Guinea Pig Ileum Research Articles

Lentil Waste Extracts for Inflammatory Bowel Disease (IBD) Symptoms Control: Anti-Inflammatory and Spasmolytic Effects

Background/Objectives: In the contest of agro-industrial waste valorization, we focused our attention on lentil seed coats as a source of health-promoting phytochemicals possibly useful in managing inflammatory bowel diseases (IBDs), usually characterized by inflammation and altered intestinal motility. Methods: Both traditional (maceration) and innovative microwave-assisted extractions were performed using green solvents, and the anti-inflammatory and spasmolytic activities of the so-obtained extracts were determined through in vitro and ex vivo assays, respectively. Results: The extract obtained through the microwave-assisted procedure using ethyl acetate as the extraction solvent (BEVa) proved to be the most useful in inflammation and intestinal motility management. In LPS-activated Caco-2 cells, BEVa down-regulated TLR4 expression, reduced iNOS expression and the pro-inflammatory cytokine IL-1 production, and upregulated the anti-inflammatory cytokine IL-10 production, thus positively affecting cell inflammatory responses. Moreover, a significant decrease in the longitudinal and circular tones of the guinea pig ileum, with a reduction of transit speed and pain at the ileum level, together with reduced transit speed, pain, and muscular tone at the colon level, was observed with BEVa. HPLC separation combined with an Orbitrap-based high-resolution mass spectrometry (HRMS) technique indicated that 7% of all the identified metabolites were endowed with proven anti-inflammatory and antispasmodic activities, among which niacinamide, apocynin, and p-coumaric acid were the most abundant. Conclusions: Our results suggest that lentil hull extract consumption could contribute to overall intestinal health maintenance, with BEVa possibly representing a dietary supplementation and a promising approach to treating intestinal barrier dysfunction.

Translational Perspectives on the Therapeutic Potential of Hyptis Crenata Essential Oil Terpenes in Smooth Muscle Function.

Monoterpenes and sesquiterpenes are classes of organic compounds found in various natural products, such as the essential oil of Hyptis crenata (EOHc). The therapeutic potential of these terpenes present in EOHc is evidenced by their effect on smooth muscle and potential clinical applications. Among the highlighted monoterpenes, such as sabinene, α-pinene, and β-pinene, a relaxing effect on rat intestinal smooth muscles is observed, attributed to interaction with calcium channels. Furthermore, monoterpenoids like borneol, cineole, and linalool also demonstrate vasorelaxant properties, suggesting potential in the treatment of cardiovascular conditions. Sesquiterpenes, such as caryophyllene and aromadendrenes, exhibit relaxing effects in various smooth muscle tissues, such as rat uterus and guinea pig ileum, indicating pharmacological potential in these areas. The translational exploration of targets, such as calcium channels and G protein-coupled receptors, highlights the importance of these compounds in discovering new therapies based on natural products for treating various medical conditions.

Unraveling the multi-faceted role of Rosmarinus officinalis L. (rosemary) and diosmetin in managing gut motility

Ethnopharmacological relevanceRosmarinus officinalis L. (Rosemary) is a popular herb with reported effectiveness against diarrhea, anxiety and constipation, albeit with limited pharmacological evidence. Aim of the studyThe current study was aimed at evaluating the therapeutic potential, possible pharmacological mechanisms of action and active constituents of hydro-ethanolic extract of rosemary (Rs.Cr), as potential anti-diarrheal, laxative and anxiolytic agent. MethodRs.Cr was analyzed through reverse-phase high pressure liquid chromatography (RP-HPLC). Laxative, antidiarrheal, and anxiolytic activities were assessed using in vivo models. Spasmogenic and spasmolytic mechanisms were studied on isolated guinea pig ileum and rabbit jejunum tissues, respectively. Possible role of diosmetin, one of the active constituents of Rs.Cr was also evaluated. ResultsRP-HPLC analysis revealed presence of diosmetin, rutin and apigenin in Rs.Cr. Laxative effect was seen at low doses, which was partially reversed in atropinized mice. The spasmogenic mechanism was mediated by cholinergic and histaminergic receptors stimulation. At higher doses, antidiarrheal activity was evident, with reduction in gastrointestinal motility and secretions using charcoal meal and enteropooling assays, respectively. Rs.Cr also showed dose-dependent anxiolytic effect. The antispasmodic mechanisms were mediated by anti-muscarinic and K+ channel opening-like effect (predominant KATP-dependent). Diosmetin exhibited antidiarrheal and antispasmodic activities, but spasmogenic effect was not seen. ConclusionRosemary leaves have dual antidiarrheal and laxative effects, and as well as anxiolytic activity. In addition, the possible modulation of muscarinic and histaminergic receptors, and KATP channels show it as potential herb to be explored for irritable bowel syndrome. Diosmetin is possibly one of its constituents that contributes to its antidiarrheal activity.

