Isolated Rat Ileum Research Articles

Antispasmodic Activity of Light-Roasted Coffee Extract and Its Potential Use in Gastrointestinal Motility Disorders.

Antispasmodic agents are crucial in managing gastrointestinal motility disorders by modulating muscle contractions and reducing symptoms like cramping and diarrhea. This study investigated the antispasmodic potential of different coffee bean extracts, including light coffee (LC), medium coffee (MC), and dark coffee (DC), on ileum contractions induced by potassium chloride (KCl), and elucidated their mechanisms of action using in vitro isolated tissue techniques. The results demonstrated that all coffee extracts reduced spontaneous contractions of rat ileum tissue in a dose-dependent manner. Among these, LC showed the most significant reduction in ileum contractions, particularly at higher concentrations. The key findings reveal that LC at 5 mg/mL significantly reduced CaCl2-induced contractions in isolated rat ileum tissue, indicating that LC may inhibit calcium influx or interfere with calcium signaling pathways. The presence of nifedipine, propranolol, and N-nitro-L-arginine methyl ester (L-NAME) have been confirmed in their involvement; they block calcium influx and calcium channels and activate β-adrenergic pathways as part of LC's mechanism of action. The presence of their active compounds, particularly chlorogenic acid and caffeine, likely contributes to the observed antispasmodic effects. These findings suggest that LC exerts its antispasmodic effects by targeting key mechanisms involved in muscle spasms and intestinal motility, providing a potential for managing such conditions.

Calcium Channel Inhibitory Effect of Marjoram (Origanum majorana L.): Its Medicinal Use in Diarrhea and Gut Hyperactivity.

The leaves of Origanum majorana (O. majorana) are traditionally renowned for treating diarrhea and gut spasms. This study was therefore planned to evaluate its methanolic extract. Gas chromatography-mass spectrometry (GC-MS) was used to identify the phytochemicals, and Swiss albino mice were used for an in vivo antidiarrheal assay. Isolated rat ileum was used as an ex vivo assay model to study the possible antispasmodic effect and its mechanism(s). The GC-MS analysis of O. majorana detected the presence of 21 compounds, of which alpha-terpineol was a major constituent. In the antidiarrheal experiment, O. majorana showed a substantial inhibitory effect on diarrheal episodes in mice at an oral dosage of 200 mg/kg, resulting in 40% protection. Furthermore, an oral dosage of 400 mg/kg provided even greater protection, with 80% effectiveness. Similarly, loperamide showed 100% protection at oral doses of 10 mg/kg. O. majorana caused complete inhibition of carbachol (CCh, 1 µM) and high K+ (80 mM)-evoked spasms in isolated ileal tissues by expressing significantly higher potency (p < 0.05) against high K+ compared to CCh, similar to verapamil, a Ca++ antagonist. The verapamil-like predominant Ca++ ion inhibitory action of O. majorana was further confirmed in the ileal tissues that were made Ca++-free by incubating the tissues in a physiological salt solution having ethylenediaminetetraacetic acid (EDTA) as a chelating agent. The preincubation of O. majorana at increasing concentrations (0.3 and 1 mg/mL) shifted towards the right of the CaCl2-mediated concentration-response curves (CRCs) with suppression of the maximum contraction. Similarly, verapamil also caused non-specific suppression of Ca++ CRCs towards the right, as expected. Thus, this study conducted an analysis to determine the chemical constituents of the leaf extract of O. majorana and provided a detailed mechanistic basis for the medicinal use of O. majorana in hyperactive gut motility disorders.

Spasmolytic Activity of Gentiana lutea L. Root Extracts on the Rat Ileum: Underlying Mechanisms of Action

