Auswahl der wissenschaftlichen Literatur zum Thema „Antispasmodic activity“

Natural products with antispasmodic activity have been used in traditional medicine to alleviate different illnesses since the remote past. We searched the literature and compiled the antispasmodic activity of 248 natural compounds isolated from terrestrial plants. In this review, we summarized all the natural products reported with antispasmodic activity until the end of 2017. We also provided chemical information about their extraction as well as the model used to test their activities. Results showed that members of the Lamiaceae and Asteraceae families had the highest number of isolated compounds with antispasmodic activity. Moreover, monoterpenoids, flavonoids, triterpenes, and alkaloids were the chemical groups with the highest number of antispasmodic compounds. Lastly, a structural comparison of natural versus synthetic compounds was discussed.

Tagetes lucida has been used in traditional medicine as a remedy to alleviate several gastrointestinal disorders that provoke stomachaches, abdominal cramps, and diarrhea. However, there is not enough scientific evidence that supports these effects. Therefore, the purpose of this study was to evaluate antispasmodic and antidiarrheal activities of aqueous extract of T. lucida (AqExt-TL) as well as its mechanism of action in experimental models. Antispasmodic activity and the mechanism of action of AqExt-TL were assessed on segments of the guinea pig ileum precontracted with KCl, acetylcholine (ACh), or electrical field stimulation (EFS). Furthermore, the antispasmodic effect of two coumarins (umbelliferone and herniarin) previously identified in this species was evaluated. Antidiarrheal activity of AqExt-TL was determined using the charcoal meal test in mice. AqExt-TL showed antispasmodic activity in segments of the guinea pig ileum precontracted with KCl (83.7 ± 1.9%) and ACh (77.2 ± 5.3%) at the maximal concentration; however, practically, it did not alter the contractions induced by EFS (10.1 ± 2.2%). Antispasmodic activity of AqExt-TL was not significantly altered by hexamethonium (a ganglionic blocker) or L-NAME (an inhibitor of nitric oxide synthase). However, this extract decreased the maximal contractile response to calcium (82.7 ± 8.5%), serotonin (68.1 ± 8.5%), and histamine (63.9 ± 5.9%) in their concentration-response curves. Umbelliferone and herniarin also induced an antispasmodic effect on tissues precontracted with KCl. In addition, low doses of AqExt-TL reduced to 50% the distance traveled by charcoal meal in the gastrointestinal transit model in mice as loperamide, an antidiarrheal agent, did. These results provided evidence of the antispasmodic and antidiarrheal activity of T. lucida, which supports its use in the folk medicine in relieving symptoms in some gastrointestinal disorders. In the antispasmodic effect, the blockade of histaminergic and serotoninergic pathway as well as the calcium channels seems to be involved. Finally, umbelliferone and herniarin could be partially responsible for the antispasmodic activity induced by T. lucida.

Introduction. IBS is a functional bowel disorder that has a significant impact on patients and society, especially in terms of quality of life and medical costs.Pathogenesis. It is believed that the pathogenesis of IBS consists of several mechanisms: the syndrome of intersection of functional disorders (gut-brain), stress, visceral hypersensitivity and changes in motor skills.Visceral hypersensitivity. Changes in visceral sensitivity in IBS are characterized by central abnormalities in areas of the cerebral cortex. Motility impairment in IBS manifests itself as abnormal myoelectric activity in the colon, resulting in repetitive contractions of the small intestine and colon, which appear to cause pain.Intestinal microflora. FODMAPs are found in high amounts in some fruits, artificial sweeteners, legumes, and green vegetables and are poorly absorbed by all people. FODMAPs have enzymatic and osmotic effects that may contribute to the onset of symptoms in some patients.The principles of IBS therapy. Treatment for IBS should be based on the type and severity of symptoms. For the treatment of IBS, drugs of various pharmacological groups are used, depending on the prevailing symptoms. These include opioid receptor agonists, bile acid sequestrants, guanylate cyclase agonists, chlorine channel activators, as well as antibiotics, probiotics, antidepressants, 5-HT3 receptor antagonists, and antispasmodics.Myotropic antispasmodics. Drugs with antispasmodic activity are used to treat functional and organic diseases of the gastrointestinal tract as a basic therapy or «on demand». Mebeverine quickly and effectively relieves spasm, pain and the entire complex of intestinal symptoms, in addition, the drug reduces visceral hypersensitivity due to a local anesthetic effect. The drug has a high safety profile and has a number of advantages over drugs of the same pharmacological group.Conclusion. Myotropic antispasmodics have been shown to be highly effective in the treatment of IBS. Mebeverine occupies a special place among myotropic antispasmodics. Its combined action provides a pronounced antispasmodic activity along with a high safety profile.

