Spasmolytic Effect of Grewia asiatica Fruit Extract on Isolated Smooth Muscles is Mediated via Multiple Pathways

Background. Grewia asiatica Linn, or phalsa, is a commonly consumed fruit in Pakistan. The fruit is employed in the traditional medicine practice of Pakistan as a smooth muscle relaxant in different gastrointestinal (GI) and cardiovascular diseases. In this investigation, we show the antispasmodic and vasorelaxant actions of Grewia asiatica fruit extract. Methods. A 70% methanolic crude extract of the plant material was prepared (Ga.Cr). Different isolated GI tissue preparations and endothelium-intact aortas from rats were utilized to observe the pharmacological actions of the extract. Results. Ga.Cr, in increasing concentrations, inhibited the spontaneously contracting rabbit jejunum. In an effort to determine the mechanism of this relaxant action, contractions were induced in jejunum and ileum tissues with K+ (80 mM). Ga.Cr was able to only partially inhibit these induced contractions indicating that the mechanism might not be completely through a blockade of Ca2+ channels (CCB). When tested on low K+-(25 mM) sustained contractions, Ga.Cr cumulatively suppressed these contractions (0.1–10 mg/ml), indicating an opening of K+ channels (KCO) as the mechanism. Cromakalim, a standard KCO, was also more specific in blocking low K+-induced contractions. For the effect in aorta tissues, Ga.Cr suppressed the agonist-induced contractions from 0.3 mg/ml to 10 mg/ml. Upon challenge with L-NAME, a nitric oxide (NO) blocker, the extract response curve shifted right, indicating vasodilation was mediated via endothelial NO. Conclusion. This study shows that GI antispasmodic and vasodilator activities of Ga.Cr may be mediated via a KCO mechanism in the GI tract and through the release of NO from vascular endothelium.

Effects of Allium cepa and Its Constituents on Respiratory and Allergic Disorders: A Comprehensive Review of Experimental and Clinical Evidence

The health benefits of Allium cepa (A. cepa) have been proclaimed for centuries. Various pharmacological and therapeutic effects on respiratory, allergic, and immunologic disorders are shown by A. cepa and its constituents. Flavonoids such as quercetin and kaempferol, alk(en)yl cysteine sulfoxides including S-methyl cysteine sulfoxide and S-propyl cysteine sulfoxide, cycloalliin, thiosulfinates, and sulfides are the main compounds of the plant. A. cepa displays broad-spectrum pharmacological activities including antioxidant, anti-inflammatory, antihypertensive, and antidiabetic effects. Our objective in this review is to present the effects of A. cepa and its constituents on respiratory, allergic, and immunologic disorders. Different online databases were searched to find articles related to the effect of A. cepa extracts and its constituents on respiratory, allergic, and immunologic disorders until the end of December 2020 using keywords such as onion, A. cepa, constituents of A. cepa, therapeutic effects and pharmacological effects, and respiratory, allergic, and immunologic disorders. Extracts and constituents of A. cepa showed tracheal smooth muscle relaxant effects, indicating possible bronchodilator activities or relieving effects on obstructive respiratory diseases. In experimental animal models of different respiratory diseases, the preventive effect of various extracts and constituents of A. cepa was induced by their antioxidant, immunomodulatory, and anti-inflammatory effects. The preventive effects of the plant and its components on lung disorders induced by exposure to noxious agents as well as lung cancer, lung infection, and allergic and immunologic disorders were also indicated in the experimental and clinical studies. Therefore, this review may be considered a scientific basis for development of therapies using this plant, to improve respiratory, allergic, and immunologic disorders.

The Possible Therapeutic Effects of Some Medicinal Plants for Chronic Cough in Children

The use of plants or their isolated bioactive components for the prevention and treatment of various disorders has been developed. Here, we aim to identify effective medicinal plants for relief of cough and respiratory symptoms in children. The data of this review article were obtained from published articles in scientific databases, including PubMed, Google Scholar, and Scopus, until December 2019. The keywords, including “Zataria multiflora Boiss.” OR “Portulaca oleracea L.” OR “Ferula assa-foetida L.” OR “Nigella sativa L.” AND “respiratory symptoms” OR “airway inflammation” OR “smooth muscle relaxant effects,” were searched individually or combined. The mentioned medicinal plants decreased total white blood cell (WBC), neutrophils, and eosinophils counts of blood and lung lavage in animal model-induced respiratory disorders. These plants also have protective effects on serum immunoglobulin, antibody titer, eosinophil count, and proinflammatory cytokines. Evidence from the studies indicated that the abovementioned medicinal plants have smooth muscle relaxant properties (bronchodilator effects) via stimulation of β-adrenoceptor or inhibition of muscarinic receptors (in vitro) and also improved the pulmonary function test in clinical settings. These medicinal plants are safe and easy to use. Based on the anti-inflammatory, anti-antispasmodic, and immunomodulatory effects, the clinical benefit may be assumed, therefore considering a place for these medicinal plants in relieve of chronic cough and symptoms of children’s allergy, asthma, and common cold.

