Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome.
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ABSTRACT:
SUBMITTER: Wang Y
PROVIDER: S-EPMC4910093 | biostudies-literature | 2016 Jun
REPOSITORIES: biostudies-literature
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Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome.
Wang Yu Y Fu Xin X Xu Jing J Wang Qiuhong Q Kuang Haixue H
Scientific reports 20160616
Polycystic ovary syndrome (PCOS) is a common multifactorial endocrine disorder among women of childbearing age. PCOS has various and heterogeneous clinical features apart from its indefinite pathogenesis and mechanism. Clinical drugs for PCOS are multifarious because it only treats separate symptoms. Berberine is an isoquinoline plant alkaloid with numerous biological activities, and it was testified to improve some diseases related to PCOS in animal models and in humans. Systems pharmacology wa ...[more]
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Project description:PURPOSE:The therapy of polycystic ovary syndrome (PCOS) is based on synthetic hormones associated with lifestyle changes, but these therapies cannot be taken continuously, especially by women who would like to become pregnant. Thus, nutraceutical compounds were investigated as possible agents for treatment of PCOS. Berberine is shown to be effective against insulin resistance and obesity, particularly against visceral adipose tissue (VAT). Because of these properties, researchers theorized that berberine could be effective in PCOS treatment. METHODS:The aim of this narrative review was to assess the state of the art about the use of berberine in PCOS management. RESULTS:This review included 5 eligible studies. Despite the number of studies considered being low, the number of women studied is high (1078) and the results are interesting. Two authors find out that berberine induced a redistribution of adipose tissue, reducing VAT in the absence of weight loss and improved insulin sensitivity, quite like metformin. One author demonstrated that berberine improved the lipid pattern. Moreover, three authors demonstrated that berberine improved insulin resistance in theca cells with an improvement of the ovulation rate per cycle, so berberine is also effective on fertility and live birth rates. CONCLUSIONS:Finally, berberine is safe to use in premenopausal women who want to get pregnant and showed few side effects in all the cited studies. In conclusion, the use of berberine for PCOS is safe and promising, even if more studies are needed to create a consensus about the dosage of berberine useful for long-term therapy.
| S-EPMC7028834 | biostudies-literature
Project description:BackgroundS. miltiorrhiza-C. aromatica (Danshen-Yujin; red sage and turmeric) is a frequently used Chinese herbal medicine pair in treating polycystic ovary syndrome (PCOS). This study aimed to classify the molecular targets and mechanisms participating in treating PCOS through network pharmacology.MethodsThe Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform was employed for screening the active ingredients of S. miltiorrhiza-C. aromatica. The molecular targets from the UniProt database were identified and compared to the differentially expressed genes (DEGs) in the Gene Expression Omnibus (GEO) dataset GSE34526; the intersecting genes were obtained by constructing a Venn diagram. Protein-protein interaction (PPI) network construction and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were made on the crossover genes. A key protein 3-dimensional (3D) structure was created using the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCDB PDB) database. Finally, the clinical data of 104 hospital-admitted PCOS patients from January 2018 to December 2020 were retrospectively analyzed to explore and analyze the clinical value of S. miltiorrhiza-C. aromatica in treating PCOS.ResultsIn the TCMSP database, we found a total of 80 active ingredients in S. miltiorrhiza-C. A high clustering and three key proteins were obtained A high-scoring cluster and 3 key proteins, AOAH, HCK, and C1orf162, were obtained through the construction of protein mutual aid network and module analysis of differential genes. KEGG and GO enrichment analyses indicated that the S. miltiorrhiza-C. aromatica treatment mechanism in PCOS was mainly involved with inflammation-related pathways. The clinical data of PCOS patients were retrospectively analyzed. In the end, The long diameter of the ovary, the thickness of the endometrium, and the antral follicle count in the combined treatment group of S. miltiorrhiza-C. aromatica combined with clomiphene were higher after treatment than before treatment, and the clinical symptoms and hormone levels were also improved.ConclusionsThis study expounds the research value of S. miltiorrhiza-C. aromatica in treating PCOS from the perspectives of active ingredients, targets, signaling pathways, and clinical research. These findings also provide an important reference for treating PCOS with traditional Chinese medicine (TCM).