The objective is to compare the effectiveness of complex bio-regulatory medication (CBRM) Viburcol, produced by «Biologishe Haylmittel Heel GmbH», Germany, with the reference product No-X-sha, produced by «Lekhim-Kharkov», which are used as antispasmodics, for preparation of uterine cervix for childbirth and prevention of labor anomalies. Patients and methods. 92 pregnant women aged 18 to 45 years, who were randomized into 2 groups: the main group (n=46) and the control (n=46) one, were involved in the study. Viburcol was used for the treatment of pathological preliminary period and prevention of development of labor anomalies. It was prescribed at the end of pregnancy and in the 1st stage of labor, in the morning and in the evening. Two Viburcol suppository every 3-4 hours were given at the onset of labor. Antispasmodic No-X-sha was used in the control group. It was studied the functional state of the sympathetic-adrenal system with fluorometric method, the concentration of noradrenaline (NA) and adrenaline (A) in the urine, to assess the neurohormonal regulation of labor. The plasma levels of b-estradiol and progesterone were determined to identify the risk of discoordination of labor activity and the state of uterine contractile function. Also, the parameters of uterine contractile activity were analyzed according to cardiotocography. Results. Usage of complex bio-regulatory medication Viburcol promotes adequate cervical ripening and incidence of discoordination of labor activity decreased by 1.5 times. CDRM Viburcol administration in childbirth facilitated the elimination of pathological levels of catecholamines, which led to the development of discoordination of labor activity. Conclusion. The results show the effectiveness of CDRM Viburcol (rectal suppositories) for the prevention of discoordination of labor activity. The medicine meets all modern requirements for antispasmodics and analgesics used during labor: it has analgesic, antispasmodic, anxiolytic effect, eliminates side reflex reactions, reduces the severity of birth stress, it has no adverse effect on the contractile activity of uterus and the fetus condition. Key words: complex bio-regulatory medications, bio-regulatory approach, labor amoralities, preparation of uterine cervix, Viburcol.

Black mulberry is a widely acknowledged ancient traditional medicine. Its extract and constituents have been reported to exert various bioactivities including antimicrobial, hypotensive, analgesic etc. effects. While black mulberry preparations are also used as antispasmodic agents in folk medicine, no related studies are available on its isolated constituents. Through an extensive chromatographic purification, seven phenolic compounds were isolated from the methanol extract of Morus nigra root bark, including morusin (1), kuwanon U (2), kuwanon E (3), moracin P (4), moracin O (5), albanol A (6), and albanol B (7). A complete NMR signal assignment of moracin P and O was achieved, and related literature errors confusing the identity of moracin derivatives are hereby clarified. Compounds 2, 5 and 7 were identified as strong antispasmodic agents on isolated rat ileum and tracheal smooth muscles, while compound 3, a methoxy derivative of 2, was inactive. Moracin O (5) inhibited the ileal and tracheal smooth muscle contractions with Emax values of 85% and 302 mg, respectively. Those actions were superior as compared with papaverine. Our findings demonstrate that prenylated arylbenzofurans, geranylated flavonoids and Diels-Alder adducts from Morus nigra are valuable antispasmodic agents. Compounds 2, 5 and 7 are suggested as marker compounds for quality control of antispasmodic mulberry preparations. Moracin O (5) is a new lead compound for related drug development initiatives.

Synthesis, antispasmodic and antidiarrheal activities of some 1-substituted imidazole derivatives A series of 1-substituted imidazoles 1a-d and 2a-d were synthesized and screened for antispasmodic and antidiarrheal activities. Antispasmodic activity was tested at various concentrations on isolated tissue preparations; concentration-response curves were plotted and compared with atropine. All compounds were found to inhibit contraction of the guinea pig ileum. Castor oil-induced diarrhea model in rats was used for evaluation of antidiarrheal activity. Parameters such as intestinal transit and volume of intestinal fluid were measured for antidiarrheal activity at 40 mg kg-1 dose and compared with the standard drug loperamide at 6 mg kg-1 dose. Defecation frequency in the test group was found to be significantly lower (p < 0.01) compared to the control group and comparable with that of the standard. The present study reveals that the compounds exert antidiarrheal activity through possible inhibition of intestinal movement and reduction of capillary permeability in the abdominal cavity.

