scholarly journals Modulation of ex-vivo uterine contraction by the methanol leaf extract of Alchornea laxiflora Benth. (Euphorbiaceae) and preliminary spectrometric identification of associated secondary metabolites

Author(s):  
Enitome E. Bafor ◽  
Juliet K. Nwogu ◽  
Uloma B. Elvis-Offiah ◽  
Fabian Amaechina ◽  
Josephine Ofeimun ◽  
...  

Background: The leaves of Alchornea laxiflora are traditionally used in the south of Nigeria to prevent preterm births. Aim: This study was designed to investigate the activity of A. laxiflora on uterine contractility. Setting: The leaves of the plant were collected from forests in Egor, Benin City, Nigeria. Methods: The leaves were cleaned and extracted in methanol. The extract (0.005 mg/mL–3.5 mg/mL) was tested on spontaneous uterine contraction and on oxytocin-induced contraction in normal and Ca2+-free media. The plant extract (0.0035 mg/mL, 0.035 mg/mL, 0.35 mg/mL and 3.5 mg/mL) was tested on high KCl-induced uterine contractions (80 mM). The plant extract (3.5 mg/mL) was also studied in the presence of amiodarone and glibenclamide in separate experiments. Mass spectrometric analysis was additionally performed on the plant extract in order to identify significant secondary metabolites that may have contributed to the activity of the plant. Results: The plant extract inhibited spontaneous, oxytocin and high KCl-induced uterine contractions and also significantly inhibited (p < 0.01) oxytocin-induced uterine contraction in Ca2+-free medium. The plant extract significantly inhibited (p < 0.01 and p < 0.05) oxytocin’s amplitude in the presence of amiodarone and glibenclamide, respectively. Secondary metabolites belonging to classes of fatty acids, glycols, terpenes, flavonoid glycosides and porphyrins were identified. Conclusion: Alchornea laxiflora inhibited mouse uterine contractility possibly through interaction with potassium and calcium channels. Of the known metabolites identified, 3-deoxy-arabino-hept-2-ulosonic acid, 17-hydroxyingenol and phaeophorbide-a methyl inhibit uterine contractility and may contribute to the activity of A. laxiflora in utero.

Author(s):  
Enitome E. Bafor ◽  
Wellington O. Omokaro ◽  
Osamuyi H. Uwumarongie ◽  
Uloma B. Elvis-Offiah ◽  
Osemelomen Omoruyi ◽  
...  

Background: The plant Dryopteris filix-mas has been used traditionally for its uterine-stimulant effects.Aim: The current study is therefore aimed at investigating and determining the effect of the leaves of D. filix-mas on uterine contractility in vitro.Setting: Fresh leaves of D. filix-mas were collected from a river bank in the south-western part of Nigeria.Methods: The leaves of D. filix-mas were cleaned, dried and extracted in methanol. The extract (0.07 µg/mL–21.0 µg/mL) was tested on the isolated mouse uteri in order to determine activity on spontaneous-induced uterine contractions. Subsequently the extract (0.005 mg/mL and 0.05 mg/mL) was tested on oxytocin-induced contraction (0.00017 ng/mL–4.98 ng/mL) in calcium-containing media, submaximal oxytocin-induced contraction (0.116 ng/mL) in calcium-free media and in the presence of high KCl-induced uterine contractions (80 mM). The extract was also subjected to mass spectrometric determination of secondary metabolites.Results: The plant extract inhibited spontaneous-induced contractions with IC50 amplitude = 658.41 ng/mL ± 0.11 ng/mL and IC50 frequency = 175.32 ng/mL ± 0.53 ng/mL. The plant extract inhibited oxytocin-induced and high KCl-induced uterine contractions (p < 0.01 at 0.5 mg/mL). The plant extract had no effect on oxytocin-induced contractions under calcium-free conditions. Secondary metabolites belonging to classes of fatty acids, alkaloids, saponin glycosides, amino acids, limonoids, terpenes and porphyrins were identified.Conclusion: The current study reports an inhibitory effect of the plant on uterine contractility in this study, suggesting possible application as a tocolytic or as a contraceptive, as most contraceptive plants have shown uterine-relaxing effect.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Rees ◽  
Y Huang ◽  
M Akhtar ◽  
M Mischi ◽  
A Humberstone ◽  
...  

