Smooth Muscle Relaxant Activity Research Articles

Spasmolytic Activity of 1,3-Disubstituted 3,4-Dihydroisoquinolines.

This article concerns the spasmolytic activities of some novel 1,3-disubstituted 3,4-dihydroisoquinolines. These compounds can be evaluated as potential therapeutic candidates according to Lipinski's rule of five, showing high gastrointestinal absorption and the ability to cross the blood-brain barrier, which is a very important parameter in the drug discovery processes. In silico simulation predicted smooth muscle relaxant activity for all the compounds. Since smooth muscle contractile failure is a characteristic feature of many disorders, in the current paper, we concentrate on the parameters of the spontaneous contractile responses of smooth muscle (SM) cells compared to the well-known drug mebeverine. Two of the newly synthesized substances can be identified as essential modulating regulators and potentially used as therapeutic molecules. One of these molecules also showed significant DPPH antioxidant activity compared to rutin.

Airways Relaxant and Antiasthmatic Activity of Aconitum heterophyllum Wall ex Royle. Roots: A Mechanistic Insight.

Aconitum heterophyllum Wall ex Royle. (Ranunculaceae) is a traditional medicinal herb that has shown extensive pharmacological potential to treat cough, diarrhea, and infectious diseases but no scientific evidence is available to validate its antiasthmatic potential. In this study, we have investigated the tracheal relaxation and antiasthmatic activity of the selected bioactive fraction of A. heterophyllum. Chemical profiling of the most effective fraction obtained via bioassay-guided fractionation was done using LC-MS (Liquid chromatography-mass spectrometry, a technique utilized in the identification, separation, and quantification of known and unknown compounds). Molecular docking analysis of characterized constituents was performed to recognize the binding receptors, followed by an evaluation of the tracheal relaxation ability of active fraction. An acute oral toxicity study of the most effective fraction was done using OECD guidelines 423. Further, the therapeutic efficacy of the fraction was validated in asthma using a guinea pig model of ovalbumin (OVA) induced allergic asthma. The bio-guided activity revealed that hydro-methanolic extract of A. heterophyllum roots (F-1) was the most active fraction. LC-MS analysis of F-1 showed the presence of six major bioactive compounds in F-1. Molecular docking studies revealed strong binding affinities of identified constituents with histaminic receptor (H1) and muscarinic receptor (M3). The ex vivo study demonstrated smooth muscle relaxant activity of F-1 via dysregulating diverse signal transduction pathways viz. histaminic and muscarinic receptors antagonism (non-competitive), stimulation of β2-adrenergic receptor pathway, and soluble guanylyl cyclase activation. The findings of acute oral toxicity studies revealed that F-1 had no toxicity up to the dose of 2000 mg/Kg. The anti-asthmatic therapeutic efficacy of F-1 was further confirmed by the amelioration of respiratory hyperresponsiveness in asthmatic guinea pigs. This is the first evidence-based study showing the antiasthmatic therapeutic potential of the traditionally used herb A. heterophyllum through, computational and animal studies.

Cedrus deodara (Roxb. ex D.Don) G.Don bark fraction ameliorates metabolic, endocrine and ovarian dynamics in rats experiencing polycystic ovarian syndrome.

In the Ayurvedic system of medicine, Cedrus deodara bark has been utilized as a folk medicine to remove ovarian cysts and treat infertility in females. The present study is the first to investigate ameliorating potential of C. deodara bark on testosterone propionate and high-fat diet-induced polycystic ovarian syndrome in experimental rats. LC-MS analysis of the fraction selected through bioassay-guided approach employing uterine relaxant activity was performed to determine the bioactive constituents present in it. Further, the identified compounds were docked on the catalytic site of the androgen receptor and insulin receptor substrate-1. Later, the fraction was investigated against testosterone propionate and high-fat diet-induced PCOS in rats. Chloroform fraction (F1) of the plant bark was found most active in uterine smooth muscle relaxant activity. LC-MS analysis of F1 indicated the presence of key flavonoids namely deodarin, cedrin, deodardione, and cedrusinin. Afterward, a molecular docking study of these compounds revealed impressive binding interactions with androgen receptor and insulin receptor substrate-1. Besides, in vivo studies, treatment with F1 significantly restored the estrous cycle in rats from the diestrus phase in a dose-dependent manner. Also, the disturbed metabolic and endocrine profile was markedly improved in rats. Later, histopathological analysis revealed the presence of a large number of mature follicles and corpora lutea in F1-treated rats. In a nutshell, F1 exhibited promising beneficial effects in PCOS and associated conditions via amelioration of metabolic, endocrine, and ovarian dynamics in experimental rats.