| S-EPMC9951011 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of fertile age. Obesity is encountered in 30-70% of PCOS-affected women, and its presence significantly modifies both clinical and laboratory expression of the syndrome. Obesity increases the risk of co-morbidities associated with PCOS, such as impaired glucose tolerance and type 2 diabetes mellitus, hyperlipidemia and arterial hypertension. The etiopathogenesis of obesity in PCOS has not yet been exactly clarified. There clearly is a vicious circle of abdominal obesity, insulin resistance, and hyperadrogenemia. Differences in ghrelin and neuropeptide Y levels between PCOS patients and those with simple obesity were also described. Weight loss is the first choice recommendation for the treatment of clinical manifestations of PCOS, such as menstrual cycle irregularities, infertility or hirsutism. However, the best treatment approach in obese PCOS patients remains to be defined. Studies concerning different weight loss regimens, antiobesity drugs, bariatric surgery, insulin sensitizers, and hormonal therapy are reviewed.
| S-EPMC6444522 | biostudies-literature
Project description:The etiology of polycystic ovary syndrome (PCOS) has been difficult to determine because its features are heterogeneous, and its origin may also be heterogeneous. Twin studies suggest that its etiology is strongly heritable and genetic approaches are rapidly uncovering new regions of the genome that appear to confer risk for PCOS. Recent genome-wide association studies in Han Chinese women with PCOS demonstrate 11 genetic loci that are associated with PCOS. The variants identified are in regions that contain genes important for gonadotropin action, genes that are associated with risk for type 2 diabetes, and other genes in which the relationship to PCOS is not yet clear. Replication studies have demonstrated that variants at several of these loci also confer risk for PCOS in women of European ethnicity. The strongest loci in Europeans contain genes for DENND1A and THADA, with additional associations in loci containing the LHCGR and FSHR, YAP1 and RAB5/SUOX. The next steps in uncovering the pathophysiology borne out by these loci and variants will include mapping to determine the causal variant and gene, phenotype studies to determine whether these regions are associated with particular features of PCOS and functional studies of the causal variant to determine the direct cause of PCOS based on the underlying genetics. The next years will be very exciting times as groups from around the world come together to further elucidate the genetic origins of PCOS.
| S-EPMC4066994 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is a highly complex endocrine disorder, characterized by hyperandrogenemia, menstrual irregularities and polycystic ovaries. A strong genetic component to the etiology of PCOS is evident. However, due to the genetic and phenotypic heterogeneity of PCOS and the lack of insufficiently large cohorts, studies to identify specific contributing genes to date have yielded only few conclusive results. In this review we discuss the current status of the genetic analysis of PCOS including the results of numerous association studies with candidate genes involved in TGF-β and insulin signaling, type 2 diabetes mellitus and obesity susceptibility. Furthermore, we address current challenges in genetic studies of PCOS, and the promise of new approaches, including genome-wide association studies and next-generation sequencing.
| S-EPMC3609918 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the "thrifty" phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS.
| S-EPMC4499527 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder of premenopausal women worldwide and is characterized by reproductive, endocrine, and metabolic abnormalities. The clinical manifestations of PCOS include oligomenorrhea or amenorrhea, hyperandrogenism, ovarian polycystic changes, and infertility. Women with PCOS are at an increased risk of suffering from type 2 diabetes; me\tabolic syndrome; cardiovascular events, such as hypertension, dyslipidemia; gynecological diseases, including infertility, endometrial dysplasia, endometrial cancer, and ovarian malignant tumors; pregnancy complications, such as premature birth, low birthweight, and eclampsia; and emotional and mental disorders in the future. Although numerous studies have focused on PCOS, the underlying pathophysiological mechanisms of this disease remain unclear. Mitochondria play a key role in energy production, and mitochondrial dysfunction at the cellular level can affect systemic metabolic balance. The recent wide acceptance of functional mitochondrial disorders as a correlated factor of numerous diseases has led to the presupposition that abnormal mitochondrial metabolic markers are associated with PCOS. Studies conducted in the past few years have confirmed that increased oxidative stress is associated with the progression and related complications of PCOS and have proven the relationship between other mitochondrial dysfunctions and PCOS. Thus, this review aims to summarize and discuss previous and recent findings concerning the relationship between mitochondrial dysfunction and PCOS.