The roots of Gentiana lutea L. are utilized in the preparation of various beverages and herbal remedies, serving as a traditional remedy for gastrointestinal ailments. The spasmolytic activity that could substantiate the traditional use of G. lutea root had not been investigated. The main objective goal of the study was to determine the validity of its use as a traditional remedy. The extraction of G. lutea root was performed using a 50% hydroethanolic solvent with three different extraction techniques: ultrasound-assisted extraction (UAE), heat-assisted extraction, and percolation. The spasmolytic activity was tested on isolated rat ileum. The mechanism of action was monitored using the models of spontaneous contractions and acetylcholine-, histamine-, CaCl2-, Bay K8644-, L-NAME-, ODQ-, apamin-, BaCl2-, charybdotoxin-, glibenclamide-, TRAM-34-, and quinine-modified contractions. UAE, having the best bioactivity, was further subjected to a liquid–liquid extraction fractionation. HPLC phytochemical analysis was performed for all tested extracts and fractions. Gentian root extracts were rich in secoiridoids, xanthones, and flavonoids. The UAE has shown better results on spontaneous contractions in comparison to its fractions, leading to the more detailed testing of its spasmolytic mechanism of activity. The extract’s activity is primarily mediated through intermediate conductance Ca2+-activated K+ channels, ATP-sensitive K+ channels, voltage-sensitive K+ channels, and mechanisms that activate Ca2+ channels. Overall, the G. lutea root shows great potential in the treatment of spasmodic gastrointestinal ailments.

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

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. 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. 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 β-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, β-amyrin had a stronger interaction with the two proteins during the simulation. The isolated compounds boonein and β-amyrin could serve as starting materials for the development of antispasmodic drugs.

Synthesis and Evaluation of Some New Pyridines as Possible P-gp Inhibitors with Reduced Calcium Channel Blocking Activity

The 1,4-dihydropyridine derivatives (DHPs) (3a-b and 4a-c) were oxidized with iodine in methanol to produce five new, hitherto unreported pyridine derivatives (5a-b and 6a-c). The “Everted sac method” was used to assess the DHPs and their pyridines for potential p-glycoprotein (P-gp) inhibitory or multidrug resistance reversal action. Domperidone, a P-gp substrate, was examined for intestinal absorption in everted rat jejunal segments in the presence and absence of DHPs (3a-b and 4a-c) and pyridines (5a-b and 6a-c) at doses of 30 μg/mL and 100 μg/mL. The standard was Verapamil, a known P-gp inhibitor (30 μg/mL and 100 μg/mL). The P-gp inhibition of all the tested compounds was higher than Verapamil. The P-gp inhibition of compounds 5b and 6b was the highest. Utilizing isolated rat ileum, the newly synthesized pyridine derivatives calcium channel blocking efficacy was also investigated. The strongest Ca2+ channel-blocking action was seen with compound 5b. It was determined to be equivalent to Nifedipine, the gold standard. Strong P-gp inhibitor compound 6b has little calcium channel-blocking action.

Antidiarrheal and Antispasmodic Effects of Ethanolic Stem Bark Extract of ‎Boswellia ‎dalzielii H. in Wistar Rats

The modulatory potentials of the ethanolic stem bark extract of Boswellia dalzieliiH. on diarrhea and gastrointestinal motility was investigated in rats. Antidiarrheal activity was evaluated in castor oil induced model using 25 inbreed, overnight fasted rats divided into five groups (A-E). Intestinal motility was determined using Charcoal transit time in 25 overnight fasted rats divided equally into five groups (A-E). Graded doses of the plant extract(100,200 and 400mg/kg respectively) were given to groups B, C and D, while group A served as vehicle control (VEH) (distilled water) and group E served as Atropine control(0.1mg/kg). Antispasmodic activity of the plant extract was determined with 3cm piece of isolated rat ileum incubated in a thermostatically regulated organ bath. The set-up allows for in vitro assessment of intestinal motility with atropine and acetylcholine as standard drugs for cholinergic muscarinic receptor potentials. The ethanolic stem bark extract of Boswellia dalzielli H significantly (P&lt; 0.0001) and dose dependently reduced castor oil induced diarrhea and activated charcoal transit time in rats. The plant extract significantly (P&lt;0.05) and dose dependently inhibited acetylcholine induced contractility of isolated ileac segments of rats when compared to controls. The ethanolic stem bark extract of Boswellia dalzielii H causes delay in gastrointestinal contractions via the inhibition of muscarinic cholinergic receptors in rats.