Abstract Study question What is the effect of nolasiban on the uterine contractility of in-vitro fertilisation (IVF) patients prior to embryo transfer (ET) ? Summary answer A single oral dose of nolasiban 900 mg administered 4 h before ET significantly decreased contraction frequency and increased coordination compared to placebo. What is known already Nolasiban is an investigational oral oxytocin receptor antagonist (OTRa) being developed to improve the chance of pregnancy following ET. Increased uterine contraction frequency can influence embryo implantation, and the coordination of these uterine contractions is equally important. OTRa have been shown to decrease uterine contractions and increase endometrial perfusion. Recently, an automated and quantitative measurement tool using transvaginal ultrasound (TVUS) to better characterise uterine contractility has been developed which can be used to quantify the effect of nolasiban on uterine contractility. Study design, size, duration This study is part of a completed multi-centre randomised placebo-controlled trial (IMPLANT 1 – NCT02310802) in IVF patients (n = 247) carried out in 2015. Our study retrospectively assessed a sub-set of patients with good quality TVUS recordings to evaluate their mechanical uterine motion that were randomised to receive either nolasiban 900mg (n = 39) or placebo (n = 42). Participants/materials, setting, methods Subjects were &lt; 37 years, undergoing ET on Day 3 following IVF/ICSI and with evidence of uterine contractions 4 h before ET. Nolasiban was administered 4 h before ET. Patients underwent TVUS immediately before drug administration and again immediately before ET. Uterine contraction frequency, amplitude, power and coordination were measured by applying dedicated speckle tracking and strain analysis. The Shapiro–Wilk test, followed by the Wilcoxon rank-sum test were applied to compare features between treatment groups. Main results and the role of chance The mean (SD) frequency of uterine contractions was 1.54 (0.25) in the nolasiban group versus 1.57 (0.12) in the placebo group (p = 0.016). The mean (SD) coordination was 0.10 (0.17) in the nolasiban group versus 0.02 (0.16) in the placebo group (p = 0.034). The coordination feature was measured by assessing the presence of simultaneous movements of the anterior and posterior uterine walls, a higher value reflects increased coordination. There was no difference in contraction amplitude or power. Limitations, reasons for caution This was a retrospective analysis of TVUS videos. The small sample size limits the generalisability of the findings. Furthermore, our initial results do not show how the changes in uterine motion may affect pregnancy rate after ET, meaning that the clinical relevance of our results remains to be proven. Wider implications of the findings: Our results show that in patients taking one 900mg dose of nolasiban prior to ET, beneficial uterine contractions are seen, which could be promising for embryo implantation and pregnancy in IVF patients. Our quantitative TVUS measurement tool can be applied to different patient populations to accurately quantify uterine motion. Trial registration number NCT02310802


2020 ◽  
Vol 27 (2) ◽  
pp. 108-118
Author(s):  
E.E. Bafor ◽  
G.U. Omogiade

There is a need to develop new drugs from natural products for the safe and effective management of female reproductive disorders. This research was therefore aimed at the investigation of two commonly consumed natural products on uterine function. The ex vivo uterine activity of Theobroma cacao aqueous seed extract and Cymbopogon citratus aqueous leaf extract was investigated on non pregnant mouse uteri. The effect of T. cacao (0.1 mg/mL) and C. citratus (0.1 mg/mL) on spontaneous uterine contractility and in the presence of oxytocin (11.54 nM) was examined. This study showed that T. cacao elicited a significant increase (p < 0.05) in the amplitude of spontaneous uterine contractions with no significant ch ange in the frequency, which was similarly observed with C. citratus leaf extract. An increase in amplitude and frequency of oxytocin induced uterine  contractions was observed in the presence of T. cacao while with C. citratus there was a significant (p< 0.05) reduction in amplitude and non significant reduction in frequency of oxytocin induced uterine contractions. The uterotonic effect of both extracts in the absence of agonists observed maybe as a result of constituents with agonistic activity on intra cellular calcium. This study has shown that T. cacao and C. citratus could stimulate uterine activity and may therefore be useful in the management of uterine contractility disorders. Keywords : Theobromacacao Cymbopogoncitratus , uterus, spontaneous contractions


Author(s):  
Beata Modzelewska ◽  
Marcin Jóźwik ◽  
Tomasz Kleszczewski ◽  
Stanisław Sulkowski ◽  
Maciej Jóźwik

Objective: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. Design: This was a controlled and prospective ex vivo study. Setting: The work was conducted as a collaboration between 4 academic departments. Materials and Methods: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. Results: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). Limitations: These results require now to be placed into a firm clinical context. Conclusions: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.


Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 887
Author(s):  
Yun-Ju Huang ◽  
Yu-Chieh Chen ◽  
Hsin-Yuan Chen ◽  
Yi-Fen Chiang ◽  
Mohamed Ali ◽  
...  

Dysmenorrhea is one of the most prevalent disorders in gynecology. Historically, adlay (Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been explored for its anti-tumor, pain relief, anti-inflammatory, and analgesic effects. The aim of this study was to evaluate the effects of adlay seeds on the inhibition of uterine contraction and thus dysmenorrhea relief, in vitro and in vivo. HPLC-MS and GC were used to elucidate the ethyl acetate fraction of adlay testa ethanolic extract (ATE-EA) and ethyl acetate fraction of adlay hull ethanolic extract (AHE-EA). Elucidation yielded flavonoids, phytosterols, and fatty acids. Uterine leiomyomas and normal adjacent myometrial tissue were evaluated by oxytocin- and PG-induced uterine contractility. ATE-EA and AHE-EA suppressed uterine contraction induced by prostaglandin F2 alpha (PGF2α), oxytocin, carbachol, and high-KCl solution ex vivo. In addition, the external calcium (Ca2+) influx induced contraction, and increased Ca2+ concentration was inhibited by ATE-EA and AHE-EA on the uterine smooth muscle of rats. Furthermore, ATE-EA and AHE-EA effectively attenuated the contraction of normal human myometrium tissues more than adjacent uterine leiomyoma in response to PGF2α. 3,5,6,7,8,3′,4′-Heptamethoxyflavone and chrysoeriol produced a remarkable inhibition with values of IC50 = 24.91 and 25.59 µM, respectively. The experimental results showed that treatment with ATE-EA at 30 mg/day effectively decreased the writhing frequency both on the oxytocin-induced writhing test and acetic acid writhing test of the ICR mouse.


2018 ◽  
Vol 26 (7) ◽  
pp. 988-996
Author(s):  
Bryan F. Mitchell ◽  
Mei Chi ◽  
Elle Surgent ◽  
Bailey M. Sorochan ◽  
Curtis N. Tracey ◽  
...  

Background: Preterm birth is the most common cause of neonatal morbidity and mortality and a common precedent to lifelong disability. Current treatment has minimal efficacy. Objective: We assessed the role of isozymes of the protein kinase C (PKC) family in regulating the phosphorylation of myosin regulatory light chains (RLCs), which regulate uterine contractility. We also explored the mechanisms through which these isozymes function. Study Design: We used a previously characterized and validated quantitative in-cell Western (ICW) assay to measure site-specific phosphorylations on myosin RLC and CPI-17. Cultures of human uterine myocytes (hUM) were treated with the potent contractile stimulant oxytocin to induce uterine contractility or a pharmacological mimic of diacyl-glycerol to stimulate the conventional and novel isozymes of the PKC family. Combinations of isozyme-selective inhibitors were used to determine the effects of the conventional and novel classes of isozymes. Results: Stimulation of PKC using phospho-dibutyrate caused immediate, concentration-dependent inhibition of uterine activity ex vivo. Using the ICW assay with hUM, the oxytocin-stimulated increase in the pro-contractile phosphorylations of myosin RLCs at serine19 and threonine18 was completely inhibited by prior treatment with phorbol-12-myristate-13-acetate, which stimulates both convention and novel classes of isozymes. Our results suggest that the conventional class of isozymes cause a reduction in phosphorylations at serine19 and threonine18 by reducing activity of myosin light chain kinase. The novel class of isozymes has 2 mechanisms of action: the first is activation of CPI-17 through phosphorylation at threonine38, which results in reduced activity of myosin light chain phosphatase and increased levels of activated myosin RLC; the second is increased phosphorylation of the N-terminal region of myosin RLC. Conclusions: Specific agonists for the conventional isozymes or inhibitors of the novel isozymes of the PKC family could be useful pharmacological agents for regulation of uterine activity.


