Muscle Relaxant Properties Research Articles

Paradoxical Agitation and Masseter Spasm During Propofol Procedural Sedation: A Case Report

Introduction: Propofol is an anesthetic agent commonly used in emergency department (ED) procedural sedation. It is often preferred in orthopedic procedures because of its muscle-relaxing properties. Rarely, however, it can induce agitation and muscle hypertonicity. Case Report: A 58-year-old man presented to the ED with a left ankle fracture-dislocation. Propofol was used to facilitate procedural sedation, but the patient became mildly agitated. Ketamine was used to achieve full induction, after which propofol was used again to facilitate muscle relaxation. Near the end of the procedure, the patient had opisthotonos and masseter spasm requiring bag-valve-mask ventilation and subsequent intubation. This reaction was ultimately attributed to adverse effects of the propofol. Conclusion: While propofol is generally well tolerated, it can potentially cause agitation, hypertonicity, and other side effects such as muscle spasms and seizure-like activity. Acknowledging and preparing for these risks can potentially improve patient outcomes.

Antipyretic effect of oral dipyrone (Metamizole) compared to oral ibuprofen in febrile children: a systematic review and meta-analysis

BackgroundDipyrone (Metamizole) is a potent pain reliever and fever reducer with muscle relaxant properties, most commonly used as an analgesic and antipyretic agent. Despite the fact that it has been banned in many high-income countries following confirmed studies of fatal agranulocytosis and adverse drug reactions, it is still widely used in various countries of the world. However, the antipyretic therapeutic indications of dipyrone in febrile children are currently unknown, and there is little information on the advantages and disadvantages of using dipyrone in febrile children. In febrile children, we expected that dipyrone’s antipyretic effectiveness wouldn’t be any more effective than ibuprofen. Therefore, the purpose of this research is to evaluate the effectiveness of oral dipyrone and oral ibuprofen as antipyretics in febrile children.MethodsSeveral databases, including PubMed, Scopus, Web of Science, and Cochrane Library, were searched thoroughly using a pre-established search strategy for potential research. The studies included in this analysis comprised randomized controlled trials that compared the antipyretic effects of oral ibuprofen and oral dipyrone in febrile children. Data analysis was carried out using RevMan 5.4 software.ResultsThree studies were selected among the 27 publications we discovered to be applicable, and they underwent qualitative and quantitative analysis. The pooled analysis revealed no discernible difference between oral dipyrone and oral ibuprofen in terms of their antipyretic effects (Mean difference (MD) = 0.06; 95% confidence interval (CI): -0.08, 0.20).ConclusionBoth oral dipyrone and ibuprofen are effective in reducing high-temperature levels in febrile children without any significant difference.

A Comparative Study of Skeletal Muscle Relaxant Effects of Thiocolchicoside, Diazepam and Their Combination in Wistar Rats Using the Rotarod Apparatus.

Introduction Thiocolchicoside (THC) is a semi-synthetic derivative of colchicoside and anaturally occurring compound in the seeds of the Gloriosa Superba L.plant. At present, it is used as a skeletal muscle relaxant. It is used to treat rheumatic arthritis, orthopaedic conditions, and trauma. Topically, it is used to relieve excruciating spasms in the muscles.It is also used to treat a wide range of conditions, which include surgical pain, cervicobrachial neuralgia, acute to chronic torticollis, Parkinson's disease, drug-induced Parkinsonism,spastic hemiplegia, tooth soreness,acute lower back pain, etc. THC is used in conjunction with non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and analgesics.By downregulating and inhibiting the synthesis of NF-κB-regulated gene products, it possesses anti-inflammatory properties. To prevent aneuploidy, the European Medical Agency has placed restrictions on the use of THC, stating that it should not be injected for five days or taken orally for longer than seven days. This is because its metabolism in the body may lead to the production of the metabolite M2. When used during pregnancy, the growing fetus is more negatively impacted. It has also been connected to infertility in men. Aim To study the skeletal muscle relaxant effects of THCin Wistar rats in comparison with standard drugs. Materials and methods The skeletal muscle relaxant activity level was measured using the rotarod apparatus. There were five groups of Wistar rats (n = 6). Group I received 0.9% normal saline (NS) as a control. Group II (test group) received THC 2 mg/kgintraperitoneally (ip).Group III (test group) received THC 4 mg/kg (ip). Group IV diazepam (DIZ) 3 mg/kg (ip) which is the standard treatment group.Group V received a combination of THC 2 mg/kg and DIZ 3 mg/kg. After treatment, retention time was noted at intervals of 30, 60, and 120 minutes. Results Group I (control), Group II (THC 2 mg/kg) and Group III (THC 4 mg/kg) did not demonstrate any skeletal muscle relaxant activity. Group IV (DIZ 3 mg/kg) and Group V (THC 2 mg/kg + DIZ 3 mg/kg) showed statistically significant skeletal muscle relaxant activity when compared to control. However, there was no statistically significant difference between the skeletal muscle relaxant activity of these two groups. This indicates that the addition of THC did not potentiate the skeletal muscle relaxant activity of DIZ. Conclusion THC didn't show skeletal muscle relaxant properties in both doses and did not potentiate the activity of DIZ.