| S-EPMC6698037 | biostudies-literature
Project description:BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disease of the female reproductive system that seriously affects women's health. Berberine (BBR) has many pharmacological properties and is used as an insulin sensitizer. This study aimed to investigate the effect of BBR on PCOS and explore its related mechanisms.MethodsForty-two rats were randomly divided into the following six groups (n = 7 per group): control, control + BBR, PCOS-normal diet (ND), PCOS-ND + BBR, PCOS-high-fat diet (HFD), and PCOS-HFD + BBR. The PCOS rat models were established by injecting rats with dehydroepiandrosterone. Further, the rats were gavaged with BBR (150 mg/kg/d) for 6 weeks. Then, the body weight, HOMA-IR, and testosterone levels of all rats were determined. Cell apoptosis of ovary granulosa cells was determined by a TUNEL assay kit. Real-time quantification PCR (RT-qPCR) and western blotting were utilized to evaluate the expression of TLR4, LYN, PI3K, Akt, NF-kB, TNF-α, IL-1, IL-6, and caspase-3.ResultsBBR reduced the levels of insulin resistance and testosterone in PCOS rats. Additionally, the cell apoptosis rate increased significantly in PCOS rats (P < 0.05) and decreased after BBR treatment (P < 0.05). The results of RT-qPCR and western blotting showed that the expression levels of TLR4, LYN, PI3K, Akt, NF-kB, TNF-α, IL-1, IL-6, and caspase-3 significantly increased in PCOS rats, while BBR suppressed their expression levels.ConclusionsBBR may relieve PCOS pathology and IR values by inhibiting cell apoptosis and by regulating the expression levels of TLR4, LYN, PI3K, Akt, NF-kB, TNF-α, IL-1, IL-6, and caspase-3.
| S-EPMC7789273 | biostudies-literature
Project description:ObjectiveTo study the role of selected serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome (PCOS).MethodsSelected serum inflammatory cytokines were analyzed in the particle cells, which were interfered by berberine, from 78 infertile women who were to be treated with In Vitro Fertilization (IVF) /Intracytoplasmic Sperm Injection-Embryo Transfer (icsi-et). Among them, 49 patients had PCOS infertility, and 29 were non-PCOS patients whose infertility resulted from fallopian tube and male factors. The elisa method was used to detect the changes in the expression levels of inflammatory factors in the cells. The correlations between the serum inflammatory cytokine expression levels and the corresponding clinical hormones were analyzed. The changes in the expression (mRNA and protein) levels of the serum inflammatory cytokines were studied by real-time quantitative PCR and protein printing. Fluorescence microscope and flow cytometry were used to detect the glucose uptake capacity of ovarian granulosa cells in PCOS patients under the action of insulin after berberine.ResultsIn the PCOS group, IL-17a (P = 0.001), IL-1Ra (P<0.0001), and IL-6 (P = 0.035) were significantly higher than those in the non-PCOS group. In the non-PCOS group, AMH level was negatively correlated with inflammatory cytokines IL-17a (r = -0.819;P = 0.004), IL-1a (r = -0.716;P = 0.0.02), IL-1b (r = -0.678;P = 0.031), IL-2 (r = -0.765;P = 0.01), and IL-8 (r = -0.705;P = 0.023). However, in the PCOS group, AMH levels were not significantly correlated with the levels of the examined inflammatory cytokines. Berberine significantly reduced the expression level of mTOR mRNA (P = 0.001), and increased the expression level of IRS-1 mRNA (P = 0.009) in the PCOS granule cells.ConclusionIn this study, we find that the elevated levels of serum inflammatory factors IL-17a, IL-1Ra, and IL-6 cause women to be in a subclinical inflammatory state for a long time. Abnormal changes in inflammatory factors alter their original negative correlations with AMH levels, thereby weakening the metabolism of glycolipids, promoting insulin resistance, destroying the normal ovulation and fertilization system of women, leading to polycystic ovary syndrome characterized by menstrual thinning and abnormal ovulation. Berberine can improve the sensitivity of insulin by regulating the signal pathway of insulin receptor substrate-1 (IRS-1) and mammalian target of rapamycin (mTOR) in PCOS patients and achieve a therapeutic effect of treating PCOS.
| S-EPMC7423132 | biostudies-literature
Project description:Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on pelvic scanning. Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease. Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated. In this paper, we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS.This is a multicenter, randomized, placebo-controlled and double-blind trial. A total of 120 patients will be enrolled in this study and will be randomized into two groups. Berberine or placebo will be taken orally for 12 weeks. The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp.We postulate that women with PCOS will have improved insulin resistance following berberine administration.This study is registered at ClinicalTrials.gov, NCT01138930.
| S-EPMC3722087 | biostudies-literature