Contraction Of Guinea Pig Ileum Research Articles

Anti-spasmodic and Gastroprotective Activities of Harungana madagascariensis Leaf: A Traditional Anti-diarrhoea Remedy

Pharmacognosy Research,2022,14,4,492-498.DOI:10.5530/pres.14.4.71Published:October 2022Type:Original ArticleAuthors:Adaobi C. Ezike, Nwoyi N. Bassey, Emenike C. Amah, Daniel U. Nwankpa, Aniebiet E. Samuel, and John O. Medewase Author(s) affiliations:Adaobi C. Ezike*, Nwoyi N. Bassey, Emenike C. Amah, Daniel U. Nwankpa, Aniebiet E. Samuel, John O. Medewase Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu, NIGERIA. Abstract:Background: Harungana madagascariensis Lam. ex Poir. (Hypericaceae) leaf extract is used by some communities in the Niger Delta to treat diarrhoea, ulcers, and wounds. Objectives: This study investigated the antispasmodic, antimotility and gastroprotective properties of methanol:dichloromethane (1:1) extract of H. madagascariensis leaves (HME). Materials and Methods: The antispasmodic activity was evaluated in vitro using actions on contractions of guinea pig ileum and rabbit jejunum provoked by spasmogens. The actions of HME on gastrointestinal transit was assessed in vivo using normal defaecation and charcoal meal transit time tests in rodents. The actions of HME on gastric ulcers produced by ethanol and indomethacin were investigated. The HME was also subjected to phytochemical analysis and acute toxicity tests. Results: The HME suppressed contractions of isolated rabbit jejunum and guinea pig ileum elicited by histamine and acetylcholine. The extract elicited significant (P<0.05) reduction of normal defaecation (12.50 - 100%) and gastrointestinal propulsion of charcoal meal in mice (17.60 - 43.08%). Additionally, the extract significantly (P<0.05) prevented both ethanol- and indomethacin-induced stomach ulcers. An oral LD50 >5000 mg/kg in mice was obtained by an acute toxicity assay on HME. Conclusion: The findings showed that the leaf of H. madagascariensis has gastroprotective, antispasmodic, and antimotility properties. Keywords:Charcoal meal test, Gastric lesions, Gastrointestinal motility, Guinea pig ileum, Rabbit jejunum, Tyrode solutionView:PDF (875.22 KB)

Anti-diarrhoeal effects of Garcinia kola (Heckel-Holl) seed methanolic extract and its fractions in animal models

This study investigated the In vitro spasmolytic and In vivo anti-diarrhoeal effects of Garcinia kola seed extract/fractions. Extraction was done by maceration in 70% methanol, serially partitioned in ethyl acetate and n-hexane. Qualitative phytochemical screening was carried out on the crude extract/fractions. The In vitro spasmolytic effect of the extract and fractions at different concentrations (0.5×103, 0.2×103,0.1×103, 0.6×102 mg/ml) were investigated against spontaneous and acetylcholine-induced contractions in isolated rabbit jejunum as well as histamine-induced contractions using isolated guinea pig ileum. The In vivo anti-diarrhoeal effect of the extract was evaluated using three diarrhoeal models: castor oil-induced diarrhoea, charcoal meal gastrointestinal transit time and castor oil-induced enteropooling. In each model, 25 mice were randomly divided into five groups of 5 mice each. Group I served as the untreated control, while group II was a positive control. Groups III-V were administered 125, 250 and 500 mg/kg of the crude methanol extract, respectively. The crude extract, ethyl acetate and aqueous fractions at 0.5×103 mg/ml respectively exhibited 14.4%, 12.9% and 12.2% spasmolytic activities against acetylcholine-induced rabbit jejunum contractions. Histamine-induced guinea pig ileum contractions were inhibited by crude extract (6.2%), ethyl acetate (6.2%), aqueous fraction (7.2%) at 0.6×102 mg/ml. For castor oil-induced diarrhoea, the crude extract at 500 mg/kg produced a significant (p &lt; 0.05) decrease in the diarrhoeal index and faecal weight with a percentage inhibition of 70.4% compared with controls. Similarly, the crude extract (500 mg/kg) significantly (p &lt; 0.05) decreased the charcoal meal gastrointestinal transit time with a percentage inhibition of 33.9% and elicited significant (p &lt; 0.05) intraluminal fluid reduction (9.1%) in castor oil-induced enter pooling test when compared with the untreated group. In conclusion, the anti-motility and anti-secretory activities of the crude extract were attributed to the phytochemical constituents present.