Le Brésil est un pays qui présente une vaste biodiversité, en particulier dans la région de la Caatinga, dans le Nordeste. Dans ce biome poussent des plantes de la famille des Cordiaceae, qui sont utilisées par les communautés locales pour le traitement de certaines maladies. C’est notamment le cas des espèces Varronia dardani et V.leucocephala, dont les infusions sont utilisées pour soulager les douleurs gastriques, les coliques menstruelles et l'arthrite. L'objectif de ce travail était de contribuer à la connaissance de ces espèces, en étudiant leurs propriétés phytochimiques et biologiques. Le matériel végétal a été collecté à Serra Branca-PB et Maturéia-PB et soumis à des processus d'extraction. L'extrait éthanolique brut de V. dardani (EEB-VD) a été soumis à la détermination des composés phénoliques totaux et à la quantification de l'acide rosmarinique, considéré comme l'un des marqueurs chimio taxonomiques de la famille des Cordiaceae. Un criblage a été effectué avec le EEB-VD pour évaluer son activité spasmolytique dans différents organes. L'activité antiproliférative des extraits et fractions de ces espèces a également été évaluée contre des cellules de mélanome humain (A2058). En utilisant des techniques de RMN, les composés isolés des espèces étudiées ont été identifiés. Le screening concernant l'activité dans le muscle lisse, a montré que l’extrait EEB-VD présente une activité spasmolytique non sélective dans différents tissus et pour différents agonistes testés, avec une puissance maximale sur l’utérus des rats. À partir de la fraction acétate d'éthyle du EEB-VD, il a été possible d 'isoler et d'identifier cinq flavonoïdes, dont trois aglycones (isosakuranetine, naringenine et rhamnocitrine) et deux glycosylés (astragaline et isoquercitrine), en plus de l'acide rosmarinique. En ce qui concerne le test d’activité antiprolifératif sur cellules de mélanomes, la fraction isopropanolique de l'extrait de racines de V. dardani s'est révélée la plus active, et c'est à partir de cette fraction qu'a été isolé une nouvelle molécule, la vardanone, la première hydroanthraquinone rapportée dans l'espèce V.dardani. Ce composé a été évalué dans une étude chimio-informatique, dans laquelle l'activité de son groupe d'isomères sur la lignée cellulaire A2058 a été analysée, par rapport aux témoins positifs que sont la dacarbazine et le vemurafenib, des médicaments utilisés dans le schéma thérapeutique actuel du mélanome. La deuxième espèce la plus active dans les tests d’inhibition de prolifération était V. leucocephala, à partir de laquelle il a été possible d'isoler une saikosaponine, déjà isolée précédemment dans l'espèce. Ainsi, les résultats chimiques et biologiques, obtenus dans ce travail, ont contribué à la connaissance du genre Varronia, de plus, l'étude a révélé de nouvelles possibilités de recherche sur ces espèces grâce à la découverte de nouveaux métabolites secondaires, principalement de la classe des quinones
Brazil is a country that presents a vast biodiversity, where we find the Caatinga region, represented by plants of the Cordiaceae family, which are employed by local communities as an alternative for the treatment of some diseases, as is the case with the species Varronia dardani and V. leucocephala, whose infusions are used for the relief of gastric pain, menstrual colic, and arthritis. Therefore, the aim of this work was to contribute to the knowledge about these species, by studying their phytochemical and biological properties. To this end, the plant material was collected in the locations of Serra Branca-PB and Maturéia-PB and submitted to extraction processes. The crude ethanolic extract of V. dardani (CEE-VD) was submitted to the determination of total phenolics and to a quantification of rosmarinic acid, considered one of the chemotaxonomic markers of the Cordiaceae family. A screening was performed with CEE-VD to evaluate its spasmolytic activity in various organs. In addition to this biological activity, the antiproliferative activity of the extracts and fractions of all species was evaluated against human melanoma cells (A2058). Using NMR techniques, the compounds isolated from the study species were identified. The screening concerning the activity in smooth muscle, showed that CEE-VD showed a non-selectiv eactivity in the different tissues and for the different agonists tested, showing highest potency in the uterus of rats. From the ethyl acetate fraction of the CEE-VD it was possible the isolation and identification of five flavonoids, being three aglycones (isosakuranetin, naringenin, and rhamnocitrin) and two glycosylated (astragalin andisoquercitrin), besides rosmarinic acid. Regarding the cytotoxic test, the isopropanolicfraction of the extract of roots from V. dardani proved to be more active, and from this fraction the compound vardanone was isolated, the first hydro anthraquinone reported I nV. dardani species. This compound, was used for a chemo informatics study, where its set of isomers was analyzed for activity in the A2058 cell line and some interactions between amino acid residues were observed, compared to the positive controls dacarbazine and vemurafenib, drugs used in current melanoma therapy. The second most active species in the cytotoxic tests was V. leucocephala, from which it was possible to isolate a saikosaponin, already isolated previously in the species. Thus, the chemical and biological results, obtained in this work, contributed to the knowledge about the genus Varronia, furthermore, the study revealed new possibilities for research on these species involving the search for new secondary metabolites, mainly of the class of quinones
O Brasil é um país que possui uma vasta biodiversidade, onde encontramos a região da Caatinga, representada por vegetais da família Cordiaceae, os quais são empregados pelas comunidades locais como uma alternativa para o tratamento de algumas doenças,como é o caso das espécies Varronia dardani e V. leucocephala, cujas infusões são utilizadas para o alívio das dores gástricas, cólica menstrual e artrite. Sendo assim, buscou-se contribuir para o conhecimento sobre essas espécies, mediante o estudo fitoquímico e biológico das mesmas. Para isso, o material vegetal foi coletado nos municípios de Serra Branca-PB e Maturéia-PB e submetidos a processos de extração. O extrato etanólico bruto de V. dardani (EEB-VD) foi submetido à determinação defenólicos totais e à uma quantificação do ácido rosmarínico, considerado um dos marcadores quimiotaxonômicos da família Cordiaceae. Foi realizada uma triagem com o EEB-VD para avaliar a sua atividade espasmolítica em diversos órgãos. Além dessaatividade biológica, foi avaliada a atividade antiproliferativa dos extratos e frações de todas as espécies frente às células de melanoma humano (A2058). Através de técnicas de RMN foram identificadas as substâncias isoladas das espécies do estudo. A triagem relativa à atividade no músculo liso, mostrou que o EEB-VD apresentou uma atividade não seletiva nos diferentes tecidos e para os diferentes agonistas testados, apresentando maior potência no útero de ratos. Da fração acetato de etila do EEB-VD foi possível o isolamento e identificação de cinco flavonoides, sendo três agliconas (isosakuranetina, naringenina e ramnocitrina) e dois glicosilados (astragalina e isoquercitrina), além do ácido rosmarínico. Com relação ao teste citotóxico, a fração isopropanólica do extrato das raízes de V. dardani se mostrou mais ativa, e desta fração foi isolada a vardanona, primeira hidroantraquinona relatada na espécie V. dardani. O composto VD-R-I, foi utilizado para um estudo de quimioinformática, onde o conjunto de isômeros dessa substância foi analisado quanto à atividade na linhagem celular A2058 e foram observadas algumas interações entre resíduos de aminoácidos, comparando com ocontrole positivo dacarbazina e vemurafenibe, drogas utilizadas na terapia atual do melanoma. A segunda espécie mais ativa nos testes citotóxicos foi a V. leucocephala, de onde foi possível isolar uma saikosaponina, já isolada ateriormente na espécie. Logo, osresultados químicos e biológicos, obtidos nesse trabalho, contribuíram para o conhecimento sobre o gênero Varronia, ainda assim, o estudo revelou novas possibilidades de pesquisas nessas espécies envolvendo a busca de novos metabólitossecundários, principalmente da classe das quinonas

