Brain Perception of Different Oils on Appetite Regulation: An Anorectic Gene Expression Pattern in the Hypothalamus Dependent on the Vagus Nerve.

(1) Background: We examined the effect of the acute administration of olive oil (EVOO), linseed oil (GLO), soybean oil (SO), and palm oil (PO) on gastric motility and appetite in rats. (2) Methods: We assessed food intake, gastric retention (GR), and gene expression in all groups. (3) Results: Both EVOO and GLO were found to enhance the rate of stomach retention, leading to a decrease in hunger. On the other hand, the reduction in food intake caused by SO was accompanied by delayed effects on stomach retention. PO caused an alteration in the mRNA expression of NPY, POMC, and CART. Although PO increased stomach retention after 180 min, it did not affect food intake. It was subsequently verified that the absence of an autonomic reaction did not nullify the influence of EVOO in reducing food consumption. Moreover, in the absence of parasympathetic responses, animals that received PO exhibited a significant decrease in food consumption, probably mediated by lower NPY expression. (4) Conclusions: This study discovered that different oils induce various effects on parameters related to food consumption. Specifically, EVOO reduces food consumption primarily through its impact on the gastrointestinal tract, making it a recommended adjunct for weight loss. Conversely, the intake of PO limits food consumption in the absence of an autonomic reaction, but it is not advised due to its contribution to the development of cardiometabolic disorders.

Nandrolone decanoate impairs gastrointestinal motility and duodenal morphometry in moderately exercised rats.

The misuse of anabolic androgenic steroid associated or not with physical workouts disrupts gastrointestinal (GI) function homeostasis. Our goal was to investigate the effects of nandrolone decanoate (ND) and moderate swimming on the GI transit of solid meals, GI motor contractility, and intestinal histology in rats. Male Wistar rats were allocated to four groups that received intramuscular injections of ND (5.0 mg/kg) or vehicle (60.0 µL) and were submitted or not to swimming sessions (60 min, 5% body weight overload) for 4 weeks. Gastric emptying, intestinal transit, in vitro GI contractility, intestinal morphometry, and duodenal mucosal mast cells were evaluated in all experimental groups. ND treatment accelerated gastric emptying, slowed small intestine transit time, enhanced gastric carbachol-mediated reactivity, decreased crypt depth and villus height, reduced mucosal thickness, and increased the circular and longitudinal muscle layer thickness of the duodenum in sedentary rats. Moderate exercise accelerated intestinal transit time and reduced submucosa thickness. In vehicle-treated animals, a strong negative correlation was found between intestinal transit and mucosal mast cells, which was reversed by ND treatment. Combining ND treatment and swimming accelerated gastric emptying, increased duodenal cholinergic reactivity, inhibited the sodium nitroprusside relaxing response, increased the number of duodenal mast cells, decreased villus height, and increased the thickness of all muscle layers. ND changed the morphological and functional properties of the GI tract over time, with intense dysmotility, especially in sedentary animals, but moderate exercise seemed to have played a compensatory role in these harmful effects in the gut.

Efectos en la motilidad de fármacos para obesidad: impacto en la práctica clínica y endoscópica / Effects of obesity drugs on gastrointestinal motility: impact on clinical and endoscopic practice

Obesity is a very common pathology worldwide. Among the management alternatives are glucagon-like peptide-1 (GLP-1) analogues, a hormone secreted mainly by the intestine. Apart from its effects as an incretin, effects on gastrointestinal motility have been described, which seem to be fundamental for its effect on obesity, but also the cause of its most frequent potential adverse effects. There is discussion regarding the large number of case reports in relation to the retention of gastric contents at the time of endoscopy. There is currently insufficient evidence to state categorically that they produce a significant change in gastric emptying. Nevertheless, it is recommended to inquire about the use of these drugs before endoscopic procedures that require sedation and, in the presence of symptoms, to suggest changes in the preparation

La obesidad es una patología muy frecuente a nivel global. Dentro de las alternativas del manejo están los análogos del péptido 1 similar al glucagón (GLP-1), hormona secretada principalmente por el intestino. Aparte de sus efec- tos como incretina, se han descrito efectos sobre la motilidad gastrointestinal, los que parecen ser fundamentales para su efecto sobre la obesidad, pero también los causales de sus potenciales efectos adversos más frecuentes. Existe discusión en relación con la gran cantidad de reportes de casos en relación con la retención de contenido gástrico al momento de una endoscopia. Actualmente no existe evidencia suficiente para afirmar categóricamente que producen un cambio significativo en el vaciamiento gástrico. No obstante, se recomienda indagar sobre el uso de estos fármacos antes de procedimientos endoscópicos que requieran sedación y, ante la presencia de síntomas, sugerir cambios en la preparación.