Isolation of 1-(3',4'-Dihydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)-propan-2-ol from Grape Seed Extract and Evaluation of its Antioxidant and Antispasmodic Potential.

HPLC profiling of phenolics in grape seed extracts revealed a prominent peak of an unknown substance with concentrations up to 5.3%. Spectroscopic data allowed the identification of the compound 1 as 1-(3′,4′-dihydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)-propan-2-ol. 1 is known to be produced from catechin and epicatechin through anaerobic bacteria from human, as well as the rat, intestines. It was hypothesized that the marc remaining after expression of juice from grapes became infested during storage, resulting in the production of 1. Because compound 1 is infrequently found in nature and has never been found in grape seeds, its presence may be considered a marker of an unwanted anaerobic bacterial process occurring during production. The antioxidant potential of 1 was determined by DPPH, ABTS, and FRAP (ferric reducing antioxidant power) assays and compared to the potential of the following compounds: phloroglucine, pyrogallol, gallic acid, catechin, and epicatechin. Furthermore, it was established that 1 significantly reduced guinea pig ileum contraction induced by histamine.

Entering the spotlight: Chitosan oligosaccharides as novel activators of CaCCs/TMEM16A

Calcium-activated chloride channels (CaCCs)/TMEM16A control diverse fundamental physiological functions, and abnormal function of TMEM16A will lead to various diseases including asthma, hypertension, gastrointestinal hypomotility and cancers. Therefore, TMEM16A as drug targets for related diseases has been increasingly concerned by researchers. In this work, COS were reported as novel natural activators of TMEM16A. It was demonstrated that COS can activate TMEM16A in a concentration dependent manner, with an EC50 of 74.5 μg/mL. Then, fluorescence experiments and inside-out patch clamp experiments were combined to confirm that COS can directly activate TMEM16A. Further, we compared the activation effects of COS monomers DP2 to DP6, with DP3 the best activator. Molecular simulation was performed to find that the binding sites between DP3 and TMEM16A are E143 and E146 in TMEM16A, and it was speculated that COS and TMEM16A may be combined by electrostatic interaction. Finally, we verified that guinea pig ileum contraction was promoted by COS and the monomers through activating TMEM16A. Collectively, COS are novel efficient natural activators of TMEM16A, with potential to be developed to treatment diseases caused by down-regulation of TMEM16A including gastrointestinal hypomotility.

SPASMOLYTIC, ANTI-INFLAMMATORY, AND ANTIOXIDANT ACTIVITY OF SALVIA GESNERIFLORA LINDLEY

Background: Salvia gesneriflora Lindley is employed in traditional Mexican medicine for the treatment&#x0D; of several diseases.&#x0D; Materials and Methods: The chromatographic profile of three extracts (SgH, SgD and SgM) of this&#x0D; plant allowed the identification of 11 components in SgH, the presence of rosmarinic (1), chlorogenic (2)&#x0D; and caffeic (3) acids and quercetin glucoside (4) in SgM and of ursolic acid (5) in SgD. The spasmolytic&#x0D; (electrically induced contractions of guinea-pig ileum), anti-inflammatory (edema in mouse ear) and&#x0D; antioxidant potential (DPPH, ABTS and FRAP assays) of the extracts were evaluated.&#x0D; Results: SgM showed the highest percentage of relaxation (80.67 ± 1.633%) with no significant&#x0D; difference (p

Evidence Supports Tradition: The in Vitro Effects of Roman Chamomile on Smooth Muscles.