Isolation and characterization of NGFFYamide neuropeptide from Patiria pectinifera pyloric caeca extract

Neuropeptides are small molecules that mediate intercellular signaling and regulate physiological processes. Starfish possess various myoactive neuropeptides, including starfish myorelaxant peptide (SMP) and a calcitonin-type peptide with apical muscle relaxing properties. In this study, we report the purification of a neuropeptide from starfish (Patiria pectinifera) pyloric caeca extract using high-performance liquid chromatography (HPLC) and an in vitro bioassay to screen for fractions and peptides with relaxing effects on P. pectinifera apical muscle preparations. A series of HPLC steps using reversed-phase and cation-exchange columns yielded a purified peptide with muscle-relaxing effects. The purified peptide's structure was determined by LC-MS and Edman degradation, revealing a pentapeptide with an amidated C-terminus (NGFFYamide) and a molecular mass of 646.2930 Da. This is the first report of NGFFYamide purification from P. pectinifera through biochemical methods. The nucleotide sequence encoding the NGFFYamide precursor was determined, showing the presence of a conserved neurophysin domain in the C-terminal region. RT-qPCR results confirmed high expression in radial nerves cord, consistent with previous findings on NG peptides in echinoderms. In vitro pharmacological studies on muscle preparations from P. pectinifera and Asterias amurensis revealed differential relaxing activity of NGFFYamide on apical muscles, while its effects on tube foot preparations were similar in both species. NGFFYamide also induced potent contraction in P. pectinifera cardiac stomach. Comparison of three NG peptides (NGFFYamide, NGFFFamide, and NGIWYamide) on P. pectinifera cardiac stomach revealed varying potency, suggesting class-specific receptor interactions. Tachyphylaxis was observed in P. pectinifera apical muscle but not in A. amurensis, warranting further investigation. Based on these results, it is plausible that NGFFYamide could be involved in regulating locomotion and feeding behavior in P. pectinifera, consistent with findings in Asterias rubens.

Botulinum Toxin Enhanced Foker Process for Long Gap Esophageal Atresia

BackgroundThe traction-induced esophageal growth (Foker) process for the treatment of long gap esophageal atresia (LGEA) relies on applying progressive tension to the esophagus to induce growth. Due to its anti-fibrotic and muscle-relaxing properties, we hypothesize that Botulinum Toxin A (BTX) can enhance traction-induced esophageal growth. MethodsA retrospective two-center cohort study was conducted on children who underwent a BTX-enhanced Foker process for LGEA repair from 2021 to 2023. BTX (10 units/ml, 2 units/kg, per esophageal pouch) was applied at the time of traction initiation. Time on traction, complications, and anastomotic outcomes were compared against historical controls (Foker process without BTX) from 2014 to 2021. ResultsTwenty infants (LGEA type A:12, B:4, C:4; 35% reoperative; median [IQR] age 3 [2–5] months), underwent BTX-enhanced Foker process (thoracotomy with external traction: 9; minimally invasive [MIS] multi-staged internal traction: 11). Mean gap lengths were similar between BTX-enhanced external and external traction control patients (mean [SD], 50.6 mm [12.6] vs. 44.5 mm [11.9], p = 0.21). When compared to controls, the BTX-enhanced external traction process was significantly faster (mean [SD], 12.1 [1.6] days vs. 16.6 [13.2] without BTX, p = 0.04) despite similar preoperative gap lengths. There was no difference in time on traction for those undergoing a minimally invasive process. There were no significant differences in complications or anastomotic outcomes in either cohort. ConclusionBotulinum toxin may play a role in accelerating the traction-induced esophageal growth process for LGEA repair. Minimizing time on traction can decrease sedation and paralysis burden while on external traction. Further studies are needed to elucidate the effects of BTX on the esophagus. Level of EvidenceLevel III. Type of StudyRetrospective, Two-center, Cohort study.