A Comparative Evaluation of Various Therapies of Synthetic Drugs with Amla and Honey Combination for the Treatment of Gastroesophageal Reflux Disease

Abstract: Background: Gastroesophageal Reflux Disease (GERD) is disorder of oesophagus that causes ulcer and erosion. Materials and Methods: A comparison based on the in vivo study was carried out to determine the therapeutic efficacy of herbal formulation using Amla and Honey in combination with Pantoprazole and Rebamipide for the treatment of GERD. The effects of all above mentioned medications were also checked on intestinal motility. In vitro studies were carried out to determine the antispasmodic activity of Amla and Honey in comparison to acetylcholine by isolated rat ileum. In pylorus ligation GERD model, mono-therapy was performed by giving herbal formulation of Amla and Honey. In combination therapy Pantoprazole and Rebamipide, Amla and Honey with Pantoprazole and Rebamipide were given and their therapeutic efficacy was observed at the ends of 14 days. In charcoal meal motility test the distance travelled by charcoal in intestine was measured. Results and Discussion: Combination therapy have highest therapeutic efficacy in comparison to mono-therapy of natural combination of Amla and Honey against Pantoprazole and Rebamipide. In vitro antispasmodic activity revealed that Amla and Honey formulation decreased the contractility pattern in concentration dependent manner against acetylcholine. In charcoal meal motility test highest intestinal motility were observed in Amla and Honey and can be given in GERD for easily digestion of food from stomach. Conclusion: Herbal combination of Amla and Honey in comparative evaluation decreases the Gastroesophageal reflux disease, intestinal mobility, and show anti-spasmodic activity in isolated rat’s ileum. However, these combinations serve as a more potential agent for decreasing all the factors responsible for the reflux disease. Keywords: Combination therapy, Mono-therapy, Pantoprazole, Rebamipide, Mucosal.

The Detailed Pharmacodynamics of the Gut Relaxant Effect and GC-MS Analysis of the Grewia tenax Fruit Extract: In Vivo and Ex Vivo Approach.

The study was performed to assess and rationalize the traditional utilization of the fruit part of Grewia tenax (G. tenax). The phytoconstituents present in the methanolic extract were analyzed using Gas-Chromatography-Mass Spectroscopy (GC-MS), while the anti-diarrheal activity was investigated in the Swiss albino mice against castor oil-provoked diarrhea in vivo. The antispasmodic effect and the possible pharmacodynamics of the observed antispasmodic effect were determined in an isolated rat ileum using the organ bath setup as an ex vivo model. GC-MS findings indicate that G. tenax is rich in alcohol (6,6-dideutero-nonen-1-ol-3) as the main constituent (20.98%), while 3-Deoxy-d-mannoic lactone (15.36%) was detected as the second major constituents whereas methyl furfural, pyranone, carboxylic acid, vitamin E, fatty acid ester, hydrocarbon, steroids, sesquiterpenes, phytosterols, and ketones were verified as added constituents in the methanolic extract. In mice, the orally administered G. tenax inhibited the diarrheal episodes significantly (p < 0.05) at 200 mg/kg (40% protection), and this protection was escalated to 80% with the next higher dose of 400 mg/kg. Loperamide (10 mg/kg), a positive control drug, imparted 100% protection, whereas no protection was shown by saline. In isolated rat ileum, G. tenax completely inhibited the carbamylcholine (CCh; 1 µM) and KCl (high K+; 80 mM)-evoked spasms in a concentrations-mediated manner (0.03 to 3 mg/mL) by expressing equal potencies (p > 0.05) against both types of evoked spasms, similar to papaverine, having dual inhibitory actions at phosphodiesterase enzyme (PDE) and Ca2+ channels (CCB). Similar to papaverine, the inhibitory effect of G. tenax on PDE was further confirmed indirectly when G. tenax (0.1 and 0.3 mg/mL) preincubated ileal tissues shifted the isoprenaline-relaxation curve towards the left. Whereas, pre-incubating the tissue with 0.3 and 1 mg/mL of G. tenax established the CCB-like effect by non-specific inhibition of CaCl2−mediated concentration-response curves towards the right with suppression of the maximum peaks, similar to verapamil, a standard CCB. Thus, the present investigation revealed the phytochemical constituents and explored the detailed pharmacodynamic basis for the curative use of G. tenax in diarrhea and hyperactive gut motility disorders.