The dried flowers of Chamaemelum nobile (L.) All. have been used in traditional medicine for different conditions related to the spasm of the gastrointestinal system. However, there have been no experimental studies to support the smooth muscle relaxant effect of this plant. The aim of our research was to assess the effects of the hydroethanolic extract of Roman chamomile, its fractions, four of its flavonoids (apigenin, luteolin, hispidulin, and eupafolin), and its essential oil on smooth muscles. The phytochemical compositions of the extract and its fractions were characterized and quantified by HPLC-DAD, the essential oil was characterized by GC and GC-MS. Neuronally mediated and smooth muscle effects were tested in isolated organ bath experiments on guinea pig, rat, and human smooth muscle preparations. The crude herbal extract induced an immediate, moderate, and transient contraction of guinea pig ileum via the activation of cholinergic neurons of the gut wall. Purinoceptor and serotonin receptor antagonists did not influence this effect. The more sustained relaxant effect of the extract, measured after pre-contraction of the preparations, was remarkable and was not affected by an adrenergic beta receptor antagonist. The smooth muscle-relaxant activity was found to be associated with the flavonoid content of the fractions. The essential oil showed only the relaxant effect, but no contracting activity. The smooth muscle-relaxant effect was also detected on rat gastrointestinal tissues, as well as on strip preparations of human small intestine. These results suggest that Roman chamomile extract has a direct and prolonged smooth muscle-relaxant effect on guinea pig ileum which is related to its flavonoid content. In some preparations, a transient stimulation of enteric cholinergic motoneurons was also detected. The essential oil also had a remarkable smooth muscle relaxant effect in this setting. Similar relaxant effects were also detected on other visceral preparations, including human jejunum. This is the first report on the activity of Roman chamomile on smooth muscles that may reassure the rationale of the traditional use of this plant in spasmodic gastrointestinal disorders.

Corilagin Attenuates Allergy and Anaphylactic Reaction by Inhibiting Degranulation of Mast Cells.

BackgroundThis study evaluated the anti-allergic activity of corilagin and also postulates the possible mechanism of its action.Material/MethodsCorilagin was given orally at dose of 10, 20, and 40 mg/kg/day. All the animals (guinea pigs, rats, and mice) were sensitized for allergy such as eosinophilia and leukocytosis induced by milk; degranulation of mast cell by compound 48/80; and passive and active anaphylaxis. Moreover, the antagonistic effect was determined by estimating the effect of corilagin on contraction of guinea pig tracheal chain and ileum induced by Ach and histamine, respectively.ResultThere was a significant decrease in the leukocyte and eosinophil counts in the corilagin-treated group compared to the negative control group. Treatment with corilagin significantly protects the degranulation of mast cells, and it also has significant anti-muscarinic and antihistaminic activity by reducing the muscle contraction induced by Acetylcholine (Ach) and histamine in guinea pig tracheal chain and ileum.ConclusionsCorilagin possess anti-anaphylactic and anti-allergic activity by inhibiting the release of mediators from mast cells and by decreasing the serum concentration of immunoglobulin E (IgE).

Homoisoflavonoids and Chalcones Isolated from Haematoxylum campechianum L., with Spasmolytic Activity.

Haematoxylum campechianum is a medicinal plant employed as an astringent to purify the blood and to treat stomach problems such as diarrhea and dysentery. A bio-guided chemical fractionation of the methanolic extract obtained from this plant allowed for the isolation of five compounds: two chalcones known as sappanchalcone (1); 3-deoxysappanchalcone (2); three homoisoflavonoids known as hematoxylol A (3); 4-O-methylhematoxylol (4); and, hematoxin (5). The spasmolytic activity was determined in an in vitro model (electrically induced contractions of guinea pig ileum), and allowed to demonstrate that the methanolic extract (EC50 = 62.11 ± 3.23) fractions HcF7 (EC50 = 61.75 ± 3.55) and HcF9 (EC50 = 125.5 ± 10.65) and compounds 1 (EC50 = 16.06 ± 2.15) and 2 (EC50 = 25.37 ± 3.47) of Haematoxylum campechianum present significant relaxing activity as compared to papaverine (EC50 = 20.08 ± 2.0) as a positive control.

A controlled study to investigate anti-diarrhoeal effect of the stem-bark fractions of Terminalia avicennioides in laboratory animal models

