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Phytochemistry Feb 2022Seven undescribed pregnane glycosides named amurensides A-G and two known aglycones were isolated from the whole herb of Adonis amurensis Regel & Radde. Their structures...
Seven undescribed pregnane glycosides named amurensides A-G and two known aglycones were isolated from the whole herb of Adonis amurensis Regel & Radde. Their structures were established based on 1D and 2D NMR spectroscopic analyses, high-resolution mass spectrometry, and acid hydrolysis. The cytotoxicity of all compounds against three tumor cell lines (HepG2, Caco-2, and A549) were evaluated. Among them, amurensides A-C and E showed moderate inhibitory effects on the growth of HepG2 cells, with IC values ranging from 15.6 to 48.7 μM (sorafenib, 7.5 ± 1.9 μM). Amurensides A、D and F displayed inhibitory effects on the growth of A549 cells with IC values of 18.8 ± 1.2, 12.4 ± 0.6, and 30.4 ± 0.1 μM (cis-platinum, 6.1 ± 0.1 μM), respectively.
Topics: Adonis; Caco-2 Cells; Glycosides; Humans; Pregnanes
PubMed: 34875526
DOI: 10.1016/j.phytochem.2021.113046 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2023Despite the proven importance of neurosteroids in many physiological processes, their role in the pathogenesis of the most of psychiatric disorders remains relatively... (Review)
Review
Despite the proven importance of neurosteroids in many physiological processes, their role in the pathogenesis of the most of psychiatric disorders remains relatively understudied. This article reviews the current clinical evidence on the effects of neurosteroids on the formation and treatment of anxiety disorder, depression, bipolar disorder, and schizophrenia. In particular, the article points out the ambivalent nature of the effects of neurosteroids on GABA- and other receptors. We are especially interested in the anxiolytic and anxiogenic effects of some neurosteroids, the antidepressant effect of allopregnanolone in treating postpartum and other forms of depression, and the nature of short- and long-term mechanisms of antidepressant effects of neurosteroids of different types. The currently unproven hypothesis about the effect of changes in the level of neurosteroids on the course of bipolar disorder is also discussed, with an analysis of the scientific evidence on the development of schizophrenic symptomatology in relation to changing neurosteroid levels in the context of positive and cognitive symptoms.
Topics: Female; Humans; Neurosteroids; Mental Disorders; Bipolar Disorder; Anxiety Disorders; Pregnanolone
PubMed: 37084362
DOI: 10.17116/jnevro202312304131 -
Der Internist Jan 2022Autonomous cortisol secretion was mentioned for the first time in 2016 in the European Guideline on the management of adrenal incidentalomas. (Review)
Review
BACKGROUND
Autonomous cortisol secretion was mentioned for the first time in 2016 in the European Guideline on the management of adrenal incidentalomas.
OBJECTIVES
Review of the state of knowledge on diagnosis, epidemiology, co-morbidities, mortality and treatment of autonomous cortisol secretion in comparison to non-hormone producing adenomas. Recommendation for clinical practice based on the current European guideline.
MATERIALS UND METHODS
Analysis of relevant clinical studies, discussion of basic literature and expert opinions.
RESULTS AND CONCLUSIONS
Autonomous cortisol secretion is a term used to describe abnormal cortisol secretion diagnosed by a pathological 1‑mg dexamethasone suppression test in patients with adrenal incidentaloma, but without clinical manifestation of overt Cushing's syndrome. It is associated with increased mortality and morbidity, especially hypertension, diabetes mellitus type II, dyslipidemia and obesity. Adrenalectomy, as the only specific therapy option, should be considered in an interdisciplinary tumour board.
Topics: Adrenal Gland Neoplasms; Artifacts; Dexamethasone; Humans; Hydrocortisone; Laboratories
PubMed: 34709420
DOI: 10.1007/s00108-021-01188-6 -
Natural Product Research Nov 2021Two new pregnane alkaloids, (20)-20-cinnamoylamino-3-dimethylamino-5-en-pregnane () and (20)-20-cinnamoylamino-3-dimethylamino-pregnane (), and four known alkaloids...