A Comparative Study on Mono-therapy and Combination Therapy of Additive Drugs (Rebamipide and Pantoprazole) with Amla and Honey combination for the Treatment of Gastroesophageal Reflux Disease and Intestinal motility

Gastroesophageal reflux disease (GERD) is digestive disorder of oesophagus. Reflux of food damage oesophagus and cause oesophageal ulcer and erosion. The treatment strategy starts by giving natural formulation and synthetic drugs. A comparison based on In-vivo study was carried out to determine the therapeutic efficacy of herbal formulation using Amla and Honey in combination with Pantoprazole and Rebamipide for the treatment of GERD, The effects of all above mentioned medication was also checked on intestinal motility. In vitro studies were carried out to determine the antispasmodic activity of Amla and Honey in comparison to acetylcholine by isolated rat ileum. In pylorus ligation GERD model mono-therapy was performed by giving herbal formulation of Amla and Honey. In combination therapy Pantoprazole and Rebamipide, Amla, Honey with Pantoprazole and Rebamipide were given and their therapeutic efficacy was observed at the ends of 14 days. In charcoal meal motility test the distance travelled by charcoal in intestine was measured. At the end of study it was concluded that combination therapy have highest therapeutic efficacy in comparison to mono-therapy of natural combination of Amla and Honey against Pantoprazole and Rebamipide. In In-vitro antispasmodic activity Amla and Honey formulation decreased the contractility pattern in concentration dependent manner against acetylcholine. In charcoal meal motility test highest intestinal motility were observed in Amla and Honey and can be given in GERD for easily digestion of food from stomach.

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

AbstractDry 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.

GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica.

This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. The phytochemicals were detected using gas chromatography–mass spectrometry (GC–MS) while the in vivo antidiarrheal test was done using Swiss albino mice. To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. GC–MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. The highest antidiarrheal effect was observed with loperamide (p < 0.01), used as a control drug. In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders.

EFFECT OF PUDINA ARKA (HYDRO DISTILLATE OF MENTHA) ON RAT ILEUM, AGAINST ACETYL CHOLINE INDUCED CONTRACTIONS

Introduction: Pudina or Mint or Meantha viridis is an important drug used in traditional systems of medicines to treat Stomachache, Dyspepsia, Indigestion, tastelessness, colic pain etc. Pudina and its distillate (Arka) has been indicated in classics to treat Chhardi (Vomiting), Ajeerna (Indigestion), Adhamaana (Flatulence), Udarshoola (Stomachache), Mandagni (Low appetite /digestive fire) and colic pain. Isolated tissue bath study is a classical and best way to evaluate the effect of any medication on smooth muscles. The present study was aimed on To evaluate the effect of Pudina Arka on isolated smooth muscle of rat ileum. Material and methods: Sample of Pudina Arka was prepared in the Departmental Lab, PG Department of Rasashastra &amp; Bhaishajya Kalpana, National Institute of Ayurveda, Jaipur. Isolated rat ileum was set on organ bath assembly in Tyrode solution with maintain the temperature at 37OC, Oxygen and nutrition. Contraction was induced by Acetylcholine. Then the response of Pudina Arka was observed at the dose of 0.5 ml, 1 ml, 1.5 ml and 2 ml/ 40 ml Tyrode solution. Observations and Results: Relaxations were observed on all the doses of Pudina Arka against the contraction induced by Acetylcholine. The Effective Concentration for 50% effect (EC50) was found 0.0165 ml/ml. Conclusion: Pudina Arka has antispasmodic or relaxant effect on smooth muscles of ileum. .

Effects of dibenzylbutyrolactone lignans arctigenin and trachelogenin on the motility of isolated rat ileum

Dibenzylbutyrolactone-type lignans are phenolic compounds of medical importance. The purpose of the study was to determine the effects of two such lignans, arctigenin and trachelogenin on the motility of isolated rat ileum and obtain indications on their mechanism of action. They were isolated from Arctium lappa and Cirsium arvense, respectively, which have been used traditionally to treat gastrointestinal disorders. 1–1.5 cm long segments of distal ileum were obtained from adult male Wistar rats. The intestinal segments were suspended vertically in a well-aerated organ-bath according to Magnus mounting method. The intestinal motility was monitored for 30 min before treatment to obtain the baseline, followed by treatment with 1 µM, 10 µM, 20 µM and 40 µM concentrations of arctigenin and 0.5 µM, 1 µM, 10 µM and 20 µM of trachelogenin concentrations. The amplitude, tone, and period of spontaneous contractions were measured after 15 and 30 min of treatment. To investigate their mechanism of action, cholinergic, glutamatergic, adrenergic antagonists and compounds inhibiting nitric oxide synthase and L-type calcium channels were also tested. Arctigenin and trachelogenin decreased the frequency of contractions in a dose-dependent manner. At the concentration of 20 µM and 40 µM of trachelogenin and arctigenin, respectively, there was a marked alteration in spontaneous contraction pattern with an observable increase in the period time. This activity was comparable to 0.5 µM nifedipine (L-type calcium channel blocker) treatment. Our results demonstrate relaxant effect of arctigenin and trachelogenin on the ileum motility that may be mediated by L-type calcium ion channel blockade.

