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      Uterine contractility of plants used to facilitate childbirth in Nigerian ethnomedicine

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          Abstract

          Ethnopharmacological relevance

          Pregnant women in Nigeria use plant preparations to facilitate childbirth and to reduce associated pain. The rationale for this is not known and requires pharmacological validation.

          Aim of study

          Obtain primary information regarding the traditional use of plants and analyze their uterine contractility at cellular level.

          Materials and methods

          Semi-structured, open interviews using questionnaires of traditional healthcare professionals and other informants triggered the collection and identification of medicinal plant species. The relative traditional importance of each medicinal plant was determined by its use-mention index. Extracts of these plants were analyzed for their uterotonic properties on an in vitro human uterine cell collagen model.

          Result

          The plants Calotropis procera, Commelina africana, Duranta repens, Hyptis suaveolens, Ocimum gratissimum, Saba comorensis, Sclerocarya birrea, Sida corymbosa and Vernonia amygdalina were documented and characterized. Aqueous extracts from these nine plants induced significant sustained increases in human myometrial smooth muscle cell contractility, with varying efficiencies, depending upon time and dose of exposure.

          Conclusion

          The folkloric use of several plant species during childbirth in Nigeria has been validated. Seven plants were for the first time characterized to have contractile properties on uterine myometrial cells. The results serve as ideal starting points in the search for safe, longer lasting, effective and tolerable uterotonic drug leads.

          Graphical abstract

          Pregnant woman in Nigeria rely on traditional herbal medicine to induce or ease labor, and to treat childbirth-related complications. Nine plant species have been documented and characterized for their uterotonic properties.

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          Most cited references15

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          Natural products in drug discovery and development.

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            New Insights into Cardiac and Brain Sodium Channels Modulation by Beta Blockers

            Beta-adrenergic blocking agents known as beta blockers are widely used in clinical practice to treat several cardiovascular disorders such as hypertension and high blood pressure in general. They are also used as cardioprotective agents in post myocardial infarction, for the treatment of cardiac arrhythmias and were reported to be beneficial in treating migraine. Recently, they were shown to be efficacious in treating patients with several types of congenital long QT syndromes and in patient with catecholaminergic polymorphic ventricular tachycardia. They mainly act by antagonizing the effects of norepinephrine released from sympathetic nerve endings on beta adrenoceptors. A direct interaction with ion channels in addition to the beta blocking property is now becoming more and more accepted in the scientific community. Propranolol is the beta blocker prototype, it is commonly used as racemic mixture with equal concentrations of R-(+)- and S-(−)-enantiomers. Although, they have been classified as class II antiarrhythmic drugs by Vaughan Williams the molecular mechanisms by which they act is not fully elucidated. On the other hand, their beneficial effect in preventing migraine is not well understood. Earlier electrophysiological studies have reported the effects of propranolol on heart rate and conduction properties in frog auricular fibers, rat, and canine ventricular myocytes. Recent data have shown that beta blockers could modulate Nav1.5, the cardiac voltage-gated sodium channels, but the effect on the expressed brain sodium channels was not envisaged. In the paper by Wang et al., the authors studied the effect of propanol on heterologously expressed recombinant human cardiac (Nav1.5) and the three brain (Nav1.1, Nav1.2, and Nav1.3) sodium channels using whole-cell patch clamp recordings. Previous work from the author's group showed that racemic propranolol and R-(+)-propranolol block Nav1.5 channels (Wang et al., 2008). In this paper the authors extended their study to evaluate the molecular mechanism of the reported block. Both R-(+) and S-(−) propranolol block Nav1.5 sodium channels in tonic and phasic (use-dependent or frequency-dependent) manner with similar affinities. However, nadolol a non-selective beta blocker and metoprolol a selective beta 1 blocker did not induce any tonic or phasic block, suggesting that the sodium channel block property is not common to all beta blockers. More detailed biophysical studies from the authors revealed that that R-(+)-propranolol exhibits biophysical effects on Nav1.5 that are similar but not identical to lidocaine, the class 1 antiarrhythmic drug prototype. That R-(+)-propranolol acts as a typical local anesthetic and class 1 antiarrhythmics on sodium channels by interacting with specific residues in the DIV-S6 segment, including the phenylalanine-1760, known to play a central role in drug binding (Ragsdale et al., 1994) and therefore shares this property with established antiarrhythmic drugs. Finally, further detailed biophysical study from the authors showed that the brain sodium channels (Nav1.1, Nav1.2, and Nav1.3) exhibit less sensitivity to R-(+)-propranolol than the Nav1.5 channels. Since the phenylalanine-1760 is a conserved residue in all sodium channels, including brain sodium channels, studies to elucidate the basis of this reduced affinity at molecular level are warranted. These data reported by Wang et al., in this issue of Frontiers in Pharmacology of Ion Channel and Channelopathies, will pave the path toward a more understanding of the effect of beta blockers on sodium channels, a widely used class of drugs.
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              Telomerase immortalization of human myometrial cells.