Two new pregnane alkaloids, (20)-20-cinnamoylamino-3-dimethylamino-5-en-pregnane () and (20)-20-cinnamoylamino-3-dimethylamino-pregnane (), and four known alkaloids (+)-(20)-20-(dimethylamino)-3-(3'-isopropyl)-lactam-5-pregn-2-en-4-one (), axillaridine A (), pachysamine M () and 20-dimethylamino-16-hydroxy-3-senecioylamino-pregn-5-ene () were obtained from the whole herb of Sieb. et Zucc. Their structures were determined by various spectral techniques and computed electronic circular dichroism (ECD) data. Compounds were tested for cytotoxicity against three human tumor cell lines and a human umbilical vein endothelial cell (HUVEC) line. Compound exhibited moderate cytotoxicity against MCF-7, U251 and A549 cells with IC values of 15.01 ± 0.47 μM, 20.13 ± 1.34 μM and 20.04 ± 1.16 μM, respectively; compounds showed weak cytotoxic activity against three tumor cells.
Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Humans; Pachysandra; Plant Extracts; Pregnanes
PubMed: 32208773
DOI: 10.1080/14786419.2020.1744143 -
The Journal of Clinical Endocrinology... Oct 2023There is no early, first-trimester risk estimation available to predict later (gestational week 24-28) gestational diabetes mellitus (GDM); however, it would be...
CONTEXT
There is no early, first-trimester risk estimation available to predict later (gestational week 24-28) gestational diabetes mellitus (GDM); however, it would be beneficial to start an early treatment to prevent the development of complications.
OBJECTIVE
We aimed to identify early, first-trimester prediction markers for GDM.
METHODS
The present case-control study is based on the study cohort of a Hungarian biobank containing biological samples and follow-up data from 2545 pregnant women. Oxidative-nitrative stress-related parameters, steroid hormone, and metabolite levels were measured in the serum/plasma samples collected at the end of the first trimester from 55 randomly selected control and 55 women who developed GDM later.
RESULTS
Pregnant women who developed GDM later during the pregnancy were older and had higher body mass index. The following parameters showed higher concentration in their serum/plasma samples: fructosamine, total antioxidant capacity, testosterone, cortisone, 21-deoxycortisol; soluble urokinase plasminogen activator receptor, dehydroepiandrosterone sulfate, dihydrotestosterone, cortisol, and 11-deoxycorticosterone levels were lower. Analyzing these variables using a forward stepwise multivariate logistic regression model, we established a GDM prediction model with a specificity of 96.6% and sensitivity of 97.5% (included variables: fructosamine, cortisol, cortisone, 11-deoxycorticosterone, SuPAR).
CONCLUSION
Based on these measurements, we accurately predict the development of later-onset GDM (24th-28th weeks of pregnancy). Early risk estimation provides the opportunity for targeted prevention and the timely treatment of GDM. Prevention and slowing the progression of GDM result in a lower lifelong metabolic risk for both mother and offspring.
Topics: Female; Humans; Pregnancy; Cortisone; Desoxycorticosterone; Diabetes, Gestational; Fructosamine; Hydrocortisone; Pregnancy Trimester, First; Case-Control Studies
PubMed: 37247379
DOI: 10.1210/clinem/dgad301 -
International Ophthalmology Jan 2023To compare the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAID), corticosteroid (CS), and a combination of both drugs to prevent cystoid macular... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
To compare the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAID), corticosteroid (CS), and a combination of both drugs to prevent cystoid macular edema (CME) after cataract surgery.
METHODS
We searched Pubmed, Cochrane Library, and Embase electronic databases to assess the relevant randomized controlled trials (RCTs) up to 28 April 2021. Network meta-analysis was registered on PROSPERO (CRD42020182520).
RESULTS
Twenty-four RCTs were included in this review. The NSAID and combination of both drugs were significantly reduced the risk of developing CME than CS alone in non-diabetics and mix populations. In the ranking profiles, the combination therapy showed a significant advantage over the single drugs and was less likely to develop CME. Diclofenac was the most likely to reduce the odds of developing CME compared with bromfenac and nepafenac. Dexamethasone was the most likely to reduce the odds of developing CME compared with betamethasone and fluorometholone.