Experimental evidence in support of the biological effects and physical basis of homeopathic potencies

Background: Homeopathic potencies 12 cH and above cross the Avogadro number and, for this, do not contain any original drug molecules. Two major problems involved in the scientific study of potencies are (1) understanding the physical basis of potencies and (2) demonstrating the biological effects of potencies. The present study aims to address these questions.&#x0D; Methods and Results: In course of our experimental studies spanned over more than 30 years we have demonstrated significant effects of homeopathic potencies on man, animals and plants. We have also showed that potencies could be differentiated through their electronic spectra, and this difference in spectra can be attributed to the electron transfer interaction. In a molecular complex, electron of one molecule absorbs a quantum of visible radiation and is excited, not to a higher energy level of this molecule, but to one of the vacant high energy levels of the neighboring molecules. This process is known as electron or charge transfer interaction. This has been demonstrated in Iodine ө in two different solvents of CCl4 and aqueous ethanol (Sukul N C, Environ Ecol 17,866-872, 1999). We have further demonstrated that the effect of a homeopathic potency can be transmitted from one part of a plant to another, and also from one plant to another through water. I am presenting here a few selected cases of our experimental studies. Potentized Nux vomica significantly reduced ethanol consumption in rats by 73.7%and ethanol-induced sleep time in albino mice by 44.4%. Causticum 30 C and Rhus tox 30 C produced anti-inflamatory and anti-nocicptive effect on adjuvant arthritis in albino rats. Potentized homeopathic drugs reduced microfilaraemia by 28 to 100% and filariasis in two villages of West Bengal endemic for Bancroftian filaiasis. Potentized Cina and Thuja ameliorated trichinellosis in mice reducing larval population in muscles by 84% and 68%, respectively.&#x0D; Potencies of Agaricus and Nux vomica, produced excitatory effect on the isolated rat ileum. Potentized drugs altered firing rate of hypothalamic neurons in rats and cats. Nux vom 30 c and Merc cor 30c facilitated water permeability in erythrocytes of catfish in a test tube. Potencies of Merc cor and Merc iod enhanced α-amylase activity in vitro ,by 44 and 21%,respectively.&#x0D; Drugs ,that inhibit photosynthesis and plant growth in high doses, promote the same phenomena when applied on plants at ultra low doses. Potentized Cantharis, a homeopathic drug used for burn injuries, counter the effect of heat shock in Adhatoda vasica plants in terms of modulating the expression of heat-shock proteins in the plants. The effect of heat shock and of Cantharis treatment could be transmitted from one plant to another through water. The global network of surface water in a closed system is thought to be responsible for producing this effect. Several potentized homeopathic drugs show distinct variation from each other in their absorption spectra in ultra violet region of light. These drugs when mixed with sucrose solution, also show marked differences from each other at temperatures as low as 4 0 C and as high as 70 0 C. Electron transfer interaction may contribute to the characteristic spectral properties of a homeopathic potency.&#x0D; Conclusions: Homeopathic potencies could be detected and differentiated by their electronic spectra. Potencies show marked effect on animals, plants, ex vivo effect on isolated organs and in vitro effect on enzymes.&#x0D; Keywords: Homeopathic potencies, electronic spectra, ethanol intake, adjuvant arthritis, filariasis, Cantharis, Nux vomica

High dilutions of homeopathic remedies induce relaxation of rat aorta precontracted with Noradrenalin

