scholarly journals Evaluation of the inhibitory potentials of selected compounds from Costus spicatus (Jacq.) rhizome towards enzymes associated with insulin resistance in polycystic ovarian syndrome: an in silico study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fehintoluwa Joy Femi-Olabisi ◽  
Ahmed Adebayo Ishola ◽  
Opeyemi Faokunla ◽  
Anthonia Oluyemi Agboola ◽  
Benjamin Ayodipupo Babalola
Keyword(s):  
Insulin Resistance ◽  
Aqueous Extract ◽  
In Silico ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Polycystic Ovary ◽  
Premenopausal Women ◽  
Amino Acid Residues ◽  
Binding Modes ◽  
Discovery Studio ◽  
Reproductive Endocrine

Abstract Background Polycystic ovary syndrome (PCOS) is a chronic endocrine disorder prevalent in premenopausal women and is characterized by a range of physiological and biochemical abnormalities which may include reproductive, endocrine, and metabolic alterations such as insulin resistance. Insulin resistance is the hallmark of PCOS as it predisposes the affected subjects to a higher risk of impaired glucose tolerance and type 2 diabetes mellitus (T2DM). In this study, the inhibitory activities of phytosterols and saccharides from aqueous extract of Costus spicatus rhizome were investigated against phosphoenolpyruvate carboxykinase (PEPCK), α-amylase, β-glucosidase, and fructose 1,6-biphosphatase (FBPase) in silico as potential novel therapeutic targets for T2DM-associated-PCOS. Phytochemical constituents of the plant were determined using gas chromatography-mass spectrophotometry (GC-MS), while molecular docking of the compounds with PEPCK, α-amylase, β-glucosidase, and FBPase was conducted using Vina. Thereafter, the binding modes were determined using Discovery Studio Visualizer, 2020. Results GCMS analysis of an aqueous extract of Costus spicatus rhizome revealed the presence of three compounds with a higher binding affinity for all enzymes studied compared to metformin. The compounds also interacted with key amino acid residues crucial to the enzyme’s activities. This study identified Lyxo-d-manno-nononic-1,4-lactone as potential multi-target inhibitors of PEPCK, α-amylase, β-glucosidase, and FBPase with reasonable pharmacokinetic properties and no significant toxicity. Conclusion These compounds can be explored as potential therapeutic agents for the management of insulin resistance in PCOS, subject to further experimental validation.

scholarly journals Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Tommy Kyaw Tun ◽  
Anne McGowan ◽  
Niamh Phelan ◽  
Neuman Correia ◽  
Gerard Boran ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Risk ◽  
Polycystic Ovary Syndrome ◽  
Apolipoprotein B ◽  
Polycystic Ovary ◽  
Density Lipoprotein ◽  
Premenopausal Women ◽  
Postprandial Glucose ◽  
Ovary Syndrome ◽  
Mixed Meal

Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age30.4±1.2years (mean ± SEM), body mass index (BMI)36.8±1.5 kg/m2) and 26 non-PCOS subjects (age34.1±0.9years, BMI31.5±1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden.

scholarly journals Effects of Metformin on Reproductive, Endocrine, and Metabolic Characteristics of Female Offspring in a Rat Model of Letrozole-Induced Polycystic Ovarian Syndrome With Insulin Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Yidong Xie ◽  
Li Xiao ◽  
Shangwei Li
Keyword(s):  
Insulin Resistance ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Body Weight Gain ◽  
Female Offspring ◽  
Female Rats ◽  
Metabolic Characteristics ◽  
Continuous Release ◽  
Reproductive Endocrine ◽  
The Impact