Does L-carnitine prevent cadmium-induced damage in gastrointestinal contractility and histological changes in prepubertal rat / ¿La L-carnitina previene el daño inducido por cadmio en la contractilidad gastrointestinal y los cambios histológicos en ratas prepúberes?

SUMMARY: Cadmium (Cd) is the industrial and environmental toxic heavy metal which is found in air, water and soil. Cd, adversely affects many organs in humans such as kidney, intestine, liver, testis and lungs. L-carnitine (LC) is an important agent that plays essential role in energy metabolism. In our study, we aimed to work out whether LC application has any protective effect on intestinal contractility and morphologic damage of prepubertal rat duodenum on Cd-induced toxicity. Twenty eight prepubertal female Wistar rats were divided into four groups. The first group is control (C), second group; Cd group; Cadmium chloride was given 2 mg/kg 28 days with a one-day break by i.p. The third group; Cd+LC, which cadmium chloride was given 2 mg/kg i.p. and LC was given orally by gastric lavage. The LC dose was given as 75 mg/kg. The fourth group; LC, which only LC was given orally. The intestinal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (ACh) and relaxation was achieved with phenylephrine. Also the segments were examined for histological changes by light microscopy. Ach-induced contractions were higher in Cd+LC, LC, and control group compared to the Cd group in duodenal segments. The phenylephrine-induced relaxations were lower in Cd groups as compared with Control, Cd+LC and LC group in duodenal segments. In Cd group intestinal morphology was observed to be severely damaged whereas in Cd+LC group the damage was noticeably lower. Cd administration caused severe cellular damage and decreased gastrointestinal motility. Treatment with the LC has affected the gastrointestinal contractility and reduced the damage in intestinal morphology, which occured after Cd application.

El cadmio (Cd) es el metal pesado tóxico industrial y ambiental que se encuentra en el aire, el agua y el suelo. El Cd afecta negativamente a muchos órganos humanos, como los riñones, los intestinos, el hígado, los testículos y los pulmones. La L-carnitina (LC) es un agente importante que juega un rol esencial en el metabolismo energético. El objetivo de este estudio fue determinar si la aplicación de LC tiene algún efecto protector sobre la contractilidad intestinal y el daño morfológico del duodeno de rata prepuberal sobre la toxicidad inducida por Cd. Veintiocho ratas Wistar hembras prepúberes se dividieron en cuatro grupos. El primer grupo control (C), segundo grupo; grupo cd; Se administró cloruro de cadmio 2 mg/kg durante 28 días con un descanso de un día por vía i.p. El tercer grupo; Cd+LC, al que se administró cloruro de cadmio 2 mg/kg i.p. y LC se administró por vía oral mediante lavado gástrico. La dosis de LC se administró como 75 mg/kg. El cuarto grupo; LC, al cual solo LC se administraba por vía oral. Los segmentos intestinales fueron aislados y suspendieron en baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (ACh) y la relajación se logró con fenilefrina. También se examinaron los segmentos en busca de cambios histológicos mediante microscopía óptica. Las contracciones inducidas por Ach fueron mayores en Cd+LC, LC y el grupo control en comparación con el grupo Cd en los segmentos duodenales. Las relajaciones inducidas por fenilefrina fueron menores en los grupos Cd en comparación con el grupo Control, Cd+LC y LC en los segmentos duodenales. En el grupo Cd se observó que la morfología intestinal estaba severamente dañada mientras que en el grupo Cd+LC el daño fue notablemente menor. La administración de Cd causó daño celular severo y disminución de la motilidad gastrointestinal. El tratamiento con LC afectó la contractilidad gastrointestinal y redujo el daño en la morfología intestinal, que ocurría después de la aplicación de Cd.