Microbiota Alterations in Lung, Ileum, and Colon of Guinea Pigs with Cough Variant Asthma.

Alterations in the microbiota composition, or ecological dysbiosis, have been implicated in the development of various diseases, including allergic diseases and asthma. Examining the relationship between microbiota alterations in the host and cough variant asthma (CVA) may facilitate the discovery of novel therapeutic strategies. To elucidate the diversity and difference of microbiota across three ecological niches, we performed 16S rDNA amplicon sequencing on lung, ileum, and colon samples. We assessed the levels of interleukin-12 (IL-12) and interleukin-13 (IL-13) in guinea pig bronchoalveolar lavage fluid using the enzyme-linked immunosorbent assay (ELISA). We applied Spearman's analytical method to evaluate the correlation between microbiota and cytokines. The results demonstrated that the relative abundance, α-diversity, and β-diversity of the microbial composition of the lung, ileum, and colon varied considerably. The ELISA results indicated a substantial increase in the level of IL-13 and a decreasing trend in the level of IL-12 in the CVA guinea pigs. The Spearman analysis identified a correlation between Mycoplasma, Faecalibaculum, and Ruminococcus and the inflammatory factors in the CVA guinea pigs. Our guinea pig model showed that core microorganisms, such as Mycoplasma in the lung, Faecalibaculum in the ileum, and Ruminococcus in the colon, may play a crucial role in the pathogenesis of CVA. The most conspicuous changes in the ecological niche were observed in the guinea pig ileum, followed by the lung, while relatively minor changes were observed in the colon. Notably, the microbial structure of the ileum niche approximated that of the colon niche. Therefore, the results of this study suggest that CVA development is closely related to the dysregulation of ileal, lung, and colon microbiota and the ensuing inflammatory changes in the lung.

Effect of Eraippu Noi Chooranam (ENC) on Histamine and Acetylcholine Induced Isolated Guinea Pig Ileum

Effect of Eraippu Noi Chooranam (ENC) on Histamine and Acetylcholine Induced Isolated Guinea Pig Ileum

Pharmacological disadvantages in the spasmolytic effects by using the mixture known as “three toronjiles” in folk medicine

Ethnopharmacology relevanceIn Mexico, Agastache mexicana subsp. mexicana (PT) and subsp. xolocotziana (WT), and Dracocephalum moldavica (BT), are used together as the “three toronjiles” to treat gastrointestinal spasms. Aim of studyTo evaluate if the spasmolytic activity of these three medicinal species is better in combination or in an individual manner. Materials and methodsSpasmolytic effect of PT, WT and BT alone or combinate were evaluated in rings of the guinea-pig ileum contracted with potassium chloride (KCl), electrical field stimulation (EFS), or acetylcholine (ACh). Chemical analysis by thin layer and ultra-high pressure liquid chromatography of the aqueous extracts of each species were done for their comparison, and their acute toxicity were determined in mice. ResultsPT and WT diminished in a dose-dependent manner the contractions induced by KCl, EFS, and ACh. Whereas BT did not altered contractions in any experimental protocol. A combination of the PT (EC50) and WT (EC50) diminished the contractions induced by KCl or EFS. Interestingly, the addition of BT extract (10 μg/ml) to the combination (PT EC30 + WT EC30) blocked the inhibitory effect produced on the contracted tissue in the presence of KCl, EFS, or ACh. Moreover, addition of BT extract (100 μg/ml) to the same combination blocked the inhibitory effect on the pre-contracted tissue only in the presence of EFS. None of the aqueous extracts produced toxicity in its individual administration in mice. Chemical analysis demonstrated similarities between PT and WT, but differences with BT. ConclusionsThe results of this study confirmed that either combined or by themselves aqueous extracts of PT and WT produced a spasmolytic action on guinea pig ileum, suggesting that this combination of medicinal plants could relieve gastrointestinal diseases in human, but when BT aqueous extract is added to those obtained with PT and WT, the spasmolytic activity diminished or even was blocked. Our results give evidence that mixture of several plants might produce disadvantages in the medicinal properties of their individual activity.