Design of Multitarget Inhibitors as Tracheal Smooth Muscle Relaxants.

Asthma complications and adverse effects associated with steroidal therapy highlight the need for non-steroidal compounds intercepting asthmatic pathophysiology at multiple targets. The present investigation was carried out to evaluate the tracheal smooth muscle relaxant effect of virtually designed, combinatorially synthesized polyfunctional N-heteroarylamides. Virtual screening and molecular docking studies of designed compounds were performed using PyRx and AUTODOCK 4.2 software against molecular targets viz. FLAP, LTB4, and H1 receptor. Cross-validation of virtual screening results and active site, confirmation was performedusingVlife MDS software version 3.5. The combinatorial approach was used to synthesize designed compounds in which heterocyclic amines were reacted with substituted aromatic acid chlorides by nucleophilic substitution reaction to obtain a 5x5 mini-library. The structures of synthesized leads were confirmed by infrared and proton magnetic resonance spectroscopic analysis. Synthesized compounds were evaluated for their smooth muscle relaxation effect on isolated goat tracheal smooth muscle. Results were calculated as a percent decrease in contraction response observed using histamine and LTB4. The tested compounds produced anticipated tracheal smooth muscle relaxant activity. Based on the results of screening the structure-activity relationships (SAR) have been reported. Present study concluded that synthesized polyfunctional N-heteroarylamides have a tracheal smooth muscle relaxant effect. The mode of action is predicted from the analysis of virtual screening results. A good correlation was observed between virtual screenings and biological activities of lead molecules suggesting the rationale used to optimize the structural requirements of a ligand for selected targets is appropriate.

Investigations of plausible pharmacodynamics supporting the antispasmodic, bronchodilator, and antidiarrheal activities of Berberis lycium Royle. Via in silico, in vitro, and in vivo studies

Ethnopharmacological relevanceBerberis lycium Royle, a member of the Berberidaceae family, is a high-value medicinal plant with a documented history of usage in traditional medicine and has demonstrated significant therapeutic results among local populations throughout the globe. It is used traditionally in many parts of Pakistan to treat diarrhea, abdominal spasms, coughs, and chest problems. Aim of the studyTo investigate the antispasmodic, bronchodilator, and antidiarrheal effects of B. lycium and its possible underlying mechanisms through in silico, in vitro, and in vivo studies. Materials and methodsLC ESI–MS/MS analysis was used to identify bioactive components within the hydromethanolic extract of B. lycium. In silico studies, including network pharmacology and molecular docking, were utilized to investigate the antispasmodic and bronchodilator properties of the extract's bioactive components. In vitro pharmacological studies were conducted using isolated rabbit jejunum, trachea, urinary bladder, and rat ileum preparations. In vivo antidiarrheal activities were conducted in mice, including castor oil-induced diarrhea, intestinal transit, and castor oil-induced enteropooling. ResultsThe LC ESI–MS/MS analysis of the hydromethanolic extract of B. lycium identified 38 bioactive compounds. Network pharmacology study demonstrated that the mechanism of BLR for the treatment of diarrhea might involve IL1B, TLR4, PIK3R1, TNF, PTPRC, IL2, PIK3CD, and ABCB1, whereas, for respiratory ailments, it may involve PIK3CG, TRPV1, STAT3, ICAM1, ACE, PTGER2, PTGS2, TNF, MMP9, NOS2, IL2, CCR5, HRH1, and VDR. Molecular docking research revealed that chlorogenic acid, epigallocatechin, isorhamnetin, quinic acid, gallic acid, camptothecin, formononetin-7-O-glucoside, velutin, caffeic acid, and (S)-luteanine exhibited a higher docking score than dicyclomine with validated proteins of smooth muscle contractions such as CACB2_HUMAN, ACM3_HUMAN, MYLK_HUMAN, and PLCG1_HUMAN. In vitro investigations demonstrated that Blr.Cr, Blr.EtOAc, and Blr.Aq relaxed spontaneously contracting jejunum preparations; carbachol (1 μM)-induced and K+ (80 mM)-induced jejunum, trachea, and urinary bladder contractions in a concentration-dependent manner, similar to dicyclomine. Moreover, Blr.Cr, Blr.EtOAc, and Blr.Aq exhibited a rightward shift in Ca+2 and carbachol cumulative response curves, similar to dicyclomine, demonstrating the coexistence of antimuscarinic and Ca+2 antagonistic mechanisms due to the presence of alkaloids and flavonoids. In vivo antidiarrheal activities showed that the hydromethanolic extract was significantly effective against castor oil-induced diarrhea and castor oil-induced enteropooling, similar to loperamide, and charcoal meal intestinal transit, similar to atropine, in mice at doses of 50, 100, and 200 mg/kg body weight, which supports its traditional use in diarrhea. ConclusionThe dual blocking mechanism of muscarinic receptors and Ca+2 channels behind the smooth muscle relaxing activity reveals the therapeutic relevance of B. lycium in diarrhea, abdominal spasms, coughs, and chest problems.

