elevation in testosterone and LH hormones in LTZ induced PCOS rat models (8,56,57) were significantly restored by AR (Figure 2A and B). Similar data were reported on the treated cells isolated from ovariectomized rats (14,58) and on the ovariectomized rats (59).…”

Section: Discussionmentioning

confidence: 80%

“…Various side effects are associated with chemical and hormonal PCOS therapies such as hyperplasia, uterine bleeding and uncertain risks (8,9) along with considerable cost (10), nonetheless, these therapies may not be effective in some cases. Therefore, several studies are focused on the investigation of complementary herbal medicine as a possible treatment of PCOS (8,11). For instance, promising effects of hops, dong qui, ginseng , liquorice, black cohosh and kelp against PCOS were reported (12).…”

Section: Introductionmentioning

confidence: 99%

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in Letrozole induced polycystic ovarian syndrome rat model: Promising activity without the risk of hepatic adverse effect

Azouz

Ali

Abd‐Elsalam

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Complementary remedies such as the Chinese herb ‘Sheng Ma’ (Black cohosh; Actaea racemose ‘AR’) are being sought to surmount the shortcomings of conventional hormonal and surgical therapies developed in the treatment of polycystic ovary syndrome (PCOS). However, the AR hepatotoxicity urges a cautionary warning to be labelled on its products as recommended by the United States Pharmacopeia where 4 out of 7 hepatotoxic cases in Sweden were possibly associated with black cohosh products.Methods We investigated the efficacy, safety and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality, oxidative response in the hyperandrogenism-induced PCOS alongside with holistic profiling of its arsenal of secondary metabolites using UPLC-Qtof-MS. A well-established rat model using oral letrozole, daily, for 21 days was employed then the rats received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, apoptosis, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated.Results Beneficial effects were exerted by AR in PCOS rats via the improved antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, curtailed percentage of apoptotic cells and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells. Notably, AR combination with vitamin C was not only more effective to reverse the dysregulated levels of testosterone, luteinising hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer, while the combination regulated both ovarian and hepatic MDA and GSH levels with a histologic improvement noticed in livers and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes.Conclusion This study demonstrated the benefit of the combination between AR and vitamin C in mitigating the reproductive and metabolic disorders of PCOS with the elimination of AR hepatotoxic risk.

show abstract

Therapeutic Effect of Ecklonia cava Extract in Letrozole-Induced Polycystic Ovary Syndrome Rats

Cited by 43 publications

References 38 publications

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: Promising activity without the risk of hepatic adverse effect

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: Promising activity without the risk of hepatic adverse effect

Phyllanthus muellerianus(Euphorbiaceae) Restores Ovarian Functions in Letrozole-Induced Polycystic Ovarian Syndrome in Rats

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in Letrozole induced polycystic ovarian syndrome rat model: Promising activity without the risk of hepatic adverse effect

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