Antihistaminic activity of Ethanolic extract of Capparis moonii W. fruit.

The purpose of the present work were intended to determine the antihistaminic activity of ethanolic extract of Capparis moonii W. fruits (EECM). Capparis moonii W. had been historically used in the diagnosis of cough and asthma and so we undertook this study to validate scientifically using appropriate animal models. Antihistamine is considered to be helpful for the treatment of allergic, thus, the antihistamine activity of an ethanolic extract of Capparis moonii W. in the current work was evaluated. To determine the doses, acute oral toxicity tests were conducted. Clonidine and haloperidol that induced cataleptic effect in Swiss albino mice were evaluated for antihistaminic activity at the different doses of 50mg/kg, 100mg/kg and 200mg/kg, p.o. and the evaluation is also done on guinea pig ileum tissue. The ethanolic extract of Capparis moonii W. fruits (50, 100, 200mg/kg, p.o.) and chlorpheniramine maleate (i.p.,10mg/kg) significantly inhibited (****P<0.0001) clonidine induced catalepsy but the extract donot inhibit haloperidol-induced catalepsy and histamine-induced contraction in guinea pig ileum tissue preparation shows that ethanolic extract of Capparis moonii W. inhibited the contractile activity of histamine. The result of our work shows that the ethanolic extract possesses antihistaminic activity. It can be reported that flavonoid present in the extract may be important for an antihistaminic effect and therefore may have a role in the asthma treatment.

Antidiarrhoeal potentials of methanol bark extract of Hymenocardia Acida Tul (Euphorbiaceae) in laboratory animals

Background The plant Hymenocardia acida (Euphorbiaceae) is utilized as herbal preparation against diarrhoea, dysentery and other diseases. We aimed to determine the antidiarrhoeal potentials of Hymenocardia acida (MEHA) stem bark in vivo and in vitro. Preliminary phytochemical contents, as well as the acute toxicity effect of the extract, were investigated based on standard experimental methods. The antidiarrhoeal properties of the MEHA at 150, 300 and 600 mg/kg were studied against diarrhoea induced by castor oil, intestinal fluid accumulation, as well as intestinal movement tests using distilled water (10 ml/kg) and loperamide/atropine sulphate as the control groups. Besides, the in vitro effects of the extract (8 × 10−2–640 × 10−2 mg/ml) on the rabbit jejunum and guinea-pig ileum were evaluated. Results Phytochemical screening showed alkaloids, glycoside, saponins, tannins, triterpenes, flavonoids and steroids in the MEHA. The median lethal dose (LD50) of the MEHA after oral administration was approximately greater than 2000 mg/kg. The MEHA declined the diarrhoea onset and remarkably decreased the number of watery stools in the group that received 300 and 600 mg/kg. It also elicited a remarkable and non-dose-dependent reduction in the intestinal fluid volume. At 1000 mg/kg, the MEHA significantly inhibited the charcoal movement. In addition, the MEHA (8 × 10−2–640 × 10−2 mg/ml) elicited a remarkable decrease in the contractility of the rabbit jejunum over time and relaxed the guinea pig ileum. Besides, it showed concentration-dependent attenuation of the acetylcholine and histamine-induced contraction. Conclusion The extract under investigation revealed promising antidiarrhoeal properties that justified its traditional claim for use against diarrhoea.

LUEM PUA RICE EXTRACT ATTENUATES THE SEVERITY OF DEXTRAN SULFATE SODIUMINDUCED ULCERATIVE COLITIS IN RATS THROUGH CHOLINOMIMETIC EFFECTS

Objective: The objective of the study was to investigate the effect of aqueous extract of unpolished dark purple glutinous Thai rice variety Luem Pua(LP) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in rat and the possible cholinomimetic effects of the extract.Methods: The effect of LP extract (0.5, 1, or 1.5 mg/ml final concentration) on ileum contraction was tested using isolated guinea pig ileum. Certainagonists (acetylcholine, tetramethylammonium, and clonidine) and antagonists (hexamethonium chloride and atropine) were studied to determinethe cholinomimetic effect of the extract. The effects of LP extract (5 g/kg/day) in DSS-induced UC model (drinking water was replaced with 3%DSS in water for 7 days) in rat were evaluated. On each day of treatment, the change of disease activity index (DAI) was recorded. At the end of theexperiments, rats were terminated and disease severity expressed as DAI, colon length, and spleen weight were determined.Results: LP extract at the concentration of 0.5, 1, and 1.5 mg/ml (final concentration) could contract the ileum in a dose-dependent manner and beblocked completely by atropine. Oral administration of LP extract could significantly attenuate the severity of DSS-induced UC as seen by the reductionof DAI, colon length, and spleen weight.Conclusion: Results in isolated guinea pig ileum suggest that LP might contain active substance that could activate muscarinic receptors. In additionto antioxidant activity, through activation of muscarinic receptor, might explain the protective effects of LP extract against DSS-induced UC in rats.