Molecular mechanism of BK channel activation by the smooth muscle relaxant NS11021

Large-conductance Ca2+-activated K+ channels (BK channels) are activated by cytosolic calcium and depolarized membrane potential under physiological conditions. Thus, these channels control electrical excitability in neurons and smooth muscle by gating K+ efflux and hyperpolarizing the membrane in response to Ca2+ signaling. Altered BK channel function has been linked to epilepsy, dyskinesia, and other neurological deficits in humans, making these channels a key target for drug therapies. To gain insight into mechanisms underlying pharmacological modulation of BK channel gating, here we studied mechanisms underlying activation of BK channels by the biarylthiourea derivative, NS11021, which acts as a smooth muscle relaxant. We observe that increasing NS11021 shifts the half-maximal activation voltage for BK channels toward more hyperpolarized voltages, in both the presence and nominal absence of Ca2+, suggesting that NS11021 facilitates BK channel activation primarily by a mechanism that is distinct from Ca2+ activation. 30 µM NS11021 slows the time course of BK channel deactivation at −200 mV by ∼10-fold compared with 0 µM NS11021, while having little effect on the time course of activation. This action is most pronounced at negative voltages, at which the BK channel voltage sensors are at rest. Single-channel kinetic analysis further shows that 30 µM NS11021 increases open probability by 62-fold and increases mean open time from 0.15 to 0.52 ms in the nominal absence of Ca2+ at voltages less than −60 mV, conditions in which BK voltage sensors are largely in the resting state. We could therefore account for the major activating effects of NS11021 by a scheme in which the drug primarily shifts the pore-gate equilibrium toward the open state.

Design and synthesis of alverine-based ionic liquids to improve drug water solubility

Alverine [3-phenyl-N-(3-phenylpropyl)-N-ethylpropan-1-amine] is a widely known smooth muscle relaxant used to relieve cramps or spasms of the stomach and intestines.

Programmed labour compared with expectant management: is it truly a need of new millennium?

Background: The mechanism triggering the initiation of human parturition is still an enigma. At term a series of complex physiological, biochemical and physical processes cascade resulting in delivery of the fetus. This study deals exclusively with comparison of normal labour, induction of labour with prostaglandin, and with augmentation by intracervical insertion of PGE2 tablets, amniotomy and smooth muscle relaxant. Advantages and disadvantages of each of the above methods are compared with expectant management of labour. Aim of this study was to compare pros and cons of programmed labour that to with expectant management.Methods: Study was conducted in Department of Obstetrics and Gynaecology, Bharati Hospital and Research Centre, Pune. It was a prospective randomized clinical trial. 100 pregnant full term women, were selected for each group. At 0 hour primiprost tablet is inserted into the vagina close to the cervix. Frequency of repetition of tablet will be at three hours interval. Patient will be monitored.Results: The youngest one being of age 17 years and the eldest being of age 29 years. In this, we observed those primi and 2nd gravida patients 2-2 tablets each in latent phase and 1-1 tablets in active phase. The induction delivery Interval in primigravida was observed to be of average of 9 hours. While in II Gravida was 6.5 hours, in III Gravida 5.5 hours and in IV Gravida 4 hours.Conclusions: It has been proved beyond doubt that by programmed labour, the patient definitely can get the benefit of decrease in duration of labour.

Pharmacological Studies Pertaining to Smooth Muscle Relaxant, Platelet Aggregation Inhibitory and Hypotensive Effects of Ailanthus altissima

Objective. This in vitro and in vivo study was conducted to rationalize some of traditional medicinal uses of Ailanthus altissima in gastrointestinal, respiratory, and cardiovascular systems. Materials. Crude extract of Ailanthus altissima (Aa.Cr) and its fractions were prepared and utilized in in vitro and in vivo studies. For in vitro studies, Aa.Cr was investigated on isolated rabbit jejunum, isolated tracheal strip, and isolated aorta of rat suspended in tissue organ bath. Platelet rich and platelet poor plasma were used to study platelet aggregation inhibitory activity. In vivo antidiarrheal effect of Aa.Cr was investigated on balb/c mice pretreated with castor oil to induce diarrhea and SD rats were used to study hypotensive activity. Results. Concentration dependent spasmolytic effects of Aa.Cr and its DCM fraction (Aa.DCM) were observed on spontaneous and spasmogen induced contractions in jejunum isolated from rabbit, but effect against high potassium (high-K+) induced contractions was more potent. Moreover Aa.Cr showed parallel shifting of calcium response curve to the right side. While its aqueous fraction (Aa.aq) caused spasmogenesis of isolated rabbit jejunum, this effect was blocked partially with prior administration of atropine (1μM). Concentration dependent protection against castor oil induced diarrhea was also observed. Relaxant effect was observed by the application of Aa.Cr and Aa.DCM against high-K+ and carbachol (CCh) induced contractions in tracheal strips isolated from SD rats, while Aa.Aq caused partial relaxation of high-K+ induced contractions, but no effect was observed against CCh induced contractions. Relaxation of rat aorta by the application of Aa.Cr and its fractions was also observed. Inhibition of force of contraction in rabbit atrium was also observed. Inhibition of platelet aggregation was observed against epinephrine and ADP induced aggregation. Conclusion. Keeping in view the observed results, it is concluded that smooth muscle relaxant, platelet aggregation inhibitory and hypotensive effect may be due to the blockage of calcium channels.