The Impact Of Lavender Aromatherapy Techniques And Endorphin Massage On Anxiety During The First Active Phase

Stress and an overabundance of catecholamine hormones released during labor can cause smooth muscle and uterine ischemia, which heightens pain impulses. A light touch or therapeutic massage stimulating the body to release endorphin compounds can relieve pain and comfort. This type of massage is known as endorphin massage. Linalool, a compound found in lavender aromatherapy, has calming and muscle-relaxing properties. This research project aims to ascertain "The Effectiveness of Lavender Aromatherapy and Endorphin Massage on Anxiety of Labor Pain in the First Active Phase in the Working Area UPTD Puskesmas Sukahaji." This study used a quasi-experimental design with pre-and post-test methods and a control group design carried out in the working area of UPTD Puskesmas Sukahaji. Purposive sampling was used to obtain samples. Purposive sampling was used to collect samples from 120 individuals. The Wilcoxon and Kruskal Wallis tests were used in the data analysis. The Wilcoxon test in bivariate analysis produced a p-value of less than 0.005 for every intervention group. The endorphin massage group's mean rank for the anxiety variable was 57.08; the control group's was 45.17; the lavender aromatherapy group's was 72.53; and the combination group's was 67.22. In conclusion, the anxiety associated with labor pain was impacted by endorphin massage, lavender aromatherapy, and the combination of the two. The best treatment for lowering anxiety was lavender aromatherapy, and the best way to lessen the severity of labor pain was to combine lavender aromatherapy with endorphin massage. Recommendation: It is believed that aromatherapy with lavender and endorphin massage can be used as alternative ways to reduce anxiety and the intensity of labor pain.

Effect of nifedipine administration before embryo transfer on reproductive outcome in ICSI cycles, a double-blind control trial study.

Nifedipine is a calcium channel blocker with smooth muscle relaxing properties. This study set out to investigate the efficacy of nifedipine administered orally before embryo transfer (ET) on the improvement of theintracytoplasmic sperm injection (ICSI) outcome. This randomized, double-blind, comparator-controlled, was carried out between 2019 and 2020 in the infertility center of Babol, Iran. 200 women candidates for ICSI and recipients of frozen-thawed ET aged 18-40years were randomly assigned in the ratio 1:1 to an intervention group that received nifedipine 20mg tablets orally 30min before ET (n = 100) or to a group of placebo (n = 100). A randomization center in Babol University of Medical Science used computer-generated numbers to allocate treatments. The allocation treatment was blind to the participants, the sonographer of endometer monitoring, the staff of the ICSI laboratory, and the outcome assessor. The primary analysis was based on the intention-to-treat principle done on 200 participants, (n = 100), comparing chemical pregnancy rates in the two comparing groups at 14days' follow-up after ET. Implantation rate and clinical pregnancy were considered secondary outcomes. 200 participants were analyzed. There is no significant difference in the number of oocytes and the quality of embryos in the nifedipine and placebo groups. Despite a numerical increase in the rate of chemical pregnancy, there were no statistical differences in the study group versus the comparison group (24% vs 14%, P = 0.1, rate ratio 0.88, 95% CI 0.77 to 1.01), respectively. Also, no significant increase in clinical pregnancy was found compared with the placebo (17% vs 8%, P = 0.26, rate ratio 0.90, 0.81 to 1.00). Nifedipine administered orally 30min before embryo transfer did not improve the chemical pregnancy rate, and clinical pregnancy rate in infertile women undergoing ICSI. This trial has been registered on the Iranian Clinical Trials Registration Site (IRCT) with the number IRCT20180417039338N3.

Skeletal muscle fiber type and TMS-induced muscle relaxation in unfatigued and fatigued knee-extensor muscles.

