Antispasmodic Effect of Alstonia boonei De Wild. and Its Constituents: Ex Vivo and In Silico Approaches.

BACKGROUND: Alstonia boonei, belonging to the family Apocynaceae, is one of the best-known medicinal plants in Africa and Asia. Stem back preparations are traditionally used as muscle relaxants. This study investigated the antispasmodic properties of Alstonia boonei Stem back and its constituents. METHOD: The freeze-dried aqueous Stem back extract of A. boonei, as well as dichloromethane (DCM), ethyl acetate, and aqueous fractions, were evaluated for their antispasmodic effect via the ex vivo method. Two compounds were isolated from the DCM fraction using chromatographic techniques, and their antispasmodic activity was evaluated. An in silico study was conducted by evaluating the interaction of isolated compounds with human PPARgamma-LBD and human carbonic anhydrase isozyme. RESULTS: The Stem back crude extract, DCM, ethyl acetate, and aqueous fractions showed antispasmodic activity on high-potassium-induced (K+ 80 mM) contractions on isolated rat ileum with IC50 values of 0.03 ± 0.20, 0.02 ± 0.05, 0.03 ± 0.14, and 0.90 ± 0.06 mg/mL, respectively. The isolated compounds from the DCM fraction were ß-amyrin and boonein, with only boonein exhibiting antispasmodic activity on both high-potassium-induced (IC50 = 0.09 ± 0.01 µg/mL) and spontaneous (0.29 ± 0.05 µg/mL) contractions. However, ß-amyrin had a stronger interaction with the two proteins during the simulation. CONCLUSION: The isolated compounds boonein and ß-amyrin could serve as starting materials for the development of antispasmodic drugs.

Myorelaxant and antispasmodic effects of the essential oil of Artemisia campestris L., and the molecular docking of its major constituents with the muscarinic receptor and the L-type voltage-gated Ca2+channel.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrointestinal disorders are among the most common diseases that cause discomfort to people who are affected. In Morocco, aromatic and medicinal plants are widely used to calm these pains and eliminate their symptoms. Among these plants, Artemisia campestris L. which is used in eastern Morocco to treat digestive system problems. AIM OF THE STUDY: Our study aimed to experimentally verify the traditional use of this plant by evaluating the myorelaxant and antispasmodic effects of the essential oil of Artemisia campestris L. (EOAc). MATERIALS AND METHODS: Gas Chromatography-Mass Spectrometry analysis (GC-MS) was performed to identify the compounds present in the EOAc. Then, these molecules were subjected to the in silico study for molecular docking. The myorelaxant and antispasmodic evaluation of the EOAc were tested in vitro on an isolated rabbit and rat jejunum mounted on an organ bath. Then, an isotonic transducer connected to an amplifier recorded the graph related to intestinal contractility. RESULTS: GC-MS analysis of the essential oil of Artemisia campestris L. showed the presence of m-Cymene (17.308%), Spathulenol (16.785%), ß Pinene (15.623%), α Pinene (11.352%), α.-Campholenal (8.848%) as main constituents. The EOAc gave a dose-dependent and reversible myorelaxant effect on the spontaneous contractions of jejunum isolated from rabbits, with an IC50 equal to 72.16 ± 15.93 µg/mL. This effect did not occur through adrenergic receptors. The EOAc has an antispasmodic effect on the contractions of rat jejunal induced by a medium with low (25 mM) or high concentration (75 mM) of KCl, and carbachol 10-6 M. The obtained inhibitory effects are comparable to those of a non-competitive antagonist of cholinergic receptors. The major compounds of EOAc allowed the establishment of a relationship between these phytoconstituents and the antispasmodic effect found by the EOAc. The obtained results are also supported by a docking study. CONCLUSION: The obtained results confirm favorably the use of Artemisia campestris L. in traditional Moroccan medicine for the treatment of digestive tract illness, which gives us a new route to valorize the effects obtained by a phytomedicine specific for the digestive tract.