CONCLUSION
NSAID combination with CS has significantly reduced the risk of developing CME postoperatively than the single drug. Diclofenac was superior to bromfenac and nepafenac in preventing CME. Dexamethasone was superior to betamethasone and fluorometholone in preventing CME.
Topics: Humans; Macular Edema; Fluorometholone; Diclofenac; Cataract Extraction; Treatment Outcome; Anti-Inflammatory Agents, Non-Steroidal; Adrenal Cortex Hormones; Dexamethasone; Betamethasone; Cataract
PubMed: 36065039
DOI: 10.1007/s10792-022-02426-y -
Natural Product Research Oct 2021In our search for anti-inflammatory constituents from Vietnamese plants, the methanolic extract of was found to exhibit inhibitory effect on LPS-induced NO production...
In our search for anti-inflammatory constituents from Vietnamese plants, the methanolic extract of was found to exhibit inhibitory effect on LPS-induced NO production in RAW264.7 cells. Phytochemical investigation of this plant led to isolation of four sulphated flavones (), including one new compound 5,3',4'-trihydroxy-7-methoxy-8--sulphate flavone (), and two pregnane-type steroids ( and ), including one new compound 7--heligenin B (). Their structures were elucidated by 1D and 2D NMR as well as HR-QTOF-MS experiments. Among isolated compounds, heligenin B () exhibited potent inhibitory effect on LPS-induced NO production in RAW264.7 cells with IC of 1.23 ± 0.05 µM. The activity of was comparable to that of the positive control cardamonin.
Topics: Flavones; Malvaceae; Molecular Structure; Phytochemicals; Pregnanes; Sulfates
PubMed: 31821052
DOI: 10.1080/14786419.2019.1700253 -
Archives of Gynecology and Obstetrics Sep 2023Retrospectively analyze the clinical characteristics of patients with nonclassical 21-hydroxylase deficiency (NC21OHD) as well as the relationship between the gene...
PURPOSE
Retrospectively analyze the clinical characteristics of patients with nonclassical 21-hydroxylase deficiency (NC21OHD) as well as the relationship between the gene mutations and endocrine hormones. In addition, the relationship between different basal 17-hydroxyprogesterone (17OHP) levels and patients' glucolipid metabolism, hormone levels, pregnancy, and treatment outcomes were examined.
METHODS
Clinical data of 78 females with NC21OHD from January 2012 to July 2022 in the Department of Endocrinology and Metabolism of the Third Affiliated Hospital of Guangzhou Medical University were retrospectively analyzed. Diagnosis was based on the 17OHP level combined with clinical manifestations, imaging, and other endocrine hormones and the cytochrome P450 c21, steroid 21-hydroxylase (CYP21A2) gene.
RESULTS
The age at diagnosis of the 78 patients was 29.1 ± 4.2 years; 83.3% (65/78) of the patients had menstrual abnormalities, 70 patients were of childbearing age, and 97.1% (68/70) had a history of infertility with a median time of infertility of 3.6 years. Moreover, 71.8% (56/78) of the patients had polycystic ovaries, 26.9% (21/78) had hyperandrogenemia manifestations on physical examination, 66.7% (52/78) had adrenal hyperplasia, 32.1% (25/78) had combined dyslipidemia, and 41.0% (32/78) had combined insulin resistance. Pathogenic mutations were detected in 78.2% (61/78) of the patients with both CYP21A2 alleles; 14.1% (11/78) of the patients had only one allele and 7.7% (6/78) had no pathogenic mutations. The levels of total testosterone (TT), progesterone (P) (0 min, 30 min), and 17-OHP (0 min, 30 min, 60 min) in the adrenocorticotropic hormone (ACTH) stimulation test varied between the groups. Furthermore, patients with NC21OHD were divided into 17OHP < 2 ng/ml, 2 ng/ml < 17OHP < 10 ng/ml, and 17OHP ≥ 10 ng/ml groups according to their different basal 17OHP levels. The 17OHP ≥ 10 ng/ml group had significantly higher TT, FT4, basal and post-stimulation progesterone, and 17OHP, net value added of 17-hydroxyprogesterone (△17OHP), net value added of 17-hydroxyprogesterone/net value added of cortisol ratio (△17OHP/△F), the incidence of adrenal hyperplasia, and number of gene mutations compared to those of the 17OHP < 2 ng/ml group (P < 0.05). NC21OHD infertile patients who received low-dose glucocorticoids showed a significant increase in pregnancy and live birth rates, and a significant decrease in miscarriage rate (all P < 0.05).
