scholarly journals Mangiferin ameliorates insulin resistance in a rat model of polycystic ovary syndrome via inhibition of inflammation

2020 ◽  
Vol 19 (1) ◽  
pp. 89-94
Author(s):  
Qiaohong Qian ◽  
Minjie Tang ◽  
Xinrong Li ◽  
Qi Cao ◽  
Zhiling Zhu

Purpose: To examine the effect of mangiferin on insulin resistance (IR) in a rat polycystic ovary syndrome (PCOS) model.Methods: The rat PCOS model was established via subcutaneous injection of 6 mg/kg of dehydroepiandrosterone (DHEA), and mangiferin was orally administered. Body and ovarian weights were recorded. Serum levels of glucose, insulin, and related inflammatory cytokines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay, while the expression levels of key proteins were analyzed by western blotting.Results: DHEA significantly increased ovarian weight and the ratio of ovarian weight/body weight (p <0.001), while mangiferin treatment decreased them (p < 0.001). Mangiferin also lowered DHEA-induced enhancements in serum glucose and insulin levels (p < 0.001). The mRNA and, expression and concentrations of inflammatory cytokines (interleukin-6(IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) were also significantly reduced by mangiferin treatment (p < 0.001). Furthermore, mangiferin suppressed phosphorylation of nuclear factor-kappa B (NF-κB) but increased the phosphorylation of protein kinase B (AKT, p < 0.001).Conclusion: These results reveal that mangiferin not only decreases inflammatory cytokine levels by regulating NF-κB signaling pathway but also ameliorates IR in a rat PCOS model via regulating AKT signaling pathway. Thus, mangiferin is a potential therapeutic strategy for the management of PCOS. Keywords: Polycystic ovary syndrome, Mangiferin, Inflammation, Insulin resistance, NF-κB, AKT

2019 ◽  
Vol 8 (6) ◽  
pp. 709-717
Author(s):  
Shilpa Lingaiah ◽  
Laure Morin-Papunen ◽  
Terhi Piltonen ◽  
Inger Sundström-Poromaa ◽  
Elisabet Stener-Victorin ◽  
...  

Objective Serum levels of retinol-binding protein 4 (RBP4), an adipokine thought to affect systemic insulin sensitivity, were compared between women with polycystic ovary syndrome (PCOS) and non-PCOS controls to evaluate the association of RBP4 with clinical, hormonal and metabolic parameters of PCOS. Subjects and methods Serum RBP4 levels were analysed in 278 women with PCOS (age range 18–57 years) and 191 non-PCOS controls (age 20–53 years) by enzyme-linked immunosorbent assay. Results Serum levels of RBP4 were increased in women with PCOS compared with control women in the whole population (45.1 ± 24.0 (s.d.) vs 33.5 ± 18.3 mg/L, P < 0.001). Age-stratified analysis showed that serum RBP4 levels were increased in women with PCOS aged ≤30 years compared with controls (47.7 ± 23.5 vs 27.1 ± 10.4 mg/L, P < 0.001), whereas no significant differences were seen in the other age groups. No significant correlations of RBP4 were seen with either steroids or indices of insulin resistance. Conclusions Although serum RBP4 levels were increased in younger women with PCOS compared with age-matched non-PCOS controls, RBP4 does not seem to be a good marker of insulin resistance or other metabolic derangements in women with PCOS.


2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Yun-yun Shao ◽  
Zhuang-peng Chang ◽  
Yao Cheng ◽  
Xin-chun Wang ◽  
Jing-ping Zhang ◽  
...  

Abstract Shaoyao-Gancao Decoction (SGD) has been widely used for the treatment of gynopathy. The present study aimed to evaluate the therapeutic effect and potential mechanism of SGD on hyperandrogenism in polycystic ovary syndrome (PCOS) rats. In the present work, SGD was orally administrated to the PCOS rats at the dose of 12.5, 25, and 50 g/kg/d for 14 consecutive days. UPLC–MS/MS was performed to identify the main chemical components of SGD. Body weight, ovarian weight, cystic dilating follicles, and serum levels of steroid hormones were tested to evaluate the therapeutic effect of SGD. In order to further clarify the underlying mechanism, we also measured mRNA and the protein levels of NF-κB, NF-κB p65, P-NF-κB p65, and IκB by RT-qPCR and Western blotting techniques. Our results showed that SGD treatment significantly alleviated hyperandrogenism in PCOS rats as evidenced by reduced serum levels of T and increased E2 and FSH levels. In addition, SGD effectively reduced the phosphorylation of NF-κB p65 and increased the expression of IκB. Results of the present study demonstrated that SGD could ameliorate hyperandrogenism in PCOS rats, and the potential mechanism may relate to the NF-κB pathway.