Starfish smooth muscle relaxing activity of SALMFamide isotype peptide and its analog derived from starfish, Asterias rubens

An organism’s physiological processes and behaviors are regulated by neuropeptides and hormone peptides. The first neuropeptide identified from echinoderms is SALMFamide. The two most well-studied SALMFamide neuropeptides are S1 and S2, which possess myoactivity on apical muscle, tube feet, and the cardiac stomach of starfishes. However, neuropeptide candidates identified from SALMFamide’s precursor protein sequence have not been investigated. This study aims to compare the bioactivity of SALMFamide neuropeptides from the starfish Asterias rubens using various starfish muscle preparations. In this study, the bioactivity of the L-type SALMFamide neuropeptides from the starfish A. rubens, AYHTGLPFamide (SALMFa-A) and the derivative AYHSALMFamide (SALMFa-B) was investigated. The neuropeptides were applied on Asterias amurensis apical muscle, tube feet, which revealed that the neuropeptides exhibit relaxing activity on apical muscle but no activity on tube feet. The native SALMFa- A peptide had lower relaxing activity on the apical muscle compared to the derivative peptide SALMFa-B. The relaxing activity of two neuropeptides also was compared with those on the apical muscle of Patiria pectinifera, which revealed relaxing activity as well as SALMFamide-S1 and S2 neuropeptides. Moreover, the investigation of SALMFa-A and SALMFa-B peptides’ bioactivity on P. pectinifera cardiac stomach muscle also showed slight relaxing activity.

Phytochemical Contents, Biological Activities and Therapeutic Applications of Hedera Helix (Ivy Leaf) Extracts: A Review

Background: Herbs have long been used as natural therapeutics, and recent controlled clinical studies have confirmed some of the presumed benefits. Hedera helix(ivy leaves) is a valuable common form related to the family Araliaceae. Many herbal preparations include extracts from their leaves as the principle active ingredient. Objective: The objective of this article is to summarize the pharmacological activities and phytochemical screening of H. helix. Methods: To prepare this article, the data was collected from different sources, including books, thesis, research and etc. Results: The all-published studies depend on isolation, identification, and characterization of different active constituents of H. helix leaves, followed by the determination of biological activities in vivo and in vitro. Chemical screening has shown that H. helix leaves are a rich source of phytochemicals demonstrating therapeutic activities, such as sterols, tannins, terpenoids, glycosides, phenols, emetine alkaloids, flavonoids, saponins, volatile and fixed oils, vitamins, carbohydrates, reducing sugars, and minerals. Further, studies of disease models and clinical trials have demonstrated anti-inflammatory, analgesic, cough suppressant, expectorant, anticancer, antimicrobial, anticoagulant, and smooth muscle relaxant activities. Conclusion: This review summarizes the bioactive constituents of H. helix leaves and their underlying pharmacological mechanisms, clinical efficacies, and safety profiles. We also suggest potential therapeutic uses for COVID-19.

Ex Vivo and In Vivo Study of Some Isoquinoline Precursors

This article concerns the synthesis and biological activities of some N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides as isoquinoline precursors and compounds with smooth muscle (SM) relaxant activity. Aim: find the biological activity of N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides and compare it with papaverine, an isoquinoline alkaloid that has been known as a brain and coronary vasodilator and SM relaxant. Materials and methods: In silico simulation with the PASS online program predicts SM relaxant activity for the compounds. The amides were tested on the isolated gastric SM preparations (SMPs) from rats to determine their effects on spontaneous contractile activity (CA) compared with papaverine. The in vivo effect on the learning and memory processes of rats was also assessed. Results: the data from the isometric measurements showed that one of the compounds caused ex vivo relaxation in circular SM tissues isolated from the stomach (corpus) of male Wistar rats. Conclusion: We found that the compound’s SM relaxation uses the papaverine pathway. It also has an improving effect on the cognitive functions of learning and memory processes in rats.