Potential role of Albizia lebbeck and Emblica officinalis on smooth muscle contractions in experimental animal models

Background and objectiveSpasms are involuntary muscular contractions commonly seen frequently. This study used isolated tissue preparations to test the efficacy of Albizia lebbeck (A.L) and Emblica officinalis (E.O) extracts for spasmolytic activity. Materials and methodsThe herbal extracts were tested in isolated guinea pig ileum, rat uterus, rat fundus, and rabbit jejunum. Histamine was used as spasmogen in guinea pig ileum, while 5-hydroxytryptamine (5-HT) was in rat uterus and rat fundus. Spontaneous contractions' amplitude and frequency were recorded in the rabbit jejunum after administering herbal extracts. The influence of the extracts on smooth muscle contraction was calculated and statistically analyzed by one-way ANOVA. The P value was kept at <0.05 for all statistical analyses to consider it significant. ResultsObservation from the present study indicated that A.L significantly (p < 0.05) enhanced the contraction induced by histamine and 5-HT in guinea pig ileum (50 mcg/ml) and rat fundus (150 mcg/ml), respectively. In the rabbit jejunum, the amplitude and frequency of contraction were significantly (p < 0.05) reduced at 500 mcg/ml. E.O. was found to suppress the spasmogenic (histamine and 5-HT) at doses beyond 150 mcg/ml and, in rabbit jejunum, enhanced the amplitude and frequency of contraction at 50 and 150 mcg/ml. The IC50 values for E.O. in guinea pig ileum, rat uterus, and rat fundus were 35.2, 50.3, and 124.7 mcg/ml, respectively. ConclusionThe observation suggests that A.L enhanced smooth muscle contraction in the presence of known spasmogens and reduced it in the absence. Opposite effects were found for E.O., where it reduced contraction in the presence of spasmogens and increased in the absence. These findings suggest potential spasmogenic/spasmolytic activities of the tested extracts.

Comparative evaluation of the potential anti-spasmodic activity of Piper longum, Piper nigrum, Terminalia bellerica, Terminalia chebula, and Zingiber officinale in experimental animals

BackgroundSpasm of muscle is one of the frequent complaints seen by most of the population worldwide. The present study evaluated the efficacy of some of the commonly used herbal extracts against known spasmogens, such as histamine and 5-hydroxytryptamine (5-HT). Material and methodsThe study was conducted on isolated guinea pig ileum and rat uterus preparations using histamine and 5-HT, respectively. Five herbal extracts such as Piper longum (P.L), Piper nigrum (P.N), Terminalia bellerica (T.B), Terminalia chebula (T.C), and Zingiber officinale (Z.O) were tested. Herbal extracts at doses 50, 150, 500, 1500, and 5000 mcg/ml were pretreated to the isolated tissue preparation, and the contractile response of histamine and 5-HT was recorded. The efficacy and the inhibitory concentration (IC50) were calculated and statistically analyzed by one-way ANOVA. ResultsThe study indicated that all five herbal extracts produced a concentration-dependent suppression of histamine and 5-HT-induced responses. A significant (p < 0.05) non-competitive antagonism was observed against the known spasmogen induced smooth muscle contraction for P.L, P.N, T.B, and Z.O in both guinea pigs and rat uterus preparation. Moreover, P.L and P.N completely abolished (100%) the contractile response induced by histamine and 5-HT. Although, T.C produced a concentration-dependent reduction in known spasmogen-induced contraction but the response was found to be statistically non-significant (p greater than 0.05). ConclusionThe finding suggested that P.L. and P.N. have better activity in terms of reducing the spasmogenic contractions compared to other extracts. Additionally, T.B. and Z.O. can lessen the uterine and intestinal contractions brought on by spasmogens. Although P.L and P.N demonstrated better efficacy against the spasmogenic activity of histamine and 5-HT, more research, particularly on isolated phytochemicals of the extracts and involving different experimental models, is required before establishing the precise safety and efficacy against spasmogenic-induced disorders.