The force drop after transcranial magnetic stimulation (TMS) delivered to the motor cortex during voluntary muscle contractions could inform about muscle relaxation properties. Because of the physiological relation between skeletal muscle fiber-type distribution and size and muscle relaxation, TMS could be a noninvasive index of muscle relaxation in humans. By combining a noninvasive technique to record muscle relaxation in vivo (TMS) with the gold standard technique for muscle tissue sampling (muscle biopsy), we investigated the relation between TMS-induced muscle relaxation in unfatigued and fatigued states, and muscle fiber-type distribution and size. Sixteen participants (7F/9M) volunteered to participate. Maximal knee-extensor voluntary isometric contractions were performed with TMS before and after a 2-min sustained maximal voluntary isometric contraction. Vastus lateralis muscle tissue was obtained separately from the participants' dominant limb. Fiber type I distribution and relative cross-sectional area of fiber type I correlated with TMS-induced muscle relaxation at baseline (r = 0.67, adjusted P = 0.01; r = 0.74, adjusted P = 0.004, respectively) and normalized TMS-induced muscle relaxation as a percentage of baseline (r = 0.50, adjusted P = 0.049; r = 0.56, adjusted P = 0.031, respectively). The variance in the normalized peak relaxation rate at baseline (59.8%, P < 0.001) and in the fatigue resistance (23.0%, P = 0.035) were explained by the relative cross-sectional area of fiber type I to total fiber area. Fiber type I proportional area influences TMS-induced muscle relaxation, suggesting TMS as an alternative method to noninvasively inform about skeletal muscle relaxation properties.NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS)-induced muscle relaxation reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. We showed that fiber type I proportional area influences the TMS-induced muscle relaxation, suggesting that TMS could be used for the noninvasive estimation of muscle relaxation in unfatigued and fatigued human muscles when the feasibility of more direct method to study relaxation properties (i.e., muscle biopsy) is restricted.

Antifungal and Antiproliferative Activity of Pistagremic Acid and Flavonoids Extracted from the Galls of Pistacia chinensis subsp. integerrima.

Pistacia chinensis subsp. integerrima (J.L. Stewart) Rech. f. is a plant known for its therapeutic applications in traditional medicine, which are related to its antimicrobial, anticancer, antioxidant, anti-inflammatory, analgesic, antidiarrheal, and muscle relaxant properties. The galls of P. chinensis are rich in triterpenes and flavonoids, and we here report the extraction of pistagremic acid (1), apigenin (2) and sakuranetin (3) from this source. The isolated compounds were tested against Aspergillus flavus, Candida albicans, Candida glabrata, Fusarium solani, Microsporum canis and Trichoderma longibrachiatum. The results highlighted the antimicrobial activity of flavonoids 2 and 3, suggesting that this class of molecules may be responsible for the effect related to the traditional use. On the other hand, when the compounds and the extract were tested for their antiproliferative activity on a panel of 4 human cancer cell lines, the triterpene pistagremic acid (1) showed a higher potential, thus demonstrating a different bioactivity profile. Structure-based docking and molecular dynamics simulations were used to help the interpretation of experimental results. Taken together, the here reported findings pave the way for the rationalization of the use of P. chinensis extracts, highlighting the contributions of the different components of galls to the observed bioactivity.

Evaluation of skeletal muscle relaxant activity of hydroalcoholic extract of Curcuma amada rhizome in Wistar rats

Background: Curcuma amada rhizome is an indigenously used medicine to treat all kinds of prurigo, bronchitis, asthma, biliousness, diarrhea, hiccough, inflammations due to injuries, and lumbago. Aims and Objectives: The objectives of the study are to assess the skeletal muscle relaxant activity of hydroalcoholic extract of C. amada rhizome in Wistar rats. Materials and Methods: Extract was prepared according to the method of Rosenthaler using Soxhlet apparatus. Toxicity studies from previous literature had already proved the safety of the drug. The research was carried out following approval from the Institutional Animal Ethics Committee. The Wistar rats were orally administered with doses of 200, 400, and 800 mg/kg of the extract. The muscle relaxant action was assessed by rotarod method. Data analysis involved the use of paired t-test and one-way analysis of variance (ANOVA) through the Statistical Package for the Social Sciences software version 16. Results: The fall off time was significantly reduced when administering extracts with doses of 200, 400, and 800 mg/kg (paired t-test, P &lt; 0.001) compared to the control group, which consisted of the same animals before the administration of the test drug. The results when evaluated using ANOVA showed F = 16.203, P &lt; 0.001. Dunnett’s test was utilized for post hoc analysis, revealing a notable change in muscle relaxation induced by the 200 mg/kg and 800 mg/kg doses of extract. Conclusion: Findings of our study substantiate the use of C. amada rhizome for its skeletal muscle relaxant property in the treatment of various inflammatory conditions.