Terpenes are a class of chemical compounds with carbon and hydrogen atoms in their structure. They can be classified into several classes according to the quantity of isoprene units present in its structure. Terpenes can have their structure modified by the addition of various chemical radicals. When these molecules are modified by the addition of atoms other than carbon and hydrogen, they become terpenoids. Terpenes and terpenoids come from the secondary metabolism of several plants. They can be found in the leaves, fruits, stem, flowers, and roots. The concentration of terpenes and terpenoids in these organs can vary according to several factors such as the season, collection method, and time of the day. Several biological activities and physiological actions are attributed to terpenes and terpenoids. Studies in the literature demonstrate that these molecules have antioxidant, anticarcinogenic, anti-inflammatory, antinociceptive, antispasmodic, and antidiabetogenic activities. Additionally, repellent and gastroprotective activity is reported. Among the most prominent activities of monoterpenes and monoterpenoids are those on the cardiovascular system. Reports on literature reveal the potential effect of monoterpenes and monoterpenoids on systemic blood pressure. Studies show that these substances have a hypotensive and bradycardic effect. In addition, the inotropic activity, both positive and negative, of these compounds has been reported. Studies also have shown that some monoterpenes and monoterpenoids also have a vasorelaxing activity on several vascular beds. These effects are attributed, in many cases to the blocking of ion channels, such as voltage-gated calcium channels. It can also be observed that monoterpenes and monoterpenoids can have their effects modulated by the action of the vascular endothelium. In addition, it has been shown that the molecular structure and the presence of chemical groups influence the potency and efficacy of these compounds on vascular beds. Here, the effect of several monoterpenes and monoterpenoids on systemic blood pressure and vascular smooth muscle will be reported.