Due to the shortcomings associated with modern synthetic antidiarrhoeal drugs, it is important to find newer, safer and cheaper antidiarrhoeal agents from natural sources. The study was conducted to evaluate the anti-diarrhoeal activity of the fractions of the stem-bark of Terminalia avicennioides in laboratory animal models. The effect of different concentrations (1.0×10−3, 2.0×10−3, 4.0×10−3 and 8.0×10−3mg/mL) of the aqueous methanol (AMF), ethyl acetate (EAF) and hexane (HXF) fractions of T. avicennioides were tested against spontaneous and acetylcholine-induced contractions of rabbit jejunum as well as on histamine-induced contraction of guinea pig ileum. Similarly, the effects of the AMF on gastro-intestinal transit time, castor oil-induced diarrhoea and castor oil-induced enteropooling were evaluated. The AMF, EAF and HXF at concentrations of 1.0×10−3, 2.0×10−3, 4.0×10−3 and 8.0×10−3mg/mL attenuated the contractile effects of both the spontaneous and acetylcholine-induced contractions of rabbit jejunum and that of histamine-induced contraction of guinea pig ileum in a concentration-dependent manner. The AMF at doses of 200, 300 and 500mg/kg produced significant (p<0.05) reductions in gastrointestinal transit time of charcoal and incidence of castor oil-induced diarrhoea in mice relative to the untreated control. Similarly, at doses of 300 and 500mg/kg, AMF significantly (p<0.05) reduced the weight and volume of intestinal fluid in the treated mice when compared to the untreated animals. The results of this study showed that the stem-bark of T. avicennioides possesses spasmolytic effect and could be a potential antidiarrhoeal agent. However, detailed pharmacological trials are required to justify the clinical use of the plant for treating diarrhoea.

Ginsenoside Rb1, a novel activator of the TMEM16A chloride channel, augments the contraction of guinea pig ileum.

Calcium-activated chloride channels (CaCCs) play important roles in many physiological processes, and the molecular basis of CaCCs has been identified as TMEM16A in many cell types. It is well established that TMEM16A is a drug target in many diseases, including cystic fibrosis, hypertension, asthma, and various tumors. Therefore, identifying potent and specific modulators of the TMEM16A channel is crucial. In this study, we identified the first natural activator of TMEM16A from traditional Chinese medicine and explored its mechanism. Our data showed that Ginsenoside Rb1 (GRb1) can activate TMEM16A directly from the intracellular side in a dose-dependent manner at an EC50 of 38.4±2.14μM. GRb1 specifically activated TMEM16A/B, but not the other previously proposed CaCC mediators such as CFTR and bestrophin. Moreover, GRb1 promoted proliferation of CHO cells stably expressing TMEM16A, in a concentration-dependent manner. Finally, we showed that GRb1 increased the amplitude and frequency of contractions in an isolated guinea pig ileum assay in vivo. In summary, GRb1 can be considered a lead compound for the development of novel drugs for the treatment of diseases caused by TMEM16A dysfunction.

Differential effects of R-isovaline and the GABAB agonist, baclofen, in the guinea pig ileum

R-isovaline is a non-proteinogenic amino acid which produces analgesia in a range of nociceptive assays. Mediation of this effect by metabotropic receptors for γ-aminobutyric acid (GABA) and glutamate, demonstrated by previous work, may depend on the type of tissue or receptor system. The objective of this study was to assess the activity of R-isovaline acting at GABAB and group II metabotropic glutamate receptors in guinea pig ileum, which is known to exhibit well-defined responses to GABAB agonists such as baclofen. The effects of bath-applied R-isovaline and RS-baclofen were examined on electrically evoked contractions of guinea pig ileum and during GABAB antagonism by CGP52432. In separate experiments, the group II metabotropic glutamate receptor agonist, LY354740 was applied to determine the functional presence of these receptors. R-isovaline (1–100mM) decreased the amplitude of ileal muscle contractions and increased tension. RS-baclofen reduced contraction amplitude, but decreased tension. CGP52432 did not prevent the effects of R-isovaline on contraction amplitude, but antagonized effects of RS-baclofen on contraction amplitude. The group II metabotropic glutamate receptor agonist, LY354740, produced no detectable effects on evoked contractions. R-isovaline differed significantly from RS-baclofen in its actions in the guinea pig ileum, indicated in particular by the finding that CGP52432 blocked only the effects of RS-baclofen. The ileal tissue did not respond to a group II metabotropic glutamate receptor agonist, previously shown to co-mediate R-isovaline analgesia. These findings raise the possibility of a novel therapeutic target at unknown receptors for R-isovaline-like compounds in the guinea pig ileum.