The beneficial effects of metformin, especially its capacity to ameliorate insulin resistance (IR) in polycystic ovary syndrome (PCOS), explains why it is widely prescribed. However, its effect on the offspring of patients with PCOS remains uncertain. This study investigated the impact of metformin treatment on the first- and second-generation female offspring born to letrozole-induced PCOS-IR rats. Forty-five female Wistar rats were implanted with continuous-release letrozole pellets or placebo and treated with metformin or vehicle control. Rats exposed to letrozole showed PCOS-like reproductive, endocrine, and metabolic phenotypes in contrast to the controls. Metformin significantly decreased the risk of body weight gain and increased INSR expression in F1 female offspring in PCOS-IR rats, contributing to the improvement in obesity, hyperinsulinemia, and IR. Decreased FSHR expression and increased LHCGR expression were observed in F1 female rats of the PCOS-IR and PCOS-IR+Metformin groups, suggesting that FSHR and LHCGR dysfunction might promote the development of PCOS. Nevertheless, we found no significant differences in INSR, FSHR, and LHCGR expression or other PCOS phenotypes in F2 female offspring of PCOS-IR rats. These findings indicated widespread reproductive, endocrine, and metabolic changes in the PCOS-IR rat model, but the PCOS phenotypes could not be stably inherited by the next generations. Metformin might have contributed to the improvement in obesity, hyperinsulinemia, and IR in F1 female offspring. The results of this study could be used as a theoretical basis in support of using metformin in the treatment of PCOS-IR patients.

scholarly journals Risk of Insulin Resistance and Metabolic Syndrome in Women with Hyperandrogenemia: A Comparison between PCOS Phenotypes and Beyond

2021 ◽  
Vol 10 (4) ◽  
pp. 829
Author(s):  
Valentin Borzan ◽  
Elisabeth Lerchbaum ◽  
Cornelia Missbrenner ◽  
Annemieke C. Heijboer ◽  
Michaela Goschnik ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Diseases ◽  
Polycystic Ovary ◽  
Wide Spectrum ◽  
Premenopausal Women ◽  
Healthy Controls ◽  
Therapeutic Approaches ◽  
Ovary Syndrome ◽  
Rotterdam Criteria

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in premenopausal women, with a wide spectrum of possible phenotypes, symptoms and sequelae according to the current clinical definition. However, there are women who do not fulfill at least two out of the three commonly used “Rotterdam criteria” and their risk of developing type 2 diabetes or obesity later in life is not defined. Therefore, we addressed this important gap by conducting a retrospective analysis based on 750 women with and without PCOS. We compared four different PCOS phenotypes according to the Rotterdam criteria with women who exhibit only one Rotterdam criterion and with healthy controls. Hormone and metabolic differences were assessed by analysis of variance (ANOVA) as well as logistic regression analysis. We found that hyperandrogenic women have per se a higher risk of developing insulin resistance compared to phenotypes without hyperandrogenism and healthy controls. In addition, hyperandrogenemia is associated with developing insulin resistance also in women with no other Rotterdam criterion. Our study encourages further diagnostic and therapeutic approaches for PCOS phenotypes in order to account for varying risks of developing metabolic diseases. Finally, women with hyperandrogenism as the only symptom should also be screened for insulin resistance to avoid later metabolic risks.

scholarly journals Effects of Metformin on Reproductive, Endocrine, and Metabolic Characteristics of Female Offspring in a Rat Model of Letrozole-induced Polycystic Ovarian Syndrome With Insulin Resistant

2020 ◽  
Author(s):  
Yidong Xie ◽  
Li Xiao ◽  
Xiaohan Shi ◽  
Yifan Zhao ◽  
Xiaohong Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Wistar Rats ◽  
Polycystic Ovary ◽  
Female Offspring ◽  
Ovary Syndrome ◽  
Metabolic Characteristics ◽  
Reproductive Endocrine ◽  
The Impact

Abstract Background: Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder that has many characteristic features including hyperandrogenemia, insulin resistance and obesity. The beneficial effects of metformin on reproduction, metabolism and endocrine, especially with the capacity to ameliorate insulin resistance (IR) in polycystic ovary syndrome (PCOS), place it as a good alternative for its widely prescribed, but its association with PCOS offspring remains uncertain. We aim to investigate the impact of metformin on reproductive, endocrine and metabolic characteristics in female offspring born to letrozole-induced PCOS-IR rats.Methods: 45 female wistar rats were implanted with letrozole-continuous-release pellets or placebo, subsequently treated with metformin or vehicle control, then mated with healthy male wistar rats. Estrous cycle, endocrine hormone profile, fasting insulin measurements and glucose tolerance test have been investigated and the expression of INSR in pancreas, FSHR and LHCGR in ovaries have been analyzed with Quantitative Real-time Polymerase Chain Reaction and Western Blotting assay.Results: Decreased conception rate and increased multiple pregnancy rates were found in PCOS-IR rats, which significantly improved after metformin treatment. Metformin significantly decreased the risk of body weight gain and increased INSR expression of pancreas in female F1 offspring in PCOS-IR rats. Decreased FSHR and increased LHCGR expressions in ovary were observed in female F1 rats of PCOS-IR and PCOS-IR+Met group. Nevertheless, there were no significant differences of INSR, FSHR and LHCGR expressions in female F2 offspring of PCOS-IR rats, as well as other PCOS phenotypes.Conclusions: The current study indicates that widespread reproductive, endocrine and metabolic changes in letrozole induced PCOS-IR rat model, but those PCOS phenotypes could not be inherit to offspring generations stably. Metformin may contribute to improve obesity, hyperinsulinemia and insulin resistance of female F1 offspring in PCOS-IR. The results of this study can be used as a theoretical basis for supporting metformin-using in the treatment of PCOS-IR patients.