Antidiarrheal, antisecretory and intestinal smooth muscle relaxant effects of Platanus orientalis in mice.

Platanus orientalis is traditionally used to treat diarrhea and spasm. However, studies are lacking on its mechanism of action in diarrhea and spasm. Pharmacological in-vivo activities were performed. In-vitro activities were carried out to explore the underlying mechanism(s) of action in isolated tissue preparations of mice jejunum and ileum. Crude extract of Platanus orientalis, loperamide and verapamil were used. The crude extract provided dose-dependent protection in castor oil diarrhea like verapamil and reduced the intestinal fluid accumulation and charcoal meal transit distance. In-vitro studies produced spasmolytic effect on the spontaneous (EC50 value=0.21mg/mL), high K+ (EC50 value=0.37mg/mL) and carbachol (CCh)-induced contractions 5.35mg/mL (3.88-6.85) respectively. The quiescent ileum responded well to the high K+ and carbachol (CCh)-induced contractions when tested against crude extract. It caused inhibition of the induced contraction with EC50 values of 0.20mg/mL (0.10-0.30) and 3.25mg/mL (2-4.5) respectively and showed potent effect against CCh-induced contractions. Calcium response curves produced a similar effect to verapamil. The crude extract of Platanus orientalis remained safe up to 5g/kg dose.

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 RELEVANCE: Berberis 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 STUDY: To 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 METHODS: LC 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. RESULTS: The 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. CONCLUSION: The 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.

Pharmacological effects (gastrointestinal, respiratory and vascular) of Calligonum polygonoides: Animal model based studies.

The aim of this study was to analyze gastrointestinal, respiratory and vascular pharmacological effects of 70% hydro-alcoholic extract of Calligonum polygonoides (Cp. Cr) in animal models. All the procedures were carried-out as per previous literature with slight modification where necessary. It was found that Cp. Cr affected significant relaxation of spontaneous and K+ (80 mM) induced contractions. The results showed a corresponding shift of calcium concentration response curves. Similarly Cp. Cr showed relaxant effect on trachea in carbachol (Cch) induced tracheal contractions. Moreover, contractions induced by phenylephrine (1µM) in quarantine rabbit aortic preparations causes Cp. Cr induced relaxation of aortal contractions. Verapamil was used as a standard calcium channel blocker. The findings of this study suggested vasodilator, bronchodilator and spasmolytic effects of Cp. Cr.

Pharmacological Basis of Rumex hastatus D. Don in Gastrointestinal Diseases with Focusing Effects on H+/K+-ATPase, Calcium Channels Inhibition and PDE Mediated Signaling: Toxicological Evaluation on Vital Organs.

This present study aimed to delineate Rumex hastatus D. Don crude extract (Rh.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rh.n-Hex, Rh.ETAC, Rh.Aq) and rutin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti H. pylori, antiulcer effects, and toxicology. The preliminary phytochemical analysis of Rumex hastatus showed different phytoconstituents and shows different peaks in GC-MC chromatogram. Rumex hastatus crude extract (Rh.Cr), fractions, and rutin attributed dose-dependent (50-300 mg/kg) protection (0-100%) against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance traversed by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, Rh.Cr and Rh.ETAC caused a concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contractions at a similar concentration range, whereas Rh.n-Hex, rutin, and verapamil were relatively potent against K+-induced contractions and shifted the Ca2+ concentration-response curves (CRCs) to the right, Rh.Cr (0.3-1 mg/mL) and Rh.ETAC (0.1-0.3 mg/mL) shifted the isoprenaline-induced inhibitory CRCs to the left. Rh.n-Hex, Rh.ETAC and rutin showed anti-H. pylori effect, also shows an inhibitory effect against H+/K+-ATPase. Rumex hastatus showed gastroprotective and antioxidant effects. Histopathological evaluation showed improvement in cellular architecture and a decrease in the expression of inflammatory markers such as, cyclooxygenase (COX-2), tumor necrosis factor (TN,F-α) and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry and ELISA techniques. In RT-PCR it decreases H+/K+-ATPase mRNA levels. Rumex hastatus was found to be safe to consume up to a dose of 2000 mg/kg in a comprehensive toxicity profile. Docking studies revealed that rutin against H+/K+-ATPase pump and voltage-gated L-type calcium channel showed E-values of -8.7 and -9.4 Kcal/mol, respectively. MD simulations Molecular Mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area (MMPBSA/GBSA) findings are consistent with the in-vitro, in-vivo and docking results.