Aqueous Extract of Malus domestica Inhibits Human Platelet Aggregation Induced by Multiple Agonists

Cardiovascular diseases such as hypertension, myocardial infarction, and atherosclerosis are the major cause of morbidity and mortality in humankind and not only afflict industrialized nations but also affect developing countries such as Pakistan. We attempted to screen one of the most common fruits, Malus domestica (MD or apple), used in Pakistan for its potential cardio-protective effects. The crude aqueous extract (MD-Aq) was prepared and investigated for inhibitory activity against several important cardiovascular drug targets. Activities of antioxidant enzymes such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) were studied, as well as total antioxidant status (TAS). Calcium channel blocking activity was measured using guinea pig ileum in an isolated tissue bath setup. Platelet aggregation studies were carried out using a dual-channel aggregometer. MD-Aq showed dose-dependent improvement in the GPX activity. The highest SOD levels were observed with 10 mg/ml and were 185 U/L compared to 174 U/L for saline, which means no significant effect by MD-Aq. TAS levels were highest at 10 mg/ml of MD-Aq, reaching 1.75 mmol/L of plasma. At 10 mg/ml, close to 90% inhibition of KCl-induced opening of calcium channels was observed, compared with the effect of 1mM Verapamil. At each dose of 1, 5, and 10 mg/ml, a significantly higher arachidonic acid-induced inhibition of platelet aggregation was observed as compared to the saline effect. MD-Aq effects on platelet-activating factor-induced platelet aggregation were less potent. We concluded that MD-Aq could elevate GPX and TAS levels, is inactive at SOD, and is excellent as a calcium channel blocker, a more potent blocker of arachidonic acid-induced aggregation than platelet-activating factor-induced aggregation. These activities can help treat various cardiovascular diseases.

Effect of Dihydroartemisinin on contractility to Drugs in isolated smooth muscle Preparations in guinea pig in vitro models

This study was aimed at evaluating the effect of Dihydroartemisinin (DHA)on contractility to drugs in ileum isolated smooth muscle preparations in guinea pigs using in Vitro experimental procedures / standard protocols in an organ bath set up. dihydroartemisinin (1.0 x 10 - 8 - 1.0 x 10 – 5mg/mL) when applied alone and separately excited marked variable effects on guinea pig ileum . In some preparation it showed no response, while in others it produced slight phasic contraction when external calcium (Ca2+) ion was introduced. The slight phasic contractile activity was abolished by verapamil (5x10-3mg/mL). Dihydroartemisinin (1.0 x 10 - 6 - 1.0 x 10 – 5mg/mL) caused marked significant induced contraction – dependent inhibition of acetylcholine, potassium chloride and histamine in depolarizing tyrode solution (p &lt; 0.05).The Inhibitory response maxima of dihydroartemisinin on acetylcholine induced contraction is 17.0±0.1 mm(65.56% inhibition) ; and is moderate when compared to the inhibitory effect of atropine (10-5 M). The result shows that dihydroartemisinin seems to act via non-specific receptor mechanism, with appreciable calcium channel blocking activity and it is safe at therapeutic doses.