scholarly journals Assessing C reactive protein/albumin ratio as a new biomarker for polycystic ovary syndrome: a case–control study of women from Bahraini medical clinics

BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e021860 ◽  
Author(s):  
Shirin Kalyan ◽  
Azita Goshtesabi ◽  
Sameh Sarray ◽  
Angela Joannou ◽  
Wassim Y Almawi
Keyword(s):  
Insulin Resistance ◽  
Case Control Study ◽  
Polycystic Ovary ◽  
Premenopausal Women ◽  
C Reactive Protein ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Albumin Ratio ◽  
Reactive Protein ◽  
Control Study

ObjectivePolycystic ovary syndrome (PCOS) is an endocrine disorder affecting approximately one in seven women who experience androgen excess, menstrual cycle irregularities, frequent anovulation and a tendency for central obesity and insulin resistance. Chronic subclinical inflammation is now recognised as being common in the context of PCOS, which led to the postulation that PCOS may fundamentally be an inflammatory process. This study aimed to: (1) evaluate serum C reactive protein (CRP)/albumin ratio as a potential predictive biomarker for PCOS; (2) compare the relationship between CRP/albumin and PCOS to variables classically associated with the syndrome.DesignCase–control study.SettingAdult obstetrics/gynaecology, endocrinology and outpatient clinics; university hospital in Bahrain.Participants200 premenopausal women with a diagnosis of PCOS, and 119 ethnically matched eumenorrheic premenopausal women.Main outcome measuresCRP/albumin ratio, anthropometric measures, insulin resistance, androgen excess.ResultsIndependent of body mass index (BMI), receiver operating characteristic curve for CRP/albumin ratio as a selective biomarker for PCOS was 0.865 (95% CI 0.824 to 0.905), which was more sensitive than CRP alone. Binary regression analysis showed that CRP/albumin ratio outperformed classical correlates, Free Androgen Index and insulin resistance, in predicting PCOS for every BMI category.ConclusionCRP/albumin ratio, a marker for inflammation related to metabolic dysfunction, was found to have a stronger association with PCOS than either androgen excess or insulin resistance. Inflammation is known to be influenced by adiposity, but relative to controls, women with PCOS have higher levels of CRP/albumin irrespective of BMI. These findings support the view that inflammation plays a central role in the pathophysiology of PCOS.

scholarly journals In Silico Approaches to Identify Polyphenol Compounds as α-Glucosidase and α-Amylase Inhibitors against Type-II Diabetes

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1877
Author(s):  
Jirawat Riyaphan ◽  
Dinh-Chuong Pham ◽  
Max K. Leong ◽  
Ching-Feng Weng
Keyword(s):  
Natural Products ◽  
In Silico ◽  
Type Ii Diabetes ◽  
Postprandial Glucose ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii ◽  
Amino Acid Residues ◽  
Discovery Studio

Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both α-glucosidase and α-amylase enzymes inhibitors can suppress peaks of postprandial glucose with surplus adverse effects, leading to efforts devoted to urgently seeking new anti-diabetes drugs from natural sources for delayed starch digestion. This review attempts to explore 10 families e.g., Bignoniaceae, Ericaceae, Dryopteridaceae, Campanulaceae, Geraniaceae, Euphorbiaceae, Rubiaceae, Acanthaceae, Rutaceae, and Moraceae as medicinal plants, and folk and herb medicines for lowering blood glucose level, or alternative anti-diabetic natural products. Many natural products have been studied in silico, in vitro, and in vivo assays to restrain hyperglycemia. In addition, natural products, and particularly polyphenols, possess diverse structures for exploring them as inhibitors of α-glucosidase and α-amylase. Interestingly, an in silico discovery approach using natural compounds via virtual screening could directly target α-glucosidase and α-amylase enzymes through Monte Carto molecular modeling. Autodock, MOE-Dock, Biovia Discovery Studio, PyMOL, and Accelrys have been used to discover new candidates as inhibitors or activators. While docking score, binding energy (Kcal/mol), the number of hydrogen bonds, or interactions with critical amino acid residues have been taken into concerning the reliability of software for validation of enzymatic analysis, in vitro cell assay and in vivo animal tests are required to obtain leads, hits, and candidates in drug discovery and development.

scholarly journals Overview of the Role of Glucagon like Peptide-1 Receptor Agonists in the Management of Polycystic Ovary Syndrome

2021 ◽  
pp. 312-318
Author(s):  
Asma Alshenqiti ◽  
Ghaida Almohammadi
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Premenopausal Women ◽  
Ovary Syndrome ◽  
Receptor Agonists ◽  
Long Term Effect ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects premenopausal women. It is a multifactorial disease that involves hyperandrogenism, ovulatory dysfunction, insulin resistance and genetic factors. Women with PCOS present with menstrual disorder, hirsutism, and obesity. Diagnosis of PCOS involves evidence of ovulation dysfunction, hyperandrogenism, either physical or biochemical, and ultrasonographic evaluation of the ovarian morphology. There is no single treatment for PCOS but rather it is a symptom-oriented management. Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) are insulin sensitizers usually involved in the management of PCOS. Aim: This article aims to review the evidence regarding the role GLP-1 RAs in the management of polycystic ovary syndrome. Conclusion: GLP-1 RAs found to improve PCOS outcomes in the form of increasing menstrual frequency, reducing androgens levels, higher pregnancy rates, weight reduction, and improving insulin resistance. Mild and transient adverse events were observed such as nausea, diarrhea, headache, insomnia and mild hypoglycemic events. However, long term studies are required to assess long term effect of GLP-1 RAs and its safety during pregnancy.

scholarly journals The Effect of Berberine on Polycystic Ovary Syndrome Patients with Insulin Resistance (PCOS-IR): A Meta-Analysis and Systematic Review

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Meng-Fei Li ◽  
Xiao-Meng Zhou ◽  
Xue-Lian Li
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Randomized Controlled Trials ◽  
Polycystic Ovary ◽  
Chinese Herbs ◽  
Controlled Trials ◽  
Ovary Syndrome ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Reproductive Endocrine

Purpose. To evaluate the effect of berberine (BBR) on polycystic ovary syndrome (PCOS) patients with insulin resistance (IR). Methods. PubMed (in English), Medline (in English), Embase (in English), CNKI (in Chinese), WanFang DATA (in Chinese), and VIP (in Chinese) were searched for randomized controlled trials in human beings with the search terms including “polycystic ovary syndrome /PCOS” and “berberine/BBR/Huang liansu (in Chinese)/ Xiao bojian (in Chinese)” till July 2018. Relevant indices were collected and analyzed by Stata 13.0. Results. A total of 9 randomized controlled trials were included. Limited data demonstrated the results as follows: No significant difference was found between berberine (BBR) and metformin (MET) on alleviating insulin resistance, improving glycolipid metabolism, or reproductive endocrine condition. MET combined with BBR was not superior to MET alone, but cyproterone acetate (CPA) combined with BBR was superior to CPA alone in improving some of the reproductive endocrine indices. The combination of BBR and Chinese herbs also showed positive effect. However there are insufficient data to make any conclusions on the effect of BBR on PCOS-IR. Conclusion. BBR showed a promising prospect in treating PCOS-IR. But its mechanisms are still unclear, and more properly designed, randomized, double-blind, placebo-controlled trials are needed to further confirm its effect and safety.

scholarly journals Virtual Screening Kandungan Senyawa Kipas Laut (Gorgonia mariae) sebagai Anti-Asma