Antiemetic activity of effective extract and bioactive compounds in ginger

To investigate the antiemetic effect of the active extract (ginger ether extract, GEE) and its bioactive compounds in ginger, the pica vomiting model in rats and the gastric emptying model in mice were used to observe the antiemetic effect of GEE in cisplatin-induced pica and gastric emptying, and the main components in GEE were detected by RP-HPLC; in vitro, the antagonist effect of GEE and the four components in it were explored by the contraction of guinea-pig ileum induced by SR57227A and carbachol. The results showed that the amount of Kaolin ingested by rats were declined significantly in all the three groups of GEE (25,50,100 mg•kg⁻¹) (P<0.01), while cisplatin-induced gastric emptying in mice was also suppressed in all the three groups (P<0.01), and 6-gingerol, 8-gingerol,10-gingerol and 6-shogaol were found mainly in GEE by RP-HPLC; the maximum contraction of isolated guinea-pig ileum could be reduced by addition of GEE (2.3, 4.6, 11.5 mg•L⁻¹), 6-gingerol,8-gingerol,10-gingerol or 6-shogaol (1, 2, 5 μmol•L⁻¹) when the concentration of SR5727A was 1×10⁻⁵ mol•L⁻¹ and that of carbachol was 1×10⁻⁴ mol•L⁻¹ (P<0.05, P<0.01). In conclusion, 5-HT3 and M3 receptors could be antagonized by GEE and its bioactive compounds 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol, which may be correlated with the antiemetic mechanism of ginger maybe related to it.

Flavonoid galetin 3,6-dimethyl ether attenuates guinea pig ileum contraction through K+ channel activation and decrease in cytosolic calcium concentration

Flavonoid galetin 3,6-dimethyl ether (FGAL) has been isolated from the aerial parts of Piptadenia stipulaceae and has shown a spasmolytic effect in guinea pig ileum. Thus, we aimed to characterize its relaxant mechanism of action. FGAL exhibited a higher relaxant effect on ileum pre-contracted by histamine (EC50=1.9±0.4×10−7M) than by KCl (EC50=2.6±0.5×10−6M) or carbachol (EC50=1.8±0.4×10−6M). The flavonoid inhibited the cumulative contractions to histamine, as well as to CaCl2 in depolarizing medium nominally Ca2+-free. The flavonoid relaxed the ileum pre-contracted by S-(–)-Bay K8644 (EC50=9.5±1.9×10−6M) but less potently pre-contracted by KCl or histamine. CsCl attenuated the relaxant effect of FGAL (EC50=1.1±0.3×10−6M), but apamin or tetraethylammonium (1mM) had no effect (EC50=2.6±0.2×10−7 and 1.6±0.3×10−7M, respectively), ruling out the involvement of small and big conductance Ca2+-activated K+ channels (SKCa and BKCa, respectively). Either 4-aminopyridine or glibenclamide attenuated the relaxant effect of FGAL (EC50=1.8±0.2×10−6 and 1.5±0.5×10−6M, respectively), indicating the involvement of voltage- and ATP-sensitive K+ channels (KV and KATP, respectively). FGAL did not alter the viability of intestinal myocytes in the MTT assay and decreased (88%) Fluo-4 fluorescence, indicating a decrease in cytosolic Ca2+ concentration. Therefore, the relaxant mechanism of FGAL involves pseudo-irreversible noncompetitive antagonism of histaminergic receptors, KV and KATP activation and blockade of CaV1, thus leading to a reduction in cytosolic Ca2+ levels.

Pharmacological evaluation of a polyherbal formulation for its antispasmodic activity

Object: The present study was aimed to evaluate pharmacologically to a polyherbal formulation containing volatile extracts of various umbelliferae plants. Materials and Methods: The umbelliferae family was found most effective against spasm by extensive literature review and study of various rational formulations. Plants material was procured from the local market of Rajasthan. Volatile extracts were isolated from powdered plant materials through Clevenger’s method. The volatile extracts of following plants Trachyspermum ammi, Cuminum cyminum, Anethum graveolens and Foeniculum vulgare were used to make polyherbal formulation. Results: Antispasmodic effect of newly prepared polyherbal formulation demonstrated on guinea pig ileum in vitro; 50% inhibitory concentration (IC50) was 172.5 ± 1.4 μl/ml. A very effective value identified, when compared to antispasmodic drugs, e.g. Atropine (IC50 was 166.7 ± 1.2 μl/ml). Oral administration of polyherbal formulation dose‐dependently reduced intestinal transit in mice when compared to atropine at 0.1 mg/kg i.p. and formulation at (300 mg/kg) protected mice against diarrhea induced by castor oil significantly when compared to control and standard loperamide at a dose of 5 mg/kg orally. Conclusion: Polyherbal formulation inhibits acetylcholine and calcium chloride induced contraction of guinea pig ileum dose‐dependently. The current research validates antispasmodic effect of newly developed polyherbal formulation. It also concluded that polyherbal formulation inhibits the contraction produced by various spasmogens like acetylcholine and calcium chloride. This suggests that the activity of developed formulation is nonspecific to any spasmogen. Key words: Antispasmodic, atropine, guinea pig ileum, a polyherbal formulation.