Flavones isolated from Pseudognaphalium liebmannii with tracheal smooth muscle relaxant properties

The inflorescences of Pseudognaphalium liebmannii are used as folk medicine to treat various respiratory diseases. In this work, we report the isolation of seven known flavones: 5-hydroxy-3,7-dimethoxyflavone 1, 5,8-dihydroxy-3,7-dimethoxyflavone 2, 5,7-dihydroxy-3,8-dimethoxyflavone 3 (gnaphaliin A), 3,5-dihydroxy-7,8-dimethoxyflavone 4 (gnaphaliin B), 3,5-dihydroxy-6,7,8-trimethoxyflavone 5, 3,5,7-trimethoxyflavone 6 and 3-O-methylquercetin 7. All these flavones except 1 and 6 showed a relaxant effect on guinea pig tracheal preparation with EC50 between 69.91 ± 15.32 and 118.72 ± 7.06 µM. Aminophylline (EC50 = 122.03 ± 7.05 µM) was used as a relaxant reference drug. The active flavones shifted the concentration-response curves of forskolin and nitroprusside leftward, and significantly reduced the EC50 values of these drugs. Furthermore, these flavones dose-dependently inhibited phosphodiesterase (PDE) in an in vitro assay. This reveals that the inflorescences of P. liebmannii contain several flavones with relaxant effect on airway smooth muscle and with PDEs inhibition that contribute to supporting the anti-asthmatic traditional use.

The influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents

Anxiety disorders represent one of the most prevalent categories of psychiatric illnesses, affecting individuals regardless of gender, age, or social standing. They result in substantial personal and societal costs. The pursuit of novel pharmacological approaches for treating these disorders is driven by the increasing medical necessity to enhance the effectiveness and safety profiles of anxiolytic medications. Due to the fact that benzodiazepines and their derivatives have anti-anxiety, hypnotic-sedative, antidepressant, anticonvulsant, and muscle relaxant properties, they occupy a leading place in the treatment of anxiety disorders. An essential aspect of investigating the pharmacological activity of new triazolobenziazepine derivatives is assessing their impact on rodent muscle tone and coordination of movements. The aim of the work is to find out the influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents in the “vertical grid” test and coordination of movements using the rotarod test. Materials and methods. The objects of the study were 5 new derivatives of 1,2,3-triazolo-1,4-benzodiazepines. Before conducting in vivo experiments, these derivatives were mixed with lactose at a ratio of 1:1000. The “vertical grid” test and rotarod test (rotating rod test) were used to reproduce the model of motor behavior of rodents. Results. The presence of a tendency to the manifestation of a myorelaxant effect in the “vertical grid” test was established. The indicator of the total duration of detention at the facilities was similar and did not differ significantly in the control and experimental groups at doses of 0.50 mg/kg and 0.75 mg/kg. Derivatives MA-252, MA-253 and MA-254 at a dose of 1 mg/kg reduced the total duration of retention on the vertical grid, which indicates their mild muscle relaxant effect. In the rotating rod test, MA-253 derivative at a dose of 1 mg/kg increased the retention time on the rotarod, which demonstrates greater physical endurance of the animals of these experimental groups. Conclusions. The study’s findings indicated that the 1,2,3-triazolo-1,4-benzodiazepine derivatives did not exhibit an adverse impact on movement coordination. Some of these derivatives demonstrated a mild muscle relaxant effect. These results support the need for further research into their influence on spontaneous motor activity. Additionally, there’s a necessity to determine the dosage regimen, establish an effective dose, and adapt it for human use.

Exploring the therapeutic potential of fisetin: a comprehensive study on its anti-nociceptive and anti-inflammatory effects.