Synthesis, Biological Evaluation, in silico ADMET and Molecular Docking of new 1,4‐Dihydropyridine Derivatives Bearing Ether Substitution as Calcium Channel Blockers

AbstractA set of 1,4‐dihydropyridine derivatives were synthesized, possessing methyl or ethyl esters at positions 3 and 5, an aliphatic or aromatic ether group at position 2, and a thienyl ring at position 4. The calcium channel blocking activity of these derivatives was investigated using K+‐induced contraction on the longitudinal smooth muscles of guinea pig ileum (GPILSM). Our findings showed that the derivatives had IC50 ranging from 0.5 to 5.2 μM. Among the synthesized compounds, compound including methoxy group in position 2 and ethyl acetate in positions 3 and 5, with IC50=0.55±0.58 μM was almost comparable to that of nifedipine (IC50=0.27±1.23 μM). The results of docking studies and biological evaluation of synthetic compounds were consistent. According to the physicochemical and drug‐likeness parameters, it is predicted that the synthesized compounds can be a suitable candidate for calcium channel blocking.

Detection and isolation of intestinal muscle relaxant substances from the root of Taverniera abyssinica A. Rich

Ethnopharmacological relevanceIn Ethiopian traditional medicine the root of Taverniera abyssinica A.Rich is known as a remedy for sudden gastrointestinal cramping and fever. In this study we have isolated and identified the bioactive principle of Taverniera abyssinica that exerts effects on isolated smooth muscle tissues of the rabbit duodenum and guinea-pig ileum. Aim of the studyTo isolate and purify the bioactive principle from the root of Taverniera abyssinica A.Rich by bioassay-guided fractionation, HPLC purification and masspectrometry, with further investigation of its bioactivity on isolated smooth muscle strips. Materials and methodsRoots of Taverniera abyssinica A.Rich extracted in 75% methanol/water were fractioned with a reverse phase column and then subjected to HPLC purification. Each fraction collected from the HPLC was tested for its bioactivity using electric field stimulation-evoked contractions of the rabbit duodenum and guinea-pig ileum. Finally, detailed structural analysis of the fraction displaying significant bioactivity was made by mass spectrometry. ResultsThrough bioassay-guided fractionation and HPLC purification the bioactive fractions were identified. These were tested for bioactivity on isolated smooth muscle strips which showed about 80% inhibition of contractions evoked by electric field stimulation. These compounds were identified as formononetin, afrormosin and tectorigenin by using masspectrometry applying relevant standards for detection. ConclusionThe traditionally claimed smooth muscle-relaxing effect of the roots of Taverniera abyssinica A.Rich is essentially due the three isolated and purified the two isoflavones formononetin, afrormosin as well as the metoxyisoflavone tectorigenin, along with possibly other not yet purified bioactive substances, however with similar smooth muscle-relaxing properties.

Antagonistic effect of mepyramine and tubocurarine on the histamine-mediated contraction of intestinal smooth muscle cells

Introduction: Histamine is an endogenous ligand which exerts its biological actions by binding to 4 subtypes of histamine receptors (HR). Its effects on the gastrointestinal tract are complex being the dominant effect contraction of muscle cells.&#x0D; Method: The aim of this study was to verify the antagonistic effect of mepyramine (10-10M - 10-7M) and tubocurarine (10-7M - 10-4M) in the contractile action of histamine (10-11M - 10-4M). in guinea pig ileum, for this purpose it was used the program Virtual Organ Bath 16 V 2.8, which allow quantify the change in strength(g) produced by smooth muscle contraction in the presence of these substances. Concentration-response curves were obtained through GraphPad Prism® graphic program. The determination of the competitive nature of the antagonist and the calculation of the affinity constant was performed through Schild method.&#x0D; Results: Mepyramine is a competitive antagonist of histamine (10-10M to 10-7M), making it a potential therapeutic agent for the treatment of irritable bowel syndrome. On the other hand, it is not understood that tubocurarine is an antagonist of histamine receptors.&#x0D; Conclusions: The results obtained provide evidence that the contractile effect of histamine on the smooth muscle of intestinal cells isolated from guinea pig is competitively antagonized by mepyramine. In addition, by calculating the pKB parameter, it was found that this compound has greater potency than other antihistamines.