Pharmacological properties of the repellent secretion of &lt;i&gt;Zonocerus variegatus&lt;/i&gt; (Orthoptera: Prygomorphidae)

The odours of the whole body and the secretion of Zonocerus variegatus were easily recognised and perceived by human volunteers. However, the secretion odour is not related to the odour of the food plant consumed by the grasshopper. The repellency of Z. variegatus becomes more pronounced in the 6th. and adult instars whose gland lumens contain an appreciable volume of secretion. The secretion odour is so strong that even dilution does not affect its repulsiveness to humans. The secretion had pharmacological properties: it induced contraction in rat (Rattus rattus) stomach smooth muscle preparations and guinea pig (Cavia porcellus) ileum, and induced oedema formation in the rat hind paw. The secretion was not lethal to the animals used in this study, effects were temporary and recovery occurs after a short time.

Evaluation of bronchodilatory properties of fruits of Opuntia elatior Mill

Background Traditionally, fruits of Opuntia elatior Mill. were used for their immunomodulatory and antiasthmatic action. The presence of potentially active nutrients and their multifunctional properties make prickly pear a perfect candidate for the production of phytopharmaceutical products. Objective The objective of the present study was to evaluate the bronchodilatory properties of fruits of O. elatior Mill. Materials and methods The bronchodilatory properties were evaluated using bronchospasm induced by acetylcholine and histamine, anticholinergic action on isolated rat ileum, and antihistaminic action on isolated guinea pig ileum. Result and discussion Bronchodilating effect of fruit juice was dose dependent against spasm induced by acetylcholine and histamine. O. elatior Mill. fruits possess a significant inhibitory effect on rat and guinea pig ileum contraction through antihistaminic and antimuscarinic action. Conclusion This study suggested that fruits of O. elatior Mill. possess a significant inhibitory effect on rat and guinea pig ileum, and betacyanin, an active principle compound in prickly pear, may be responsible for the action.

Inhibition of native 5-HT3 receptor-evoked contractions in guinea pig and mouse ileum by antimalarial drugs

Quinine, chloroquine and mefloquine are commonly used to treat malaria, however, with associated gastrointestinal (GI) side-effects. These drugs act as antagonists at recombinant 5-HT3 receptors and modulate gut peristalsis. These gastrointestinal side effects may be the result of antagonism at intestinal 5-HT3 receptors. Ileum from male C57BL/6 mice and guinea pigs was mounted longitudinally in organ baths. The concentration–response curves for 5-HT and the selective 5-HT3 agonist 2-Me-5-HT were obtained with 5-HT (pEC50=7.57±0.33, 12) more potent (P=0.004) than 2-Me-5-HT (pEC50=5.45±0.58, n=5) in mouse ileum. There was no difference in potency of 5-HT (pEC50=5.42±0.15, n=8) and 2-Me-5-HT (pIC50=5.01±0.55, n=11) in guinea pig ileum (P>0.05). Quinine, chloroquine or mefloquine was applied for 10min and inhibitions prior to submaximal agonist application. In mouse ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions (pIC50=4.9±0.17, n=7; 4.76±0.14, n=5; 6.21±0.2, n=4, correspondingly) with mefloquine most potent (P<0.05). Quinine, chloroquine and mefloquine antagonised 2-me-5-HT-induced contractions (pIC50=6.35±0.11, n=8; 4.64±0.2, n=7; 5.11±0.22, n=6, correspondingly) with quinine most potent (P<0.05). In guinea-pig ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions (pIC50=5.02±0.15, n=6; 4.54±0.1, n=7; 5.32±0.13, n=5) and 2-me-5-HT-induced contractions (pIC50=4.62±0.25, n=5; 4.56±0.14, n=6; 5.67±0.12, n=4) with chloroquine least potent against 5-HT and mefloquine most potent against 2-me-5-HT (P<0.05). These results support previous studies identifying anti-malarial drugs as antagonists at recombinant 5-HT3 receptors and may also demonstrate the ability of these drugs to influence native 5-HT3 receptor-evoked contractile responses which may account for their associated GI side-effects.