This study's primary objective was to explore and validate the pain-relieving and inflammation-reducing properties of fisetin, a flavonoid known for its antioxidant benefits, using different mouse models. We assessed fisetin's pain-relieving effects using mouse models exposed to both heat-induced and chemical-induced pain. The inflammation-reducing capacity of fisetin was evaluated using the carrageenan-triggered paw swelling test, focusing on the influx of leukocytes in the peritoneal space. The air pouch test was utilized to determine fisetin's ability to counteract proinflammatory cytokines. The performance of fisetin, when paired with opioid blockers, was analyzed, and juxtaposed with results from conventional medicines. The muscle-relaxing potential of fisetin was assessed through the open field assessment. Fisetin consistently demonstrated marked anti-inflammatory actions across various models. It also proved to be effective in reducing pain in the pain-induced models. When combined with opioid blockers, fisetin's effects were on par with those of traditional medications. Noteworthily, fisetin displayed muscle-relaxing properties in the open-field assessment. The compiled data showcases fisetin as a powerful anti-inflammatory agent with significant pain-relieving capacities, positioning it as a promising contender for pain treatment modalities.

Non-pharmaceutical management of chronic pain

Chronic pain is a complex and pervasive condition that challenges both individuals and healthcare systems. In light of concerns about overreliance on pharmacological interventions, non-pharmacological approaches have gained prominence in chronic pain management. This article explores the scientific basis and benefits of diverse non-pharmacological interventions, including physical exercise, manual therapies, cognitive-behavioral therapy (CBT), meditation, acupuncture, and herbal medicine, in alleviating chronic pain. Each intervention's mechanisms of action are elucidated, shedding light on their physiological and psychological effects. Physical exercise has emerged as a cornerstone of non-pharmacological pain management, offering benefits such as pain reduction, enhanced mobility, and improved quality of life. Mechanisms encompass endorphin release, anti-inflammatory effects, and central nervous system modulation. Manual therapies, represented by chiropractic manipulation, osteopathic manipulative treatment , and massage therapy, demonstrate significant pain relief through mechanisms involving joint mobilization, muscle relaxation, and neurophysiological responses. Cognitive-behavioral therapy (CBT) operates through cognitive restructuring, behavioral modification, and pain perception modulation. Meditation practices, such as mindfulness and meditation-based pain relief, cultivate mindfulness and promote emotional regulation, leading to reduced pain perception and improved overall well-being. Acupuncture, a traditional Chinese therapy, involves needling specific points to achieve pain relief through mechanisms like endorphin release, neural pathway modulation, and anti-inflammatory effects. Herbal medicine, with its rich pharmacopeia, contributes to pain management through anti-inflammatory, analgesic, and muscle relaxant properties. Mechanisms encompass modulation of neurotransmitters, prostaglandins, and ion channels. Collectively, these non-pharmacological interventions empower individuals to actively engage in their pain management and improve their quality of life.

Tylophora indica (Burm. f.) Merr alleviates tracheal smooth muscle hyperresponsiveness in ovalbumin-induced allergic-asthma model in guinea-pigs: Evidences from ex vivo, in silico and in vivo studies.

Tylophora indica (Burm. f.) Merr is a climbing perennial plant reported in Indian traditional system of medicine for its use in allergy and asthma. However, only few scientific studies have been performed in the past to validate its antiasthmatic potential. The present study deals with investigation of airway smooth muscle relaxant and antiasthmatic potential of extract and subsequent fractions prepared from T.indica. The most active fraction of T.indica leaves selected through bio-guided activity was subjected to liquid chromatography-mass spectrometry (LC-MS) analysis for chemical profiling. The binding affinity of identified compounds in fraction towards M3 and H1 receptors was determined by molecular docking study. F-2 (chloroform fraction prepared from methanolic extract of T.indica leaves) was examined for its smooth muscle relaxant properties using isolated trachea of guinea-pig. Further, F-2 was evaluated through in vivo studies employing ovalbumin-induced asthma model in guinea-pigs. F-2 was found most effective in bioassay-guided fractionation. Characterization by LC-MS analysis revealed presence of five major bioactive compounds in F-2 that showed good docking interactions with M3 and H1 receptors. The ex vivo study demonstrated that F-2 could significantly relax tracheal rings via targeting multiple signalling pathways videlicet, namely, noncompetitive antagonism of the histamine and muscarinic receptors, β2-adrenergic stimulation and activation of soluble guanylyl cyclase. In in vivo studies, F-2 ameliorated airway hyperresponsiveness and decreased broncho alveolar lavage fluid (BALF) levels of inflammatory cytokines and immunoglobulin E (IgE). These results confirm the traditional use of T.indica as an antiasthmatic agent which are evidenced through ex vivo, in silico and in vivo studies.