Potential biomedical applications of Araucaria araucana as an antispasmodic, bronchodilator, vasodilator, and antiemetic: Involvement of calcium channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Since pre-Columbian era, the resin of Araucaria araucana tree has been used traditionally for the treatment of ulcers and wounds. Araucaria species have also been used to treat inflammation, respiratory problems, viral infections, ulcers, and rheumatoid, cardiovascular, and neurological disorders. AIMS AND OBJECTIVE: Due to its popular use, the authors aimed to scrutinize the potential of this plant as an antispasmodic and an antiemetic agent. Furthermore broncho- and vasodilatory effects of this plant was explored to rationalize its folkloric uses. MATERIALS AND METHODS: Araucaria araucana crude extract (Aa.Cr) was evaluated in isolated preparations of rabbit jejunum, trachea, aorta, and atria to investigate the antispasmodic, bronchodilator, and vasodilator effects. The potential mechanistic approaches were compared with the standard drug 'verapamil'. The antiemetic activity was determined and compared with the standard drug 'domperidone' via chick emesis model. RESULTS: Aa.Cr dose-dependently relaxed both spontaneous and K+-induced contractions in the isolated jejunum preparations of rabbits. In concentration-response curves of calcium (Ca++), Aa.Cr also triggered the rightward shift like verapamil. Applying carbachol and phenylephrine (1 µM) and K+ (80 mM) to the isolated tracheal and aortic tissue preparation, respectively, resulted in broncho- and vasodilatory activities, respectively which may be due to the inhibition of Ca++ channels. Aa.Cr inhibited atrial force and spontaneous contractions in the rabbit's right atria. Aa.Cr exhibited significant antiemetic activity (P < 0.001 vs. saline) in dose-dependent (50-150 mg/kg) manner like domperidone. In silico molecular docking was performed to investigate the biological targets of purified components of Aa.Cr which revealed that cadinol dominantly targets ß2 receptors to cause bronchodilation, however, eudesmin binds non-specifically to all the selected targets, while secoisolariciresinol mediated high hydrogen bonding with muscarinic receptors (M1 and M3) and Ca++ channels, thus shows the suggested mechanistic pathways of targeted activities. CONCLUSIONS: The results of this study indicates that Aa.Cr may exhibit antispasmodic activity, bronchodilation, and vasodilation by inhibiting voltage-dependent Ca++ channels and release of subcellular calcium. This explains its folkloric use in hypertension, bronchospasms, gastrointestinal spasms, and emesis.

The Antispasmodic Effect of Warionia saharae Essential Oil in Experimental Models and its Mechanism of Action.