BACKGROUND&#x0D; Homeopathic potencies have been reported to produce alteration of contraction in isolated rat ileum in an organ bath. Potentized homeopathic drugs like Lycopus V and Aurum met are used for the treatment of hypertension. &#x0D; AIM&#x0D; The purpose of this study is to see whether Lycopus V 30 CH and Aurum met 30 CH could produce relaxation of isolated rat aorta in the organ bath.&#x0D; METHODS&#x0D; The aorta of rats were dissected out, placed in Krebs-Henseleit solution, cleared of connective tissue and endothelium and cut into 2-2.5 mm long rings. The rings were fixed in organ baths with the upper end connected by a string to an isometric transducer which was finally attached through a data acquisitation equipment to a computer. Aurum met 30 CH Lycopus V 30 CH, and their medium 90% ethanol were added separately to the bathing fluid containing the aorta rings which were precontracted with noradrenalin (NA).&#x0D; RESULTS&#x0D; Both the drugs produced significant relaxation of the aorta (p

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

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

Antispasmodic Effect of Asperidine B, a Pyrrolidine Derivative, through Inhibition of L-Type Ca2+ Channel in Rat Ileal Smooth Muscle.

Antispasmodic agents are used for modulating gastrointestinal motility. Several compounds isolated from terrestrial plants have antispasmodic properties. This study aimed to explore the inhibitory effect of the pyrrolidine derivative, asperidine B, isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178, on spasmodic activity. Isolated rat ileum was set up in an organ bath. The contractile responses of asperidine B (0.3 to 30 µM) on potassium chloride and acetylcholine-induced contractions were recorded. To investigate its antispasmodic mechanism, CaCl2, acetylcholine, Nω-nitro-l-arginine methyl ester (l-NAME), nifedipine, methylene blue and tetraethylammonium chloride (TEA) were tested in the absence or in the presence of asperidine B. Cumulative concentrations of asperidine B reduced the ileal contraction by ~37%. The calcium chloride and acetylcholine-induced ileal contraction was suppressed by asperidine B. The effects of asperidine B combined with nifedipine, atropine or TEA were similar to those treated with nifedipine, atropine or TEA, respectively. In contrast, in the presence of l-NAME and methylene blue, the antispasmodic effect of asperidine B was unaltered. These results suggest that the antispasmodic property of asperidine B is probably due to the blockage of the L-type Ca2+ channel and is associated with K+ channels and muscarinic receptor, possibly by affecting non-selective cation channels and/or releasing intracellular calcium.

Antidiarrheal activity of aqueous extract of leaves of Euphorbia hirta L.

Context: Euphorbia hirta L. is widely distributed in the Indian subcontinent and has many ethnomedicinal uses. Traditionally, the leaves of E. hirta have been used as antidiarrheal agents, for bronchial and respiratory diseases and against conjunctivitis. Aims: To evaluate the antidiarrheal activity of the aqueous extract of leaves of Euphorbia hirta. Methods: Steam and aqueous extracts of leaves of E. hirta were evaluated for their antidiarrheal activity by in vitro antiprotozoal and antimicrobial activity testing, in vivo evaluation of % protection against diarrhea in castor-oil induced rat diarrhea model, gastrointestinal transit and enteropooling assays in rat model and ex vivo tissue contractility studies. Results: Steam and aqueous extracts of leaves of E. hirta demonstrated antiprotozoal activity against Entamoeba histolytica and Giardia lamblia with MICs ranging from 31.25-62.5 µg/mL to 125-250 µg/mL. Both the extracts showed antibacterial activity against Salmonella abony, Escherichia coli and Shigella boydii. In vivo antidiarrheal activity evaluation in castor-oil induced diarrhea model in rats revealed that the steam extract at a dose of 1621 mg/kg body weight (b.w.) produced % inhibition in defecation comparable to loperamide (4 mg/kg b.w.). Aqueous extract produced significant reduction in fecal output when compared to the untreated control group (p&lt;0.05). However, the extracts failed to have any significant effect on the gastrointestinal transit of charcoal meal in rats. Also, gastric fluid accumulation was significantly reduced by steam extract at 2162 mg/kg b.w. and aqueous extract at 100 mg/kg b.w. (p&lt;0.05) when compared to the untreated group. The smooth muscle relaxation produced by the steam extract on the isolated rat ileum was comparable to that produced by atropine (0.05-0.4 µg/mL). Conclusions: The results of this study provide support for the traditional use of Euphorbia hirta leaves as an antidiarrheal agent.