Benzodiazepines: Kamo griadeshi?

BENZODIAZEPINES: KAMO GRIADESHI? Mykolay Ya. Golovenko A. V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Lyustdorfs’ka doroha Str., 86, Odesa 65080, Ukraine Introduction. Benzodiazepines are among the most prescribed medications in the world because of their demonstrated effectiveness at treating serious physical and mental disorders. The high frequency of clinical use is because of their anxiolytic, anticonvulsant, amnestic, muscle relaxant, and sedative-hypnotic properties. Unfortunately, benzodiazepines also cause unwanted side effects, for example excessive (or unwanted) sedation, tolerance, dependence, and a abuse. The aim – by combining own pharmacological and medical studies together with the systematized literature data to determine the historical circumstances, which facilitated BDZs to lead the all the lists of "the most frequently prescribed" following by oblivion. To set up the future way marks for these compounds. Quo vadis, BDZs? And toward what our path lies? To foresee the possible obstacles and challenges on the thorny way of use of well-known and creating of innovative BDZs derivatives. Materials and methods. When writing the review, searches were undertaken in two representative databases: PubMed and Google Scholar. The search of scientific articles published from 1970 to 2022 was performed. Results and conclusions. The available publication data were systemized and the brief information concerning the BDZs derivatives administration was provided. It was found that in most of the cases throughout the long period, BDZs perceiving still remains negatively biased without substantial scientific background. More and more often the appeals rise to renew the deliberations of problems of the medical use of BDZs in adherence to the exact prescriptions and conceptual stringency in the related comments. The social aspects of benzodiazepines administrations were discussed. The common conclusion was made that benzodiazepines use in the ranges of corresponding medical practice significantly overbalances the possible problems. Considered the possibilities of creating selective innovative medicines as new BDZs derivatives and the conveniences of their use. Keywords: benzodiazepines, indications, side effects, «designer benzodiazepine», improving access.

In silico pharmacology and bioavailability of bioactive constituents from Triclisia subcordata (Oliv), an underutilized medicinal plant in Nigeria

Medicinal plants are rich sources of traditional medicines from which many modern medicines are made. Triclisia subcordata Oliv. is one among the underutilized medicinal plants in the Southwestern part of Nigeria. Therefore, this study was designed to present comprehensive data from the literature on pharmacological uses of T. subcordata and its phytochemistry, and to predict the pharmacology and bioavailability of the phytoconstituents isolated so far from Triclisia subcordata through an in silico approach. T. subcordata has high antioxidant activity and so it isthus used to treat oxidative stress-related diseases such as inflammation and diabetes. It also has antibacterial, antifungal, antimalarial and smooth muscle relaxing properties. It is a potent inhibitor of enzymes such as alpha-amylase and alpha-glucosidase. It has also traditionally been used in cancer treatment. One of the bisbenzylisoquinoline (BBIQ) alkaloids isolated from this plant, cycleanine, showed selectivity for ovarian cancer cell lines. The presence of phytochemicals such as cyanogenic glycosides and tannins in low concentrations in T. subcordata has also been reported to make it edible to humans. The results of predicted absorption, distribution, metabolism, excretion and toxicity was analyzed on the webserver ’ADEMTLab 2.0‘ . Prediction of activity studies for the four bisbenzylisoquinoline alkaloids isolated so far from this plant supported anticancer, antimicrobial, antidiabetic, antiulcer, antimalarial activities as well as muscle relaxant effect. Moreover, new activities including stimulation of leukopoiesis, inhibition of membrane permeability , inhibition of kinase and nicotinic alpha4beta4 receptor agonist properties were also predicted through in silico investigation. From our findings, these phytoconstituents could be lead candidates in drug discovery, since this plant is safe for human consumption.