With several medicinal and aromatic species, the Asteraceae family is one of the largest angiosperm families. The genus Warionia is represented in this family by only one species, Warionia saharae. In Moroccan traditional medicine, this species is widely used to treat gastrointestinal problems. Essential oil of this plant (EoWs) was studied for possible myorelaxant and antispasmodic activities to rationalize some of the traditional uses. In this investigation, hydrodistillation was used to obtain the essential oil from the aerial part of the dry plant extract (EoWs), which was then analyzed using gas chromatography coupled to mass spectrometry (GC/MS). The major compounds identified in the EoWs are nerolidyl acetate (21.44%), ß-Eudesmol (19.47%), linalool (16.48%), 1-terpinene-4-ol (10.93%), and cineole (5.34%). EoWs is relatively safe in the case of acute intake up to 2 g/kg body weight of albino mice. The effect of EoWs on intestinal relaxation was investigated using rabbit and rat jejunal smooth muscle. We have noticed that EoWs produce a myorelaxation on basal rabbit jejunum's contractions in a concentration-dependent manner with a maximal effect at 30 µg/mL. This myorelaxation was not dependent on adrenergic receptors. When the rat jejunums were pre-contracted with 25 mM KCl or 10 µM Carbachol (CCh), EoWs had an antispasmodic action with an IC50 values of 15.76 ± 0.37 and 12.04 ± 0.30 µg/mL, respectively. Preliminary results showed that it is probable that our plant might act directly through the NO and guanylate cyclase signaling pathway and on muscarinic but not nicotinic receptors. The results reveal that the Essential oil of W. saharae appears to have an impact on intestinal relaxation in vitro conditions. This finding lends credence to the traditional usage of this plant to treat intestinal disorders.

Antidiarrheal effect of the ethanol extract from Scutellaria barbata and its effect on the contraction of jejunum smooth muscles.

Scutellaria barbata (S. barbata), a traditional herbal medicine used in southern China, possesses anti-inflammatory, antitumor, spasmolytic and expectorant effects. However, there are not many recent studies on its gastrointestinal effects. This study aimed to evaluate the antidiarrheal effect of the ethanol extract of S. barbata (SBE) and its effect on the isolated jejunum smooth muscle. METHODS: The antidiarrheal effect of SBE (doses: 125, 250 and 500 mg/kg) on castor oil-induced diarrhea was investigated in vivo. The effect of SBE (0.01-10 mg/mL) on spontaneous or acetylcholine chloride (ACh, 10µM)/KCl (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was examined in vitro. The possible spasmolytic mechanism of SBE (1 and 3mg/mL) was analyzed by accumulating CaCl2 in a Ca2+-free high-K+ (60mM) solution. RESULTS: SBE (125, 250 and 500mg/kg) could delay the initial semi-solid onset time of mice and also reduce the diarrhea index in vivo. Furthermore, SBE (0.01-10mg/mL) could alleviate the spontaneous or ACh/KCl-induced contraction in vitro. SBE (1 and 3mg/mL) also inhibited the contraction induced by CaCl2, and the concentration-response curves of CaCl2 moved downward and to the right, similar to those of verapamil (0.01 and 0.1µM). CONCLUSIONS: SBE exerts antidiarrheal and spasmolytic effects, which provides a pharmacological basis for its use in functional gastrointestinal disorders.

Antidiarrheal effect of ethanol extract from Lophatheri Herba and its effect on isolated jejunal smooth muscle in rabbits.

Lophatheri Herba is a traditional Chinese medicine, which is commonly used in the treatment of fever, stomatitis, urodynia. The aim of the study is to evaluate the antidiarrheal activity of the ethanol extract of Lophatheri Herba (Gramineae, ELH) and observe its effect on isolated jejunum smooth muscle in rabbits, so that we can provide a possible pharmacological basis for its clinical use. Methods: In vivo, the antidiarrheal activity of ELH (250, 500 and 1000 mg/kg; orally) in castor oil-induced Kun Ming mice was evaluated. In vitro, the effect of ELH (0.01-10 mg/mL) on the spontaneous and ACh (10µM)/K+ (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was studied. The possible mechanism of spasmolytic effect of ELH (1, 3mg/mL) was explored by pretreatment of intestinal tract with CaCl2. Results: ELH (500 and 1000mg/kg) exhibited antidiarrheal effect and it (0.01-10 mg/mL) inhibited the spontaneous and ACh/K+-induced contraction with an EC50 value of 1.27 (0.89-1.34), 0.76 (0.54-1.02) and 0.34 (0.27-0.53), it also shifted the concentration-response curves of CaCl2 to right with decreased in max, similar to verapamil. ELH has significant antidiarrheal and spasmolytic effect, this provides the pharmacological basis for use in gastrointestinal disorders.