CONCLUSION
Comprehensive analysis is important as NCCAH diagnoses may be false positive or false negative based on clinical characteristics, hormone levels, and gene detection. Females with NC21OHD showed varying degrees of fertility decline; thus, low doses of glucocorticoid treatment for infertile females with NC21OHD can improve fertility and fertility outcomes.
Topics: Female; Humans; Aged, 80 and over; Young Adult; Adult; Progesterone; Hyperplasia; Retrospective Studies; 17-alpha-Hydroxyprogesterone; Hydrocortisone; Infertility; Steroid 21-Hydroxylase
PubMed: 36773044
DOI: 10.1007/s00404-023-06946-5 -
Molecules (Basel, Switzerland) May 2020A concise synthesis of (16,20)-3β-hydroxy-5α-pregnane-20,16-carbolactam from tigogenin via the corresponding lactone is described. The most efficient synthetic route...
A concise synthesis of (16,20)-3β-hydroxy-5α-pregnane-20,16-carbolactam from tigogenin via the corresponding lactone is described. The most efficient synthetic route consisted of the lactone ring-opening with aminoalane reagent followed by PDC or Dess-Martin oxidation. The oxo-amide obtained was subjected to cyclization with EtSiH/TFA or EtSiH/Bi(TfO). Alternately, the lactone was converted first to the oxo-acid, which was then subjected to the microwave-assisted reductive amination. -Alkyl derivatives were also obtained in a similar way.
Topics: Cyclization; Lactones; Oxidation-Reduction; Pregnanes
PubMed: 32443910
DOI: 10.3390/molecules25102377 -
Hippocampus Jul 2022The ability of endogenous neurosteroids (NSs) with pregnane skeleton modified at positions C-3 and C-5 to modulate the functional activity of inhibitory glycine...
The ability of endogenous neurosteroids (NSs) with pregnane skeleton modified at positions C-3 and C-5 to modulate the functional activity of inhibitory glycine receptors (GlyR) and ionotropic ɣ-aminobutyric acid receptors (GABA R) was estimated. The glycine and GABA-induced chloride current (I and I ) were measured in isolated pyramidal neurons of the rat hippocampus and in isolated rat cerebellar Purkinje cells, respectively. Our experiments demonstrated that pregnane NSs affected I and I in a different manner. At low concentrations (up to 5 μM), tested pregnane NSs increased or did not change the peak amplitude of the I , but reduced the I by decreasing the peak amplitude and/or accelerating desensitization. Namely, allopregnanolone (ALLO), epipregnanolone (EPI), pregnanolone (PA), pregnanolone sulfate (PAS) and 5β-dihydroprogesterone (5β-DHP) enhanced the I in Purkinje cells. Dose-response curves plotted in the concentration range from 1 nM to 100 μM were smooth for EPI and 5β-DHP, but bell-shaped for ALLO, PA and PAS. The peak amplitude of the I was reduced by PA, PAS, and 5α- and 5β-DHP. In contrast, ALLO, ISO and EPI did not modulate it. Dose-response curves for the inhibition of the I peak amplitude were smooth for all active compounds. All NSs accelerated desensitization of the I . The dose-response relationship for this effect was smooth for ALLO, PA, PAS and 5β-DHP, but it was U-shaped for EPI, 5α-DHP and ISO. These results, together with our previous results on NSs with androstane skeleton, offer comprehensive overview for understanding the mechanisms of effects of NSs on I and I .
Topics: 5-alpha-Dihydroprogesterone; Animals; Chlorides; Glycine; Neurons; Neurosteroids; Pregnanes; Pregnanolone; Rats; Rats, Wistar; Receptors, GABA-A; gamma-Aminobutyric Acid
PubMed: 35703084
DOI: 10.1002/hipo.23449