BLACK TURMERIC- CURCUMA CAESIA ROXB, AND ITS MEDICINAL PROPERTIES: A REVIEW

Curcuma caesia Roxb., commonly known as black turmeric is an important medicinal plant belonging to the family Zingiberaceae. It is a perennial crop with bluish-black rhizome. The rhizome in inner part is bluish-black in colour and emits a characteristic sweet smell due to the presence of essential oil. It contains: alkaloids, terpenes, amino acids, carbohydrates, tannins, flavones, flavonoids, steroids, reducing sugars, proteins, anthraquinones, glycosides, cardiac glycosides. The rhizomes have a high value because of its putative medicinal properties. The rhizomes are used in carminative properties (Gantait et al., 2011), treatment of smooth muscle relaxant activity, haemorrhoids, leprosy, asthma, cancer, epilepsy, fever, wound, vomiting, menstrual disorder, anthelmentic, aphrodisiac, gonorrhoeal discharges and inflammation (Arulmozhi et al., 2006 and Sasikumar, 2005).

Antispasmodic and antimicrobial activities of pyrazole‐containing ferrocenyl alkanols versus their phenyl analogs, and the entry point to potential multitarget treatment for inflammatory bowel diseases

AbstractInflammatory bowel diseases (IBM), such as Crohn's disease, and their common complications represent a global health challenge. Many pyrazole derivatives, such as the spasmolytic drug metamizole, have already found their place among the frequently used therapeutic agents. Alteration of the structure of established therapeutic drugs by introducing a ferrocene moiety was shown to be a promising way for the discovery of new drugs. Herein, two libraries of analogous ferrocenyl (1a‐1j) and phenyl alkanols (2a‐2j) containing a pyrazole core, among which 17 completely new structures, have been synthesized, and structurally and electrochemically characterized. These compounds, along with the aldehydes used for their synthesis, were tested in parallel for their antispasmodic, acetylcholinesterase‐inhibitory, and antimicrobial activities to evaluate their potential as multitarget IBM drugs. The antispasmodic activity was investigated by assessing their effect on both the amplitude and number of spontaneous contractions of isolated rat ileum. Their antimicrobial effect was evaluated against a panel of Gram‐positive and Gram‐negative bacterial strains and fungi. It was found that several of the evaluated compounds displayed gastrointestinal smooth muscle relaxant activity, among them, 1‐(1H‐3‐ferrocenyl‐1‐phenylpyrazol‐4‐yl)‐3‐methylbutan‐1‐ol (1d) showed a remarkable effect by superseding the activity of papaverine. Together with the fact that it represents one of the most antimicrobially active investigated compounds, 1d is a good candidate for further pharmacological evaluation as a multitarget drug for IBM.

8-Hydroxyquinolin-2(1H)-one analogues as potential β2-agonists: Design, synthesis and activity study.

β2-Agonists that bind to plasmalemmal β2-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their β2-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC50<20 pM) and selective β2-agonists among the compounds tested. They behaved as partial β2-agonists in non-overexpressed HEK293cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary, B05 and C08 are β2-agonists with potential applicability in chronic respiratory diseases.

Evaluation of the Antinociceptive, Antiallodynic, Antihyperalgesic and Anti-Inflammatory Effect of Polyalthic Acid.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly used, but their adverse effects warrant investigating new therapeutic alternatives. Polyalthic acid, a labdane-type diterpenoid, is known to produce gastroprotection, tracheal smooth muscle relaxation, and antitumoral, antiparasitic and antibacterial activity. This study aimed to evaluate the antinociceptive, antiallodynic, antihyperalgesic and anti-inflammatory effect of polyalthic acid on rats. Moreover, the effectiveness of treating hyperalgesia with a combination of polyalthic acid and naproxen was analyzed, as well as the type of drug–drug interaction involved. Nociception was examined by injecting 1% formalin into the right hind paw and thermal hyperalgesia and inflammation by injecting a 1% carrageenan solution into the left hind paw of rats. Allodynia was assessed on an L5/L6 spinal nerve ligation model. Polyalthic acid generated significant antinociceptive (56–320 mg/kg), antiallodynic (100–562 mg/kg), and antihyperalgesic and anti-inflammatory (10–178 mg/kg) effects. Antinociception mechanisms were explored by pretreating the rats with naltrexone, ODQ and methiothepin, finding the effect blocked by the former two compounds, which indicates the participation of opioid receptors and guanylate cyclase. An isobolographic analysis suggests synergism between polyalthic acid and naproxen in the combined treatment of hyperalgesia.