Antispasmodic activity of the ethanol extract of Citrullus lanatus seeds: Justifying ethnomedicinal use in Pakistan to treat asthma and diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus lanatus (Thunb.) belongs to the ground family, Cucurbitaceae, known for edible fruit. Besides nutritional benefits, the traditional herbal practitioners in Pakistan and India used their seeds to treat gastrointestinal, respiratory, and urinary disorders. In Northern Sudan, its seeds are often used as a laxative. Its root is laxative and emetic at a high dose. Its seeds are also used to treat bedwetting and urinary tract obstruction. AIM OF THE STUDY: This study aimed to elucidate the multi-target mechanisms of Citrullus lanatus seeds to treat asthma and diarrhea. The pharmacological experiments were designed and conducted, along with the pharmacology network and molecular docking predictions, to verify the seeds biopotency for antispasmodic and bronchodilator properties. METHODS: LC ESI-MS/MS were performed to identify the potentially active compounds in hydroethanolic extract of Citrullus lanatus seeds, then to quantify them by HPLC. The quantified bioactive compounds of Citrullus lanatus, i.e., stigmasterol, quinic acid, malic acid, epicatechin, caffeic acid, rutin, p-coumaric acid, quercetin, ferulic acid, scopoletin, apigenin, and kaempferol were subjected to in silico studies for molecular docking. The hydroethanolic extract of Citrullus lanatus seeds was examined on isolated rabbit tissue, i.e., jejunum, trachea, and urinary bladder. The antiperistalsis, antidiarrheal and antisecretory studies were also performed in animal models. RESULTS: In silico studies revealed that bioactive compounds of C. lanatus seeds interfere with asthma and diarrhea-associated target genes, which are a member of calcium mediate signaling, regulation of cytosolic calcium concentration, smooth muscle contraction, and inflammatory responses. It was also found that rutin, quercetin, kaempferol, and scopoletin were stronger binding to voltage-gated calcium channels, calcium/calmodulin-dependent protein kinase, myosin light chain kinase, and phosphoinositide phospholipase C, thus, exerting calcium channel blocker activity. The hydroethanolic extract of C. lanatus seeds exerted a concentration-dependent relaxant response for the spasmolytic response on isolated jejunum and trachea preparations and caused relaxation of spastic contraction of K+ (80 mM). Furthermore, it caused a non-parallel rightward shift with suppression of calcium concentration-response curves. In animal models, the Cl.EtOH showed antiperistalsis, antidiarrheal and antisecretory response. CONCLUSION: Thus, we confirm Citrullus lanatus seeds have some medicinal effects by regulating the contractile response through target proteins of calcium mediates signaling and can be a promising component in the medical treatment for asthma and diarrhea.

Spasmolytic, Gastroprotective and Antioxidant Activities of Dry Methanol Extract of Ferula heuffelii Underground Parts.

Dry MeOH extract of Ferula heuffelii (Apiaceae) underground parts was tested for spasmolytic, gastroprotective and antioxidant activities. HPLC analysis revealed that chlorogenic acid (CGA; 34.6 mg/g) was its main constituent. Extract in vitro exhibited notable total antioxidant activity (FRAP value=1.0 µmol Fe2+ /mg), and scavenging of DPPH (SC50 =62.5 µg/ml) and • OH radicals (49.5 % at 20 µg/ml in 2-deoxyribose assay). In vitro on isolated rat ileum, extract exhibited significant spasmolytic activity, i. e., it showed 124.6 % of maximal atropine effect on spontaneous contractions (at 100 µg/ml), and reduced spasmogenic effect of KCl (80 mm) to 44.4 % (at 60 µg/ml) and of highest applied concentration of ACh to 26.3 % (at 120 µg/ml). In parallel experiments, spasmolytic effect of CGA was also demonstrated. In acute EtOH-induced gastric ulceration model in rats, extract (100 mg/kg p.o.) showed significant gastroprotective effect (gastric damage score 0.50), similar to ranitidine (20 mg/kg p.o.). Obtained results showed that tested F. heuffelii polar extract represents new herbal preparation with potential use against some gastrointestinal complaints.