Author(s):  
Shouzhen Chen ◽  
Mei Jiang ◽  
Tao Ding ◽  
Junmei Wang ◽  
Ping Long

Background Calprotectin is an antimicrobial, calcium and zinc-binding heterocomplex protein and has been proposed as a marker to rule out inflammatory conditions. The aim of this study was to evaluate the role of calprotectin in the diagnosis of polycystic ovary syndrome and to investigate the association between calprotectin and insulin resistance. Methods A total of 41 females with polycystic ovary syndrome and 54 age-matched without polycystic ovary syndrome were eligible for the study. Serum concentration of calprotectin was determined using enzyme-linked immunosorbent assay. Clinical characteristics, hormone and metabolic parameters were evaluated in each subject. The predictive value of serum calprotectin was assessed using receiver operating characteristic curves. Correlations between the serum calprotectin concentrations and insulin resistance were examined using Spearman’s correlation. Results We found that the serum calprotectin concentrations were significantly higher in polycystic ovary syndrome compared with the non-polycystic ovary syndrome group ( P < 0.001). The area under the receiver operating characteristic curve assay yielded a satisfactory result of 0.88 (95% confidence interval 0.81–0.95; P < 0.001). The optimum cut-off was 2.4  µg/mL with a 85.2% specificity and 75.6% sensitivity for polycystic ovary syndrome diagnosis. A significant positive correlation was found between the serum calprotectin and insulin resistance. Conclusions These results suggest that calprotectin might be a useful adjunct in the diagnosis of polycystic ovary syndrome, especially those with insulin resistance.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuang-peng Chang ◽  
Gui-feng Deng ◽  
Yun-yun Shao ◽  
Ding Xu ◽  
Yi-nan Zhao ◽  
...  

Background: Emerging evidence suggests that gut microbiota plays a vital role in the occurrence of multiple endocrine disorders including polycystic ovary syndrome (PCOS). Shaoyao-Gancao Decoction (SGD), a classical Chinese prescription, has been widely used in the treatment of PCOS for decades. In previous studies, we found that SGD treatment could effectively reduce ovarian inflammation in PCOS rats. However, whether the anti-inflammation effect of SGD involves the regulation of the gut microbiota remains elusive.Methods: Letrozole-induced PCOS rat models were established, and the therapeutic effects of SGD were evaluated. Specifically, body weight, serum hormone concentrations, estrus phase and ovary histopathology were assessed. Then the structure of gut microbiota was determined by 16s rRNA sequencing. Additionally, the serum levels of pro-inflammatory cytokines and LPS were measured by ELISA kits. The key gene and protein expressions of TLR4/NF-κB signaling pathway were detected by quantitative real-time PCR and western blot.Results: SGD could effectively reduce body weight, regulate estrous cycles and ameliorate hyperandrogenism in PCOS rats. In addition, SGD treatment decreased releases of pro-inflammatory cytokines, enhanced the expressions of tight junction (occludin and claudin1), and then prevented a translocation of LPS into bloodstream. SGD could significantly reduce the ratio of Firmicutes to Bacteroidetes, decrease the abundance of LPS-producing pathogens Proteobateria and enrich the abundance of Butyricicoccus, Coprococcus, Akkermansia Blautia and Bacteroides in PCOS rats. Furthermore, SGD blunted the key gene and protein expressions of TLR4/NF-κB signaling pathway both in vivo and in LPS-induced RAW264.7 cells.Conclusion: SGD administration could ameliorate the inflammatory response in PCOS rats by remodeling gut microbiome structure, protecting gut barrier, and suppressing TLR4/NF-κB signaling pathway.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Nearmeen M. Rashad ◽  
Amal S. El-Shal ◽  
Hala G. Abomandour ◽  
Amr Mostafa Kamel Aboelfath ◽  
Mohamed el sayed Rafeek ◽  
...  