Detection and isolation of intestinal muscle relaxant substances from the root of Taverniera abyssinica A. Rich

Ethnopharmacological relevanceIn Ethiopian traditional medicine the root of Taverniera abyssinica A.Rich is known as a remedy for sudden gastrointestinal cramping and fever. In this study we have isolated and identified the bioactive principle of Taverniera abyssinica that exerts effects on isolated smooth muscle tissues of the rabbit duodenum and guinea-pig ileum. Aim of the studyTo isolate and purify the bioactive principle from the root of Taverniera abyssinica A.Rich by bioassay-guided fractionation, HPLC purification and masspectrometry, with further investigation of its bioactivity on isolated smooth muscle strips. Materials and methodsRoots of Taverniera abyssinica A.Rich extracted in 75% methanol/water were fractioned with a reverse phase column and then subjected to HPLC purification. Each fraction collected from the HPLC was tested for its bioactivity using electric field stimulation-evoked contractions of the rabbit duodenum and guinea-pig ileum. Finally, detailed structural analysis of the fraction displaying significant bioactivity was made by mass spectrometry. ResultsThrough bioassay-guided fractionation and HPLC purification the bioactive fractions were identified. These were tested for bioactivity on isolated smooth muscle strips which showed about 80% inhibition of contractions evoked by electric field stimulation. These compounds were identified as formononetin, afrormosin and tectorigenin by using masspectrometry applying relevant standards for detection. ConclusionThe traditionally claimed smooth muscle-relaxing effect of the roots of Taverniera abyssinica A.Rich is essentially due the three isolated and purified the two isoflavones formononetin, afrormosin as well as the metoxyisoflavone tectorigenin, along with possibly other not yet purified bioactive substances, however with similar smooth muscle-relaxing properties.

Proton Pump Dysfunction and Upregulation of Caspase-3 Activity via Oxidative-Sensitive Signaling Mediate Rohypnol-Induced Testicular Toxicity

Rohypnol is a benzodiazepine that is used for its anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties, but commonly abused. It has been reported to induce sexual dysfunction; however, its effect on testicular integrity and sperm quality is yet to be documented. This study evaluated the impact of Rohypnol on testicular integrity, circulatory testosterone, spermatogenesis, and sperm quality. The likely role of oxidative stress-dependent pathway as well as testicular proton pumps and caspase-3 activity in Rohypnol-induced modulation of male reproductive function was explored. In this study, adult male rats were randomized into six groups of six rats each: the control received 1 ml of distilled water as vehicle, while the low- and high-dose Rohypnol-treated groups received 2 mg/kg and 4 mg/kg of Rohypnol for four weeks. The control-, low-, and high-dose recovery groups received 2 mg/kg and 4 mg/kg of Rohypnol for four weeks, respectively, which was followed by a 4-week drug-free recovery period. Rohypnol treatments led to impaired steroidogenesis and spermatogenesis and low sperm quality. This was accompanied by a rise in the markers of testicular injury, oxidative stress, inflammation, and apoptosis. Also, the activities of testicular enzymatic antioxidants and proton pumps were significantly reduced. Although the impacts of low-dose Rohypnol treatment were partially reversible, those of the high-dose Rohypnol treatment were not. Histopathological findings on the testicular tissues were in tandem with the biochemical alterations. Thus, it is safe to infer that Rohypnol induces testicular damage by the suppression of Na+/K+-ATPase and Ca2+-ATPase and the activation of caspase-3 through an oxidative-sensitive signaling pathway.

Bioactive Compounds from Kalanchoe Genus Potentially Useful for the Development of New Drugs.

The genus Kalanchoe Adans. (Crassulaceae) is native to Madagascar and comprises 145 species, being naturalized in the tropics and cultivated worldwide. In addition to having ornamental value, several Kalanchoe species are commonly used in popular medicine for the treatment of inflammatory conditions, wounds, gastric ulcers, and other diseases. The great importance of the genus is reflected on its acknowledgment by traditional and alternative health systems and organizations, as well as on the growing number of papers reporting pharmacological properties of extracts and isolated compounds from Kalanchoe. Among these properties, we highlight anti-inflammatory, antitumor, wound healing, antiulcer, and muscle relaxing properties. These activities are attributed mostly to flavonoids and bufadienolides, the main secondary metabolites reported in Kalanchoe extracts. While bufadienolides are generally related to cytotoxic and muscle relaxing activities, flavonoids are commonly reported as anti-inflammatory and wound healing agents. This review provides up to date information and perspectives on bioactive compounds from the Kalanchoe genus that are potentially useful for the development of new drugs. It includes not only a discussion on the advantages of the Kalanchoe species as source of bioactive compounds, but also the gaps, opportunities, and challenges to translate the acquired knowledge into innovation for drug development.