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)

The Analysis of Transcriptomes and Microorganisms Reveals Differences between the Intestinal Segments of Guinea Pigs

The intestine is a tubular organ with multiple functions such as digestion absorption and immunity, but the functions of each intestinal segments are different. Intestinal regionalization is necessary for normal physiological function, but it also means the research results obtained at specific sites may not be applicable to other intestinal segments. In order to comprehensively describe the functional changes in the intestine, different intestinal segments and their contents (duodenum, jejunum, ileum, cecum, colon, and rectum) of guinea pigs were collected for RNA seq and 16S rRNA seq, respectively. The results showed differential genes of each intestinal segment mainly involve mucosa, digestion, absorption, and immunity. The gene sets related to fat, bill salts, vitamins, aggregates, amino acids, and water absorption were highly expressed in the small intestine, and the gene sets related to metal ions, nucleotides, and SCFAs were highly expressed in the large intestine. In terms of immunity, the CD8+ T, Th1, eosinophils, pDCs, and natural killer (NK) T cells in the small intestine showed higher scores than those in the large intestine, while the pattern-recognition receptor signaling pathway-related genes are highly expressed in the large intestine. In terms of microbial composition, Proteobacteria and Actinobacteria are abundant in the small intestine, while Firmicutes and Spirochaete are abundant in large intestine. The correlation analysis showed a high correlation between intestinal microorganisms and gene modules related to digestion and absorption. In addition, cross-species analysis showed the SCFA metabolism gene expression trends in human and rodent intestine were different. In conclusion, we analyzed the changes in substance transport, immune and microbial composition between different intestinal segments of guinea pigs, and explored the relationship between intestinal transcriptome and microorganisms, our research will provides a reference for subsequent intestinal-related research.

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.

Preclinical Studies to Evaluate the Gut Stimulatory Activity of Aloe Musabbar.

Background Constipation is a common functional gastrointestinal disorder. Medicines derived from nature are routinely used to treat it. The present study evaluates the gut stimulatory activity of Aloe musabbar (processed powder of Aloe vera) using in vitro and in vivo models for gut stimulatory activity. Materials and Methods In vitro tests were conducted on isolated rat colon, guinea pig ileum, and rabbit jejunum, while in vivo study was performed using mice intestinal transit time. Aloe musabbar (A. musabbar) was tested at doses 0.2–200 mg/mL (in-vitro study) and 86.6 mg/kg (in vivo study). In vitro studies were done in the presence and absence of atropine sulphate (1 ng/ml). The results were statistically analyzed, and p < 0.05 was considered to indicate the significance. Results A. musabbar exhibited dose-dependent increase in the smooth muscle contraction of isolated gut tissues. Presence of atropine minimized the contractile responses and shifted the dose-response curves towards the right-hand side. The intestinal transit time in mice was observed to be increased significantly (p < 0.01) in A. musabbar-treated animals, when compared with normal animals. Conclusion A mild smooth muscle contraction induced by A. musabbar suggests that it can stimulate intestinal bowel movement without causing spasms. The diminished responses in the presence of atropine indicated that the gut stimulatory activity could be mediated partially through parasympathetic innervations. More studies are needed to determine the precise mechanism of action including the specific active ingredient responsible for the gut stimulatory activity.

Cortistatin Inhibits Intestinal Ion Secretion via Activating the Somatostatin‐2 Receptor in the Submucosal Neurons of the Mouse Colon