Antidiarrheal and antispasmodic activities of Trillium govanianum rhizomes extract: involvement of calcium channel blockade.

The antidiarrheal effect of methanolic extract of Trillium govanianum Wall. ex D. Don (Melanthiaceae alt. Trilliaceae) was studied at doses of 12.5, 25, and 50 mg/kg in different animal models of diarrhea including castor oil (6 mL/kg), magnesium sulfate (2 gm/kg), sodium picosulfate (2 mL/kg) and lactitol (0.25 mL/kg). The antispasmodic effect of T. govanianum was studied on isolated rabbit's jejunum, using acetylcholine as tissue stabiliser and verapamil as calcium channel blocker. T. govanianum attenuated the diarrhea by producing a significant decrease in the number and weight of stool, and an increase in stool latency time. T. govanianum completely inhibited both spontaneous as well as high potassium induced contractions of isolated rabbit's jejunum, which was analogous to verapamil. Moreover, T. govanianum produced a right shift in calcium concentration response curve, confirming its calcium channel blocking activity. These findings provide scientific ground to its medicinal use in diarrhea and gut spasms.

Phytochemical Analysis, Antispasmodic, Myorelaxant, and Antioxidant Effect of Dysphania ambrosioides (L.) Mosyakin and Clemants Flower Hydroethanolic Extracts and Its Chloroform and Ethyl Acetate Fractions.

Dysphania ambrosioides (L.) Mosyakin and Clemants is an annual or ephemeral perennial herb used traditionally in the Mediterranean region in folk medicine to treat various illnesses, including those related to the digestive system. This study aims to assess the antispasmodic, myorelaxant, and antioxidant effects of D. ambrosioides flower hydroethanolic extract and its chloroform and ethyl acetate fractions in a comparative study to evaluate the result of the extraction type on the potential activity of the extract. Both rat and rabbit jejunum were used to evaluate the antispasmodic and myorelaxant effect, while the antioxidant effect was evaluated using DPPH, a ferric reducing power assay, and a beta-carotene bleaching test. LC/MS-MS analysis was carried out to reveal the composition of the different types of extract. Following the results, the hydroethanolic extract showed a significant myorelaxant effect (IC50 = 0.39 ± 0.01 mg/mL). Moreover, it was shown that the hydroethanolic extract demonstrated the best antispasmodic activity (IC50 = 0.51 ± 0.05 mg/mL), followed by the ethyl acetate (IC50 = 4.05 ± 0.32 mg/mL) and chloroform (IC50 = 4.34 ± 0.45 mg/mL) fractions. The antioxidant tests showed that the hydroethanolic extract demonstrated high antioxidant activity, followed by the ethyl acetate and chloroform fractions. The LC/MS-MS analysis indicates that the plant extract was rich in flavonoids, to which the extract activity has been attributed. This study supports the traditional use of this plant to treat digestive problems, especially those with spasms.

Antispasmodic Potential of Medicinal Plants: A Comprehensive Review.