Oceanapia magna Sponge Presents Dual Effect on the Gastrointestinal Motility of Rodents: In Vitro and In Vivo Assays

Oceanapia magna Santos-Neto, Nascimento, Cavalcanti and Pinheiro sponges are distributed across tropical worldwide seas. Some studies of marine products have shown interesting activities in smooth muscle models. Hence, we assessed the effect of the ethanolic extract of Oceanapia magna. (OC-EtOH) on acute toxicity and gastrointestinal motility (in vitro and in vivo) in rodent models. On guinea pig ileum, OC-EtOH induced a concentration dependent contraction on basal tonus, which was not inhibited by atropine, but in the presence of pyrilamine or verapamil, the effect was antagonized. Contrastingly, on KCl- or histamine-induced contractions, OC-EtOH presented a transient contraction followed by a concentration-dependent relaxation. Moreover, OC-EtOH presented a relaxant profile on cumulative curves to CaCl2 and tonic contraction induced by S-(-)-BayK8644, through Cav blockade. The acute toxicity assay showed that OC-EtOH (2,000 mg/kg, p.o.) did not present any sign of toxicity in female mice. Additionally, OC-EtOH presented antidiarrheal effect in mice, increased the intestinal normal transit and reduced the castor oil-induced intestinal transit. Thus, OC-EtOH presented a dual effect on guinea pig ileum promoting contraction through activation of H1 and CaV, and relaxation through CaV blockade, besides the effect on upper gastrointestinal transit in mice, showing a potential medicinal use of this sponge in intestinal diseases such as diarrhea.

Study of Antispasmodic and Antidiarrheal Activities of Tagetes lucida (Mexican Tarragon) in Experimental Models and Its Mechanism of Action

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

Diterpenoids from Leaves of Cultivated Plectranthus ornatus

Two new diterpenoid derivatives 7α,12β,17-triacetoxy-6β,19-dihydroxy-13β,16-spirocicloabiet-8-ene-11,14-dione (1) and 6β-acetoxy-3β,7α,12α-trihydroxy-13β,16-spirocicloabiet-8-ene-11,14-dione (2) along with 11 (3–13) miscellaneous compounds were isolated from the leaves of Plectranthus ornatus Codd. Their structures were elucidated by spectroscopic analysis and gauge independent atomic orbitals 13C NMR calculations. The isolated compounds were screened for their effects on intestinal motility using guinea-pig ileum and duodenum and by their cytotoxicity against 4 human cancer cell lines (HCT-116, SF-295, PC-3, and HL-60). Compounds 6 and 9 were moderately cytotoxic against HL-60, whereas 6 and 13 were more active on SF-295 and HCT-116.

In sillico analysis, synthesis, and biological evaluation of triazole derivatives as a H1 receptor antagonist

Background: Histamine, a biological amine, is considered as a principal mediator of many pathological processes regulating several essential events in allergies and autoimmune diseases. Numerous derivatives have been developed that strive with histamine at H1 receptor and prevent binding of histamine at H1 receptor thus prevent allergic reactions. Molecules containing triazole ring fused with six-membered ring systems are found to possess broad applications in the field of medicine and industry. The present study is an attempt to characterize the impact of the nature of the substituent introduced at the 5 positions of the-4H-1,2,4-triazole-3-thiol on their capacities to bind with H1 receptor. Methods: Molecular docking (PDB ID: 3RZE) revealed that synthesized derivatives and target proteins were actively involved in binding with Tyr-108, Thr-112, Ala-216, and Phe432 subunits. The pharmacophore model new 5-(4-substituted phenyl)-4-(phenylamino)- 4-H-1,2,4-triazole-3-thiols (5a-5h) were designed and evaluated for H1-blocking activity using isolated segments from the guinea pig ileum. Results: According to in silico analysis, all the compounds have a topological polar surface area (TPSA) less than 140 Å squared, so they tend to a good penetration in cell membranes. The results show that most of the compounds are non-inhibitors of CYP450 substrates that play a fundamental role in drug metabolism. Compounds 5d (50.53±12.03), 5h (50.62±12.33) and 7a (55.07±12.41) are more active than others. Conclusion: Finally, these derivatives were screened for H1 receptor antagonist activity using guinea pig ileum taking chlorpheniramine maleate as a standard. Most of the compounds possesses better antihistamine activity.

Amphibian toxins from the skin of Bufo regularis have inhibitory effect on electrically invoked contractile response and bimodal effects on tone of longitudinal muscle of guinea pig ileum

The skins of some amphibians contain potentially bioactive principles that may have pharmaceutical, medicinal, toxicological or chemical importance. In addition, such active principles can be used as tools in biomedical research. The present study aims at isolating and purifying bioactive principles from the skin of Bufo regularis and studying their effect on isolated longitudinal smooth muscle strip of guinea pig ileum. High performance liquid chromatography (HPLC) was used to isolate toad toxins. The effects of crude, semi-purified and purified extracts were tested on longitudinal smooth muscle of guinea pig ileum using organ bath method. Effect of the toxins was studied on electrically-induced contractile response and the basal tone of the longitudinal muscle strip. HPLC purification resulted in four different bioactive components with a λmax UV absorbance pattern of around 295 nm. When tested on guinea pig ileum they had persistent inhibitory effect on the electrically-induced contractile responses. The pattern of effect was initial excitatory followed by long lasting inhibitory effect on tone of longitudinal muscle. The HPLC eluate at 79th min in methanol preparative run corresponding to the eluate at 40th min in the acetonitrile run had the maximum bioactivity. Hence, it was concluded that the skin of B. regularis contains four different components which vary in their potency on isolated smooth muscle strip of guinea pig ileum.Keywords: Bufo regularis, organ bath, longitudinal muscle of ileum, toad toxin, electrical field stimulation