Tea Consumption and Risk of Chronic Obstructive Pulmonary Disease in Middle-Aged and Older Singaporean Adults.

ObjectiveThe anti-oxidant and anti-inflammatory actions of phytochemicals and the smooth muscle relaxant actions of theophylline present in tea may confer pulmonary protection and reduce COPD risk. We investigated tea consumption (black, oolong, or green) association with COPD risks in a population-based cohort study of older adults aged ≥55.MethodsGOLD criteria was used to identify prevalent and incident cases of COPD (FEV1/FVC <0.70) among 4617 participants and 920 participants free of COPD at baseline who were assessed at follow-up 4.5 years later.ResultsPrevalent cases of COPD consumed less tea than their non-COPD counterparts. Estimated odds ratio (OR) and 95% confidence intervals (95% CI) of association with prevalent COPD, adjusted for age, sex, ethnicity, housing type, smoking, alcohol, physical activity and BMI declined across tea consumption levels (p-trend=0.048), and was lowest for ≥3 cups/day (OR=0.77, 95% CI=0.61–0.96). The cumulated incidence of COPD declined across tea consumption categories (p-trend=0.012) and the lowest OR of association (OR=0.35, 95% CI=0.17–0.69) with consuming ≥3 cups/day after co-variate adjustment.ConclusionDifferent kinds of tea showed similar non-significant trends of associations but appeared to be strongest for green tea. Tea consumption in this Asian population was associated with lowered COPD prevalence and incidence.

Chemical composition and uterine smooth muscle relaxant activity of essential oils from 10 kinds of blood-activating and stasis-resolving Chinese medicinal herbs

Ethnopharmacological relevanceDysmenorrhea is one of the most common gynecological problems among menstruating females. Blood-activating and stasis-resolving herbs (BASRHs) have been employed to be the first choice for treating dysmenorrhea in China. Especially, the essential oils of some BASRHs have been confirmed to play important roles in the treatment of dysmenorrhea, but the constituents and uterine smooth muscle relaxant activity of some commonly used BASRH essential oils have not been fully assessed, and whether there are differences in the constituents and anti-dysmenorrhea effect among BASRH essential oils has not been evaluated. Aim of the studyThis study aims to systematically investigate the chemical constituents of 10 BASRH essential oils and assess their uterine smooth muscle relaxant activity and the preliminary mechanism of the most effective essential oil. Materials and methodsThe chemical constituents of 10 BASRH essential oils were analyzed by Gas Chromatography-Mass Spectrometer. A rat model of dysmenorrhea in vitro was established to investigate the uterine smooth muscle relaxant activity of 10 kinds of essential oils. Rat isolated uterus strips were given different dose of 10 kinds of essential oils (0.04, 0.08, 0.16 mg/mL). The contractile responses were recorded with Power Lab recording system, and contractile tension, contractile frequency, and contractile activity were evaluated. The preliminary mechanism of the essential oil of the rhizomes of Curcuma phaeocaulis Valeton (CPEO) was assessed using a rat model of dysmenorrhea in vivo and in vitro, and rats were given the CPEO (15, 30, and 60 mg/kg) by gavage. The level of Ca2+ in uterine tissue of rats was determined by methyl thyme phenol blue colorimetric and Bradford methods. The effects of CPEO on extracellular Ca2+ influx and intracellular Ca2+ release were evaluated using the isolated uterus. ResultsThe results of Gas Chromatography-Mass Spectrometer analysis showed that more than 81 components (content: 1% max appearance) were identified. The main components of the 10 BASRH essential oils were found to be monoterpenoids, sesquiterpenoids, diterpenoids, aromatics, aliphatics, and phthalides. The study of in vitro smooth muscle relaxant activity demonstrated that all the essential oils except the essential oil of the roots of Cyathula officinalis K.C.Kuan markedly decrease the contractile activity, tension, and frequency (P < 0.05 or P < 0.01). Among these oils, CPEO has the most pronounced effect. Further in vivo studies indicated that CPEO can significantly decrease the level of Ca2+ in uterine tissue when compared with the model group (P < 0.05 or P < 0.01). In vitro studies indicated that CPEO can inhibit the extracellular Ca2+ influx and intracellular Ca2+ release in favor of uterine relaxation. ConclusionsBASRH essential oils play an important role in inhibiting uterine smooth muscle contractions, and sesquiterpenoids and phthalides in BASRH essential oils are important active compounds for relaxing uterine smooth muscle. CPEO is a favorable candidate for developing anti-dysmenorrhea drugs.