Numerous medicinal plants have been utilized for the treatment of different types of diseases and disorders including gastrointestinal (GI) diseases. GI diseases are the most common complaints that normally affects the largest proportion of children and adolescents with overlapping clinical manifestation in diagnosis and medical needs. Drugs with antispasmodic effects are normally applied for the symptomatic treatment of contraction and cramping of smooth muscles in gastrointestinal diseases as well as in other critical clinical situations. In alternative system of medicines, the antispasmodic herbs played a significant role in the cure of GI diseases. These medicinal plants and their herbal products are used from generation to generation because of multiple nutritional and therapeutic benefits. The multiple uses might be attributed to the presence on biologically active chemical constitutes. The main aim of this review is to focus on the medicinal potential of plants possessing antispasmodic activities with their proposed mechanism of action. Several databases such as Google Scholar, Cochrane database, Scopus, and PubMed were used to search the relevant literature regarding "plants with antispasmodic activities." This present study highlights the updated and quantified information on several medicinal plants with antispasmodic activity like Zanthoxylum armatum, Matricaria chamomilla, Foeniculum vulgare, Pycnocycla spinosa, Atropa belladonna, Lavandula angustifolia, Mentha pulegium, Glycyrrhiza ularensis, Anethum graveolens, and Origanum majorana. Moreover, recent studies on other medicinal plant species also have been included in this review article. Additionally, the study also revealed that the active compounds of all these plants possess significant spasmolytic effect which is safest, efficacious, and cost effective as compared to the available synthetic drugs.

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility.

The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in ß-PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if ß-PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a ß-PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a trace-amine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous ß-PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of ß-PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through ß-PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus.

Myorelaxant and antispasmodic effect of an aqueous extract of Artemisia campestris L. via calcium channel blocking and anticholinergic pathways.

Intestinal spasms are violent contractions that occur in the intestine, which cause discomfort to people who have them. Medicinal plants are widely used in traditional Moroccan medicine to treat these problems, among these being Artemisia campestris L. This study aims to evaluate the relaxant and antispasmodic effects of an aqueous extract of this plant (ACAE). It was performed in vitro on isolated segments of both isolated rat and rabbit jejunum mounted in an organ bath and tension recordings made via an isotonic transducer. ACAE caused a myorelaxant effect on baseline rabbit jejunum contractions in a dose-dependent and reversible manner with an IC50 of 1.52 ± 0.12 mg/ml. This extract would not act via adrenergic receptors pathway. On the other hand, the extract caused a dose-dependent relaxation of the jejunum tone in rat jejenum segments pre-contracted with either Carbachol (CCh; 10-6 M) or high K+ (KCl 75 mM) with an IC50 = 0.49 ± 0.02 mg/ml and 0.36 ± 0.02 mg/ml respectively. In the presence of different doses of the extract, the maximum response to CCh and CaCl2 was significantly reduced. This demonstrates that ACAE acts on both muscarinic receptors and voltage-dependent calcium channels. Thus, the plant extract acted on both muscarinic and nicotinic receptors and acts on the guanylate cyclase pathway, but not the nitric oxide pathway. These results indicate the mechanism by which Artemisia campestris L. acts as an effective antispasmodic agent in traditional Moroccan medicine.

Antispasmodic activity and mechanism of action of polyherbal formulation DCD-684 on rabbit jejunum.

Digas colic drops (DCD-684) is a polyherbal formulation containing decoctions of five medicinal plants namely Carum carvi L., Foeniculum vulgare Mill, Mentha arvensis L., Mentha piperita L. and Zingiber officinale Roscoe. These plants have been extensively used in traditional medicine for the treatment of various gastrointestinal diseases including abdominal colic. This study was conducted to determine the spasmolytic effect of DCD-684 (100% v/v) and its individual plant components on isolated rabbit jejunum (in vitro) and their possible mechanism of action. The effects were evaluated on spontaneous and pre-contracted tissues using KCl (80mM) and other contractile agonists including acetylcholine (0.3µM), carbamylcholine (0.3µM), serotonin (10 µM) and histamine (100µM) in the presence and absence of DCD-684. The various concentrations of DCD-684 (0.1-3% v/v) demonstrated spasmolytic effects on both spontaneous (IC50=0.75%) and KCl-induced contractions (IC50=1.6%), respectively. It also inhibited the contractions induced by acetylcholine (IC50=0.45%), carbamylcholine (IC50=0.95%), serotonin (IC50=0.95%) and histamine (IC50=0.87%). The DCD-684 exhibited synergistic effect due to its five plant components suggesting that spasmolytic cascade is probably governed by muscarinic and/or nicotinic receptors, serotonergic histaminergic, as well as calcium channel blocking mechanisms. Thereby, providing the pharmacological basis of its therapeutic use in the gastrointestinal motility disorders and related inflammatory ailments.