Background and AimsCortistatin (CST) is a somatostatin‐like neuropeptide that is found in both the central and peripheral nervous system. CST binds with high affinity to all somatostatin receptors and also has actions not shared by somatostatin. We previously found that CST is expressed by enteric neurons in the guinea pig ileum and acts as an inhibitory neurotransmitter in the submucosal plexus. The aim of the present study was to evaluate the effect of CST on neurogenic intestinal secretion.MethodsMucosal/submucosal flat‐sheet preparations from mouse proximal colon were mounted in Ussing flux chambers for measurement of short‐circuit current (Isc) as an indicator of mucosal secretion. Transmural electrical field stimulation (EFS) evoked characteristic biphasic increases in Isc, with an early rapidly rising phase followed by a sustained phase.ResultsApplication of CST‐14, CST‐17, or CST‐29 to the basolateral side of the mucosal/submucosal preparation decreased baseline Isc in a concentration‐dependent manner with an IC50 of 90.5 nM, 52.1 nM, or 102.9 nM, respectively. The somatostatin‐2 receptor (SSTR‐2) antagonist CYN 154806 (1 mM) significantly suppressed CST‐14 (100 nM), CST‐17 (100 nM), or CST‐29 (100 nM)‐evoked ΔIsc by 36.0 ± 8.2% (n=5; P &lt; 0.05), 47.2 ± 11.2% (n=5; P &lt; 0.01), or 51.7.0 ± 8.4% (n=5; P &lt; 0.01), respectively. The neuronal blocker tetrodotoxin (300 nM) significantly reduced CST‐14 (100 nM), CST‐17 (100 nM), or CST‐29 (100 nM)‐evoked ΔIsc by 36.5 ± 2.7% (n=5; P &lt; 0.01), 48.9 ± 11.2% (n=5; P &lt; 0.01), or 49.5 ± 3.6% (n=5; P &lt; 0.01), respectively. All of the CSTs (1 nM – 1 mM) also produced a concentration‐dependent reduction of the EFS‐evoked biphasic secretory responses. The effect of CSTs on the EFS‐evoked responses was antagonized by CYN 154806 (1 mM). Immunohistochemical staining with a CST‐17 polyclonal antibody revealed expression of CST‐17 immunoreactivity (IR) in mouse colonic submucosal neurons. CST‐17‐IR was localized in cholinergic secretomotor neurons but was absent from non‐cholinergic secretomotor neurons and calbindin‐IR neurons.ConclusionsThe results suggest that CST acts at SST‐2 receptors in the submucosal plexus to suppress secretomotor neuronal excitability and neurogenic intestinal secretion in the mouse colon.

Evaluation of the Laxative-Like Activity of Andrographis Paniculata

Herbal medicine has been used since ancient times to treat chronic constipation. The present study has investigated the gut stimulatory activity of Andrographis peniculata, an herbal medicine common to many parts of the globe. Results of these studies show a dose-dependent increase in the contraction of smooth muscle from isolated rat colon, guinea pig ileum, and rabbit jejunum by A. peniculata extracts. Furthermore, it enhanced intestinal fecal transit in mice. Additional studies into its action suggested the involvement of a cholinergic mechanism.

Olea europea L. Leaves and Hibiscus sabdariffa L. Petals Extracts: Herbal Mix from Cardiovascular Network Target to Gut Motility Dysfunction Application.

It is well known that diet and nutrition play a critical role in the etiopathogenesis of many disorders. On the other hand, nutrients or bioactive compounds can specifically target and control various aspects of the mechanism underlying the pathology itself, and, in this context, diseases related to intestinal motility disorders stand out. The Herbal Mix (HM) consisting of Olea europea L. leaf (OEE) and Hibiscus sabdariffa L. (HSE) extracts (13:2) has been proven to be a promising nutraceutical option for many diseases, but its potential in inflammatory-driven gastrointestinal disorders is still unexplored. In this study, HM effects on guinea-pig ileum and colon contractility (induced or spontaneous) and on human iNOS activity, as well as on human colorectal adenocarcinoma Caco-2 cells, were studied. Results showed that the HM can control the ileum and colon contractility without blocking the progression of the food bolus, can selectively inhibit iNOS and possesses a strong pro-apoptotic activity towards Caco-2 cells. In conclusion, the present results suggest that, in some diseases, such as those related to motility disorders, an appropriate nutritional approach can be accompanied by a correct use of nutraceuticals that could help not only in ameliorating the symptoms but also in preventing more severe, cancer-related conditions.