Orally active opioid μ/δ dual agonist MGM-16, a derivative of the indole alkaloid mitragynine, exhibits potent antiallodynic effect on neuropathic pain in mice.

(E)-Methyl 2-((2S,3S,7aS,12bS)-3-ethyl-7a-hydroxy-8-methoxy-1,2,3,4,6,7,7a,12b-octahydroindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate (7-hydroxymitragynine), a main active constituent of the traditional herbal medicine Mitragyna speciosa, is an indole alkaloid that is structurally different from morphine. 7-Hydroxymitragynine induces a potent antinociceptive effect on mouse acute pain through μ-opioid receptors. In this study, we developed dual-acting μ- and δ-opioid agonists MGM-15 and MGM-16 from 7-hydroxymitragynine for the treatment of acute and chronic pain. MGM-16 showed a higher potency than that of 7-hydroxymitragynine and MGM-15 in in vitro and in vivo assays. MGM-16 exhibited a high affinity for μ- and δ-opioid receptors, with K(i) values of 2.1 and 7.0 nM, respectively. MGM-16 showed μ- and δ-opioid full agonistic effects in a guanosine 5'-O-(3-[(35)S]thiotriphosphate) binding assay and in a functional test using electrically elicited guinea pig ileum and mouse vas deferens contractions. Systemic administration of MGM-16 produced antinociceptive effects in a mouse acute pain model and antiallodynic effects in a chronic pain model. The antinociceptive effect of MGM-16 was approximately 240 times more potent than that of morphine in a mouse tail-flick test, and its antiallodynic effect was approximately 100 times more potent than that of gabapentin in partial sciatic nerve-ligated mice, especially with oral administration. The antinociceptive effect of MGM-16 was completely and partially blocked by the μ-selective antagonist β-funaltrexamine hydrochloride (β-FNA) and by the δ-selective antagonist naltrindole, respectively, in a tail-flick test. The antiallodynic effect of MGM-16 was completely blocked by β-FNA and naltrindole in a neuropathic pain model. These findings suggest that MGM-16 could become a class of a compound with potential therapeutic utility for treating neuropathic pain.

Antiallergic Effects of Pigments Isolated from Green Sea Urchin (Strongylocentrotus droebachiensis) Shells

This study was undertaken to evaluate possible antiallergic effects of an extract of pigments from green sea urchin (Strongylocentrotus droebachiensis) shells. Effects were studied on animal models - guinea pig ileum contraction, rabbit eyes allergic conjunctivitis, and rabbit local skin irritation. The extract significantly reduced, in a dose-dependent manner, the histamine-induced contractions of the isolated guinea pig ileum with ID50 =1.2 µg/mL (in equivalents of spinochrome B), had an inhibitory effect on the model of ocular allergic inflammation surpassing the reference drug olopatadine, and did not show any irritating effect in rabbits. The extract predominantly contained polyhydroxy-1,4-naphthoquinone which would be responsible for the pharmacological activity. The active compounds of the extract were evaluated in silico with molecular docking. Molecular docking into H1R receptor structures obtained from molecular dynamic simulations showed that all spinochrome derivatives bind to the receptor active site, but spinochrome monomers fit better to it. The results of the present study suggest possibilities for the development of new agents for treating allergic diseases on the base of pigments from sea urchins shells.

Antihistaminic evaluation of formulated polyherbal cough syrup

Allergic rhinitis is one of the most common allergic disorders throughout the world. The conventional therapies are effective in alleviating symptoms but the efficacy is limited and not persistent. Many of the indigenous herbal preparations used by the tribes are little known to the public due to lack of scientific evaluation. The aqueous ethanol extracts of various traditional herbs like Adhatoda vasica, Acorus calamus, Glyzyrrhiza glabra, Ocimum sanctum, Tylophora asthmatica, Piper longum and Solanum xanthocarpum was evaluated for its antihistaminic activity by the inhibition of histamine induced contractions on the guinea pig ileum. The results showed that the formulated cough syrup inhibited histamine induced contractions of guinea pig ileum at 2.5 to 25 µg/ml concentrations in a dose dependent manner (p < 0.01, p < 0.05) and also significantly (p < 0.05) inhibited degranulation of mast cells. All the results were well comparable with the standard benadryl cough syrup (diphenhydramine). Key words: Antihistaminic syrup, formulation, asthma, siddha, ayurveda.