Pharmacological potential of Thymus serpyllum L. (wild thyme) extracts and essential oil: A review

In traditional medicine Thymus serpyllum L. (wild thyme) herb represents a part of a large number of herbal medicinal formulations such as syrups, tinctures, infusions, teas, and decoctions. In recent years, there has been a growing interest in testing the biological properties of wild thyme, because the plant is a high-quality raw material, rich in essential oil and pharmacologically active polyphenolic compounds, which can be included in various formulations in the pharmaceutical, cosmetic, food, and chemical industries. Wild thyme extracts and essential oil have shown significant nitric oxide, ABTS and DPPH radicals scavenging potential, ferrous ion chelating property, reducing activity and ability to inhibit peroxidation of deoxyribonucleic acid (DNA), proteins and lipids. Wild thyme extracts exerted antibacterial activity against Bacillus cereus, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Salmonella enterica, Yersinia enterocolitica, as well as Lactic acid bacteria. Wild thyme essential oil has shown antibacterial potential against E. coli, L. monocytogenes, P. aeruginosa, S. enteritidis, S. aureus, Streptococcus salivariu, S. mutans, S. sanguinis, S. pyogenes, E. feacalis, B. cereus, B. subtilis, B. pumilis, Lactobacillus acidophilus, Proteus mirabilis, Klebsiella pneumoniae, Salmonella choleraesuis, and Salmonella poona. T. serpyllum extract possesses antifungal activity against Fusarium solani, F. moniliforme, Aspergillus flavus, Microsporum canis, Alternaria species, Candida albicans, and C. glabarata. The essential oil efficiently inhibited the growth of C. albicans, C. glabrata and Aspergillus fungi. Depending on the concentration, wild thyme extract significantly relaxed spontaneous contractions, as well as acetylcholine-, potassium chloride-, barium chlorideand calcium chloride-induced contractions of the isolated rat ileum. The extract significantly reduced the expression of the inducible enzyme cyclooxygenase-2 and inhibited acetylcholinesterase, myeloperoxidase and α-glucosidase activity. T. serpyllum extract has shown cytotoxic activity on human breast cancer cell lines, while essential oil has shown the antitumor potential in human cell lung cancer, colon, cervical, hepatocellular, prostate, and breast adeno-carcinoma.

Effects of Steganotaenia Araliacae Root Extract on Contractile Function of Isolated Rat Ileum

Background: Various parts of a small tree, Steganotaenia araliacaeare used as medicine in local traditional settings in Zambia to initiate and augment parturition although very little is documented about its physiological and pharmacological effects. Steganotaenia araliacaecold extract has been observed to cause contractions of uterus in rats but its effect on non-uterine muscle is unclear. The aim of this study was to establish the contractile effect of Steganotaenia araliacaecold extract on isolated rat ileum smooth muscle.Method: Animals were sacrificed by cervical dislocation. Abdominal incisions were made to expose and dissect three ileum segments from each rat. The ileum segments were immediately transferred and mounted in the organ bath containing Tyrode solution. The contractile effects of acetylcholine (a reference agonist) and Steganotaenia araliacaecold extract on ileum segments were investigated starting with the least effective doses, thereafter doubling the doses until maximal tissue response was observed. Antagonists that include atropine, indomethacin, mepyramine, ondansetron and nifedipine in the presence and absence of Steganotaenia araliacaecold extract were also investigated to establish the mechanism of actionResults: Steganotaenia araliacaecold extract increased the contractile force of isolated rat ileum in a dose-response manner but had no significant effects on the frequency of the spontaneous contractions. Pre-treating the tissue with atropine, indomethacin, mepyramine or ondansetron did not inhibit the contractile force of Steganotaenia araliacaecold extract, while pre-treating the tissue with nifedipine inhibited its contractile force by 100% (p&lt;0.05)Conclusion: The cold root extract of Steganotaenia araliacae induced contractions on isolated rat ileum smooth muscle in a dose response manner by probable activation of calcium channels. It is possible that SAEᶜif used in high doses may cause severe abdominal cramps an effect that needs to be noted as it is being used in parturition.