2010 ◽  
Vol 17 (01) ◽  
pp. 84-90
Author(s):  
FARZANA LATIF ◽  
BUSHRA BANO ◽  
UZMA HUSSAIN

Objective: To compare the efficacy of Glyecryl trinitrate patch for prolonging gestation for more than 48 hours, 7 days or upto 37 weeks of gestation with Salbutamol in preterm labour. Study Design: Compartive descriptive study. Setting: Fatima Memorial HospitalLahore. Period: Dec 2003 to Jan 2005. Patients & Methods: The study was carried out on 60 pregnant patients admitted in hospital with thesymptoms and signs of preterm labour. The results were statistically analyzed using SPSS version 8.0. Results: Two groups (TransdermalGlyceryl Trinitrate group and Salbutamol) comprising 30 patients each were made. In Glyceryl Trinitrate group, transdermal patch was appliedand in Salbutamol group,. Intravenous infusion titrated according to frequency, duration and intensity of uterine contractions. All the patientsin each group were evaluated for prolongation of gestation for 48 hours till 37th week of gestation. The mean prolongation of pregnancy was26 days in GTN group and 32 days in Salbutamol group. The decrease in frequency of uterine contractions by 67.51 ± 7.74% in first 48 hoursof applying transdermal Glyceryl Trinitrate patch and by 80.14 ± 8.43 % in Salbutamol group which was statistically significant. Conclusion:Trinitrate appears to be a safe, well tolerated and non-invasive but less effectives method of suppressing uterine contraction in preterm labouras compared to Salbutamol.


1970 ◽  
Vol 18 (1) ◽  
pp. 75-78
Author(s):  
S Ishrat ◽  
F Islam

Although misoprostol is widely used in Obstetrics and Gynaecology it is not officially approved for these uses. The literature review shows its efficacy and safety in most of its indications. Misoprostol is effective in cervical priming and inducing uterine contraction and so used in termination of pregnancy. Its use at term can be complicated with serious side effects on uterine contractility and fetal heart rate , rarely causing uterine rupture and fetal death. But review of the studies finds limited reports of these life-threatening complications. Misoprostol is also effective in prevention of postpartum haemorrhage but the effect is not more than combination of oxytocin and ergometrine. Key words: Misoprostol; prostaglandin; clinical use. DOI: 10.3329/jdmc.v18i1.6311 J Dhaka Med Coll. 2009; 18(1) : 75-78


2019 ◽  
Vol 21 (5) ◽  
pp. 495-499
Author(s):  
Rebecca Benfield ◽  
Du Feng ◽  
Jan Salstrom ◽  
Melydia Edge ◽  
Denise Brigham ◽  
...  

Background: The first stage of labor is significantly longer with epidural analgesia use, implying an alteration in uterine contractility. Although the pre-epidural fluid bolus is used with every epidural and affects as many as 80% of laboring women, its effects on uterine contraction parameters are unknown. Design: Using a retrospective descriptive repeated measures design, we compared uterine contraction parameters including frequency, duration, peak intensity, resting tone, and Montevideo units at baseline and during the intravascular pre-epidural fluid bolus (Bolus) epochs for healthy laboring women at term gestation undergoing augmentation or induction. Method: Contraction parameters were compared using data from fetal monitor strips with intrauterine pressure catheter instrumentation. Results: No significant differences were found between epochs for women receiving constant Pitocin dosages ( n = 10) using Wilcoxon signed rank tests at .05 α level, but all parameters trended in the direction of improved contractility except frequency, which was unchanged. Conclusions: These pilot study findings do not support the proposal that the pre-epidural fluid bolus is a contributor to decreased uterine contractility in any parameter. It is possible that the bolus improved myometrial perfusion and metabolic function in the contracting and resting states in less hydrated women.


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