Abstract Background Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. Intercellular adhesion molecule-1 (ICAM-1) is a proinflammatory and proatherogenic cytokine which is associated with atherosclerosis, insulin resistance, and cardiovascular disease (CVD). The pathogenesis of PCOS is not precisely known. Thus, the purpose of this study was to investigate the potential role of ICAM-1 expression and serum ICAM-1 concentrations in pathogenesis of PCOS. Moreover, we aimed to evaluate the possible relationship between ICAM-1 gene expression with carotid intima-media thickness as well as clinic-morphological features of PCOS. Methods This case control study enrolled 180 patients with PCOS and 120 controls groups and they were stratified according to their fasting plasma glucose (FPG) into three subgroups; normal glucose tolerance (NGT) [n = 75], those with impaired glucose tolerance (IGT) [n = 65], and 40 patients with type 2 diabetes mellitus (T2DM). Circulating ICAM-1 expression levels were determined by real time polymerase chain reaction (RT-PCR). Serum ICAM-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Results Our results revealed that PCOS patients had higher values of ICAM-1expression and serum levels. Among PCOS patients, T2DM patients had the highest values of ICAM-1 expression and serum levels compared to IGT and NGT subgroups. The ICAM-1 expression and serum levels were significantly positive correlated with cardiovascular risk and PCOS phenotypes. Linear regression test showed that HOMA-IR was the main predictors of serum ICAM-1 levels in PCOS. Receiver operating characteristic curve (ROC) analysis revealed that, the power of ICAM-1 expression levels was higher than serum ICAM-1 in diagnosis of PCOS and in differentiating T2DM from IGT and NGT subgroups. Interestingly, combination of both ICAM-1 expression and serum levels improved the diagnostic role of serum ICAM-1. Conclusion ICAM-1 expression and serum levels were higher in women with PCOS compared to control group also, there was a strong independent association between higher ICAM-1 expression and serum levels with cardiovascular risks in PCOS group.


2018 ◽  
Vol 103 (7) ◽  
pp. 2457-2467 ◽  
Author(s):  
Jia Qi ◽  
Wangsheng Wang ◽  
Qinling Zhu ◽  
Yaqiong He ◽  
Yao Lu ◽  
...  

Abstract Context Endometrial insulin resistance (IR) may account for the endometrial dysfunction in polycystic ovary syndrome (PCOS). The underlying mechanism remains to be elucidated. Objective To investigate whether the abundance of 11β-hydroxysteroid dehydrogenases (11β-HSDs) 1 and 2 and cortisol as well as the insulin signaling pathway are altered in PCOS endometrium and to clarify the relationship between endometrial IR and local cortisol. Design We measured cortisol and cortisone concentrations, 11β-HSD1 and 11β-HSD2, and core insulin signaling molecules in endometrial biopsies collected from non-PCOS and PCOS with or without IR patients on the seventh day after human chorionic gonadotropin injection. We also studied the effects of cortisol on glucose uptake and the insulin signaling pathway in primary cultured endometrial epithelial cells (EECs). Results The cortisol concentration was elevated, whereas 11β-HSD2 expression was diminished in endometrial biopsies obtained from PCOS with IR patients compared with those from non-PCOS and PCOS without IR patients. The implantation rate was relatively impaired and the endometrial insulin signaling pathway was defective in PCOS with IR patients. In addition, cortisol attenuated insulin-stimulated glucose uptake in EECs, which was mediated by inhibition of Akt phosphorylation and glucose transporter type 4 translocation via induction of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Conclusions Decreased oxidation of cortisol and defects of insulin signaling in endometrium were observed in PCOS with IR patients. The excessive cortisol level, derived from the reduction of 11β-HSD2, might contribute to the development of endometrial IR by inhibiting the insulin signaling pathway via induction of PTEN expression in EECs.


Endocrine ◽  
2006 ◽  
Vol 29 (3) ◽  
pp. 419-424 ◽  
Author(s):  
Yi-fei Zhang ◽  
Yi-sheng Yang ◽  
Jie Hong ◽  
Wei-qiong Gu ◽  
Chun-fang Shen ◽  
...  

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