GC/MS analysis, anti-leishmanial and relaxant activity of essential oil of Chenopodium ambrosioides (L.) from Malakand region.

Chenopodium ambrosioides is abundantly available in Malakand region. As constituents and concentrations of essential oils vary based on its geographical location, we carried our current study to extract and evaluate its possible relaxant activity in rabbits' jejunum and anti-leishmanial activity against promastigotes of Leishmania tropica. The essential oil was obtained from aerial fresh parts through steam distillation followed by GC/MS analysis. Antispasmodic activity was performed on spontaneous and KCl induced contractions. Curves for calcium concentration response (CCRCs) were prepared with and without different concentrations of essential oils and verapamil - a standard calcium channel blocker as per our reported procedures. GC/MS analysis indicated that the essential oil contains 4-carene (56.59%) and o-cymene (41.46%), the two most abundant compounds previously reported from this species. The LD50 value for acute toxicity is 279.66±2.2mg/kg. The essential oil have significant antileishmanial activity with LC50 of Log10 (1.83±0.0026) ×10-6mg/ml, potent relaxant activity on rabbits' jejunal preparations with respective EC50 = 1.46±0.15mg/ml for spontaneous activity. For KCl (80mM) induced contractions, EC50=0.26±0.02mg/ml. In CCRCs, the oil produced a right shift as exhibited by verapamil. More, its relaxant activity, which is mediated through calcium channel blocking mechanism, proves a rationale for its traditional use in gut spasm.

Investigation of antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of Brazilian Cannabis sativa L. roots in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies are performed with the aerial parts of Cannabis sativa L. (Cannabaceae). However, roots remain poorly studied, despite citations in the scientific literature. The C. sativa roots are indicated for the treatment of pain, inflammation, fever, among other health problems. AIM OF THE STUDY: This study aimed to evaluate the antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of C. sativa roots in experimental models using mice and rats. MATERIAL AND METHODS: The chemical composition of the aqueous extract of C. sativa roots (AECsR) was evaluated by LC-MS. The antinociceptive activity was assessed in mice by the induction of writhing with acetic acid, paw licking with formalin, and reactivity in the hot plate test. Fever was induced by the administration of a suspension of Saccharomyces cerevisiae in young rats. The asthmatic activity was performed with ovalbumin (OVA)-immunized mice with cellular and histological analysis. Finally, the spasmolytic activity was performed using mice isolated trachea. For in vivo studies, the doses were 12.5, 25, or 50 mg/kg whereas for in vitro, the concentration of AECsR was 729 µg/mL. RESULTS: From the LC-MS data, we identified p-coumaroyltyramine, feruloyltyramine canabissativine in AECsR. The extract promoted a reduction of writhing in all tested doses (12.5, 25, or 50 mg/kg). Similarly, it reduced the pain in the formalin test at doses of 12.5 and 50 mg/kg (first phase) and 12.5 and 25 mg/kg (second phase). In the hot plate test, the doses of 12.5, 25, and 50 mg/kg promoted antinociceptive effect at different times, and the lowest dose maintained its action in the analyzes performed at 60, 90, and 120 min after administration. The anti-inflammatory activity of AECsR was observed in the mouse model of asthma, reducing the total leukocyte count in the bronchoalveolar fluid (BALF) at a dose of 25 mg/kg, as well as reducing eosinophilia in all tested doses (12.5, 25, and 50 mg/kg). Histological analysis of lungs stained with H&E and PAS showed a reduction in the number of inflammatory cells in the perivascular and peribronchial region, as well as reduced mucus production. CONCLUSION: The results suggest that AECsR promotes pain control, either by a central or inflammatory mechanism, and has antiasthmatic activity. However, there was no antipyretic or spasmolytic effect.