2020 ◽  
Vol 16 (2) ◽  
pp. 199
Author(s):  
Faruk Jayanto Kelutur ◽  
Resmi Mustarichie ◽  
Abdul Kakhar Umar
Keyword(s):  
Free Energy ◽  
Virtual Screening ◽  
In Silico ◽  
Log P ◽  
P Value ◽  
Amino Acid Residues ◽  
Test Compound ◽  
Discovery Studio ◽  
The People ◽  
Pharmacological Targets

<p>Kipas laut (<em>Gorgonia mariae</em>) telah digunakan masyarakat Maluku secara turun temurun sebagai obat asma. Kandungan metabolit sekunder yang paling dominan dalam kipas laut adalah sterol, dimana memiliki aktivitas terapi melalui efek sinergisme antara senyawa metabolit dengan polivalent activity. Pengujian kipas laut sebagai anti-asma belum pernah dilaporkan sebelumnya. Oleh karena itu, perlu dilakukan virtual screening menggunakan metode in silico pada komponen sterol kipas laut sebagai tahap awal dalam menentukan efektivitas terapi anti-asma dengan memprediksi nilai ikatan energi bebas (ΔG), konstanta inhibisi (Ki), dan interaksi residu asam amino menggunakan Autodock Tools 4.2 dan Discovery Studio 2016 Client®. Keamanan dan efektivitas kandidat obat dievaluasi menggunakan parameter dari Lipinski Rule of Five dan pre-ADMET. Hasil penelitian menunjukkan bahwa konstanta inhibisi dan ikatan energi bebas (Ki; ΔG) dari komponen senyawa kipas laut dapat diurutkan secara potensial yaitu 4,24-dimetil kolestanol  (0,809; -12,40) &gt; 24-metil-22-dehidrokolesterol (0,864; -12,36) &gt; 23-demetil gorgosterol (1,74; -11,95) &gt; 4,24-dimetil-22-dehidrokolestanol (1,89; -11,90). Residu asam amino yang berperan penting dalam aktivitas inhibisi hCHIT1 adalah 213-ASP. Semua komponen senyawa uji memiliki nilai log P lebih dari 5 yang menunjukkan bahwa kelarutan dan toksisitas perlu diperhatikan. Evaluasi distribusi pre-ADMET berdasarkan nilai dari pengikatan protein plasma menunjukan bahwa senyawa uji dapat berdifusi menembus membran plasma dan berinteraksi sesuai target farmakologi. Selain itu, hasil parameter uji toksisitas menunjukkan bahwa senyawa 23-demetil gorgosterol dan 4,24-dimetil-22-dehidrokolestanol memiliki potensi sebagai anti-asma.</p><p><strong>Virtual Screening of the Compounds in Gorgonians </strong><strong>(<em>Gorgonia mariae</em>) as anti-asthma. </strong>The people of Maluku have used Kipas laut (G. mariae) for generations as an asthma medicine. The secondary metabolite that is most dominant in kipas laut is sterols, which have therapeutic activity through the synergistic effect between metabolite compounds and polyvalent activity. Anti-asthma activity of kipas laut has never been reported. Therefore, it is necessary to do virtual screening using the in silico method on the sterol component of kipas laut as a first step in determining the effectiveness of anti-asthma therapy by predicting the value of free energy bonds (ΔG), constant inhibition (K<sub>i</sub>), and interactions of amino acid residues using Autodock Tools 4.2 and Discovery Studio 2016 Client®. The effectiveness and safety of prospective drugs are evaluated using the Lipinski Rule of Five and pre-ADMET. The results showed that the value of inhibition constants and free energy bonds (Ki; ΔG) on the compound of kipas laut that was potentially sorted was 4.24-dimethyl cholestanol (0.809; -12.40) &gt; 24-methyl-22-dehydrocholesterol (0.864; -12.36) &gt; 23-demethyl gorgosterol (1.74; -11.95) &gt; 4.24-dimethyl-22-dehidrokolestanol (1.89; -11.90). The crucial residues of amino acids is 213-ASP, which play a significant role in hCHIT1 inhibitory activity. All components of the test compound have a log P value of more than five, which indicates that solubility and toxicity need to be considered. Evaluation of the pre-ADMET based on the value of plasma protein binding shows that the test compound can diffuse through the plasma membrane and interact according to pharmacological targets. In addition, the results of the toxicity test showed that 23-demethyl gorgosterol and 4.24-dimethyl-22-dehidrokolestanol compounds have potential as anti-asthma.</p>

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