Synthesis and Modeling Studies of Furoxan Coupled Spiro-Isoquinolino Piperidine Derivatives as NO Releasing PDE 5 Inhibitors.

Nitric oxide (NO) is considered to be one of the most important intracellular messengers that play an active role as neurotransmitter in regulation of various cardiovascular physiological and pathological processes. Nitric oxide (NO) is a major factor in penile erectile function. NO exerts a relaxing action on corpus cavernosum and penile arteries by activating smooth muscle soluble guanylate cyclase and increasing the intracellular concentration of cyclic guanosine monophosphate (cGMP). Phophodiesterase (PDE) inhibitors have potential therapeutic applications. NO hybridization has been found to improve and extend the pharmacological properties of the parental compound. The present study describes the synthesis of novel furoxan coupled spiro-isoquinolino-piperidine derivatives and their smooth muscle relaxant activity. The study reveals that, particularly 10d (1.50 ± 0.6) and 10g (1.65 ± 0.7) are moderate PDE 5 inhibitors as compared to Sidenafil (1.43 ± 0.5). The observed effect was explained by molecular modelling studies on phosphodiesterase.

Tracheal relaxation through calcium channel blockade of Achillea millefolium hexanic extract and its main bioactive compounds

Ethnopharmacological importanceAchillea millefolium L. (Asteraceae) is used for the treatment of respiratory diseases, diabetes, and hypertension. Aimto explore its tracheal relaxant properties and clarify its functional mechanism of action on smooth muscle cells, which allow us to propose it as a potential anti-asthmatic drug. Material and methodsorganic and hydro-alcoholic extracts from A. millefolium were obtained by macerations, then their relaxing effect on ex vivo isolated rat trachea rings was determined. Most active extract (hexanic extract, EHAm) was studied to determine its functional mechanism of action using synergic, antagonist and inhibitor agents related with the contraction/relaxation process of the smooth muscle. Also, EHAm was subjected to bio-guided fractionation by open-column chromatography (on silica gel) using cyclohexane-EtOAc (80:20) in an isocratic way to isolate main bioactive compounds. Resultsorganic and hydro-alcoholic extracts showed relaxant effect in a concentration-response dependent manner, being EHAm the most active. The functional mechanism of action indicates that EHAm induced a non-competitive antagonism to the muscarinic receptors ; in addition, the NO/cGMP pathway is involved in the relaxation process of the tracheal smooth muscle. However, the most important mechanism of action showed by EHAm was related with the calcium channel blockade influx into the smooth muscle cells. On the other hand, epimeric sesquiterpene lactones leucodin (1) and achillin (2) were isolated and purified, which are responsible for the observed smooth muscle relaxant activity of the extract. Conclusionhexanic extract of A. millefollium induced a significant relaxant effect on tracheal rat rings by calcium channel blockade and NO release.

Design, synthesis and biological evaluation of 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one derivatives as potent β2-adrenoceptor agonists

A series of β2-adrenoceptor agonists with an 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one moiety is presented. The stimulatory effects of the compounds on human β2-adrenoceptor and β1-adrenoceptor were characterized by a cell-based assay. Their smooth muscle relaxant activities were tested on isolated guinea pig trachea. Most of the compounds were found to be potent and selective agonists of the β2-adrenoceptor. One of the compounds, (R)-18c, possessed a strong β2-adrenoceptor agonistic effect with an EC50 value of 24 pM. It produced a full and potent airway smooth muscle relaxant effect same as olodaterol. Its onset of action was 3.5 min and its duration of action was more than 12 h in an in vitro guinea pig trachea model of bronchodilation. These results suggest that (R)-18c is a potential candidate for long-acting β2-AR agonists.