              Several strategies have been described for the primary culture of human myometrial cells. However, primary cultures of myometrial cells have a limited life span, making continual tissue acquisition and cell isolation necessary. Recent studies have demonstrated that cell culture life span is related to chromosomal telomere length, and cellular senescence results from progressive telomere shortening and the lack of telomerase expression. Transfection of cells with expression vectors containing the human telomerase reverse transcriptase (hTERT) maintains telomere length and effectively gives normal cells an unlimited life span in culture. In addition, hTERT extends the life span of cultured cells far beyond normal senescence without causing neoplastic transformation. In the present study, we developed a cell line from hTERT-infected myometrial cells (hTERT-HM). Cells were isolated from myometrial tissue obtained from women undergoing hysterectomy, and retroviral infection was used to express the catalytic subunit of telomerase in myometrial cells. Cells expressing hTERT have been in continuous culture for >10 mo, whereas the control culture senesced after approximately 2 mo. Telomerase activity was monitored in cells with a polymerase chain reaction-based telomerase activity assay. Telomerase-expressing cells contained mRNA for alpha smooth muscle actin, smoothelin, oxytocin receptor, and estrogen receptor alpha, but the estrogen receptor beta receptor was lost. Immunoblotting analysis identified the expression of calponin, caldesmon, alpha smooth muscle actin, and oxytocin receptor. Although estrogen receptor expression was below the level of detection with immunoblotting, transfection experiments performed with reporter constructs driven by estrogen response elements demonstrated estrogen responsiveness in the hTERT-HM. In addition, treatment of hTERT-HM with oxytocin caused a concentration-dependent increase in intracellular calcium levels, confirming the presence of functional oxytocin receptors. Myometrial cells immortalized with hTERT retained markers of differentiation that are observed in primary cultures of smooth muscle cells. The expression of various smooth muscle/myometrium cell markers suggests that these cells may be an appropriate model system to study certain aspects of human myometrial function.
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                Author and article information

                Journal
                J Ethnopharmacol
                J Ethnopharmacol
                Journal of Ethnopharmacology
                Elsevier Sequoia
                0378-8741
                1872-7573
                30 August 2012
                30 August 2012
                : 143
                : 1
                : 377-382
                Affiliations
                [a ]Medical University of Vienna, Center for Physiology and Pharmacology, Schwarzspanierstr. 17, A-1090 Vienna, Austria
                [b ]Department of Pharmacognosy, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria
                [c ]National Centre for Biomedical and Engineering Science, National University of Ireland, Galway, Ireland
                Author notes
                [* ]Corresponding author. Tel.: +43 1427762511; fax: +43 142779623. christian.w.gruber@ 123456meduniwien.ac.at
                [1]

                These authors contributed equally to the work.

                Article
                JEP7559
                10.1016/j.jep.2012.06.042
                3430860
                22766472
                fb8e2c73-0e82-4282-80d2-3abf06611139
                © 2012 Elsevier Ireland Ltd.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 14 March 2012
                : 14 May 2012
                : 24 June 2012
                Categories
                Ethnopharmacological Communication

                Pharmacology & Pharmaceutical medicine
                um, use-mentions,postpartum care,htert-hm, human uterine myometrial smooth muscle cells,labor,uterus contractility,maternal healthcare

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