Advances in chemical constituents of isoquinoline alkaloids from Nelumbo nucifera and their smooth muscle relaxation effect

Lotus( Nelumbo nucifera) is a traditional medicinal plant,and nowadays it is regarded both as medicine and food. It is widespread across China and rich in natural resources. Almost every part of N. nucifera could be used for medical or edible purpose,including seeds( Lianzi),black ripe fruits( Shilianzi),seed coats( Lianyi),green embryos of mature seed( Lianzixin),flowers( Lianhua),stamens( Lianxu),receptacles( Lianfang),leaves( Heye),leaf or flower stalks( Hegeng),leaf bases( Heyedi),rhizomes( Ou) and rhizome nodes( Oujie). Therefore,this plant is praised as a commercial crop with great economic values. Isoquinoline type alkaloids are the main chemical components of lotus. Smooth muscles usually exist in the digestive tract,respiratory tract and vascular,urinary,reproductive and other human systems. Dysfunction of smooth muscle contraction will induce many diseases including hypertension,asthma and gastrointestinal disorder,etc.,and most of current therapeutic strategies rely on relaxation of smooth muscle by drugs.Previous studies have shown that alkaloids of lotus have strong relaxation activity on smooth muscle. The present paper reviews phytochemistry and smooth muscle relaxation activity of 59 isoquinoline alkaloids from N. nucifera through accessing CNKI,PubMed and multiple databases for biomedical sciences.

Diphenethylpiperidine alkaloids with tracheal smooth muscle relaxation activity from Hippobroma longiflora (L.) G. Don

Phytochemical investigations on the whole plant of Hippobroma longiflora (L.) G. Don have resulted in the isolation and elucidation of three new diphenethylpiperidine alkaloids, hippofoline A (1), hippofoline B (2), and (−)-cis-2′,2′′-diphenyllobelidiol N-oxide (5), alongside two known alkaloids, (−)-lobeline (3) and (−)-cis-2′,2′′-diphenyllobelidiol (4). The absolute configurations of alkaloids 1 and 2 were deduced based on experimental and calculated ECD data as well as biogenetic consideration, while the absolute configurations of alkaloids 3 and 4 in their free base form were confirmed by Cu Kα radiation X-ray diffraction analyses. Alkaloids 2–4 were shown to induce concentration-dependent relaxation effects on rat isolated tracheal rings that were pre-contracted with carbachol.

Does nifedipine improve outcomes of embryo transfer?: Interim analysis of a randomized, double blinded, placebo-controlled trial.

Implantation failure is the main factor affecting the success rate of in vitro fertilization (IVF) procedures. Studies have reported that uterine contractions (UC) at the time of embryo transfer (ET) were inversely related to implantation and pregnancy rate, hence reducing the success of IVF treatments. Various pharmacological agents, with the exception of calcium channel blockers, have been investigated to improve ET outcomes by reducing UC. Thus, a double-blinded randomized, placebo-controlled trial was conducted to determine whether nifedipine, a calcium channel blocker with potent smooth muscle relaxing activity and an excellent safety profile, can improve the outcome of patients undergoing ET treatments. Ninety-three infertile women were recruited into 1 of 2 groups: placebo (n = 47) or nifedipine 20 mg (n = 46). Study participants were admitted 30 minutes prior to ET and given either tablet after their baseline vital signs were recorded. They then underwent ET and were observed for adverse events for another 30 minutes post-ET. Follow up of the participants' outcomes was conducted via electronic medical records. The primary outcomes are implantation and clinical pregnancy rates. Secondary outcomes include any maternal or fetal adverse events, miscarriage, pregnancy, live births, and neonatal outcomes. Resulting data were then analyzed using t test, Pearson chi-square test, and Fisher exact test to compare outcomes between the 2 groups. No statistical differences in the implantation rate (42.6% vs 39.1%, P = .737, rate ratio 0.868, 95% confidence interval [CI]: 0.379-1.986) and the clinical pregnancy rate (23.4% vs 26.1%, P = .764, rate ratio 1.155, 95% CI: 0.450-2.966) were detected between the placebo and the treatment groups. In addition, no statistical significance between the placebo and the treatment groups for any secondary outcomes were detected. This double blinded, randomized, and placebo-controlled trial demonstrated that the single use of 20 mg nifedipine given 30 minutes before embryo transfer did not improve the implantation rate or the clinical pregnancy rate of the infertility treatment. Further studies are required to demonstrate the clinical benefits and risks of nifedipine usage in embryo transfer.