The effects of L-carnitine on gastrointestinal contractility and histological changes in rat intestinal ischemia-reperfusion Injury / Efectos de la l-carnitina sobre la contractilidad gastrointestinal y los cambios histológicos en la lesión por isquemia-reperfusión intestinal de rata

SUMMARY: Ischemia-reperfusion (I/R) of the small intestine causes serious abdominal pathologies including tissue dysfunction and organ failure. L-carnitine (L-C), a powerful antioxidant, may help lessen the severity of these pathological effects since it plays a key role in energy metabolism. In this work we aimed to study the effects of L-C on the isolated ileal and duodenal contractility and histological changes in intestinal ischemia and reperfusion injury. Twenty eight Wistar rats were divided into four groups. The first group is the control group. Second group, I/R group, had rats submitted to 45-minutes of intestinal ischemia and to 45-minutes reperfusion. The third group, I/R+ L-C group, rats were treated with L-C 5 minutes before reperfusion and than submitted to ischemia. The fourth group, included rats that were treated with L-C without ischemia or reperfusion. Intestinal ischemia was conducted by obstructing superior mesentery arteries by silk loop. The ileal and duodenal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (Ach) and relaxation was achieved with phenylephrine. At the same time the terminal ileal and duodenal segments were examined for histological changes. Ach-induced contraction responses were higher in the I/R+L-C group, the L-C group, and the control group compared to the I/R group, in both ileal and duodenal segments. On the other hand, the phenylephrine-induced relaxations were higher in the I/R+L-C and L-C groups, especially in duodenal segments. In I/R group intestinal morphology was observed to be severely damaged whereas in I/R+L-C group the damage was noticeably lower possibly due to protective properties of L-C. I/R injury caused severe cellular damage response within the muscularis resulting in decreased gastrointestinal motility. Treatment with the L-C has significantly affected the gastrointestinal contractility. Also L-C treatment reduced the damage in intestinal morphology that occurs after IR injury.

RESUMEN: La isquemia-reperfusión (I/R) del intestino delgado provoca graves patologías abdominales que incluyen disfunción tisular y falla orgánica. La L-carnitina (L-C), un poderoso antioxidante, puede ayudar a disminuir la gravedad de estos efectos patológicos, ya que desempeña un papel clave en el metabolismo energético. El objetivo de este trabajo fue estudiar los efectos de L-C sobre la contractilidad ileal y duodenal aislada y los cambios histológicos en la lesión por isquemia y reperfusión intestinal. Se dividieron 28 ratas Wistar en cuatro grupos. El primer grupo fue el control. El segundo grupo, grupo I/R, de ratas sometidas durante 45 minutos de isquemia intestinal y a 45 minutos de reperfusión. El tercer grupo, grupo I/R+ L-C, las ratas se trataron con L-C, 5 minutos antes de la reperfusión y luego se sometieron a isquemia. El cuarto grupo, las ratas fueron tratadas con L-C sin isquemia ni reperfusión. La isquemia intestinal se realizó obstruyendo la arteria mesentérica superior con un asa de seda. Los segmentos ileal y duodenal se aislaron y suspendieron en un baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (Ach) y la relajación se logró con fenilefrina. Al mismo tiempo, se examinaron cambios histológicos de los segmentos del íleon terminal y del duodeno. Las respuestas de contracción inducidas por Ach fueron mayores en el grupo I/R+L-C, el grupo L-C y el grupo control en comparación con el grupo I/R, tanto en el segmento ileal como en el duodenal. Por otra parte, las relajaciones inducidas por fenilefrina fueron mayores en los grupos I/R+L-C y L-C, especialmente en los segmentos duodenales. En el grupo I/R se observó que la morfología intestinal estaba dañada significativamente, mientras que en el grupo I/R+L-C el daño fue notablemente menor, posiblemente debido a las propiedades protectoras de L-C. La lesión por I/R causó una respuesta de daño celular severo dentro de la capa muscular que resultó en una disminución de la motilidad gastrointestinal. El tratamiento con L-C afectó significativamente la contractilidad gastrointestinal. Por otra parte, el tratamiento L-C redujo el daño en la morfología intestinal que ocurre después de la lesión por IR.

L-Glutamine and Physical Exercise Prevent Intestinal Inflammation and Oxidative Stress Without Improving Gastric Dysmotility in Rats with Ulcerative Colitis.

The aim of this study was to evaluate the effects of glutamine supplementation or exercise on gastric emptying and intestinal inflammation in rats with ulcerative colitis (UC). Strength exercise consisted of jump training 4 × 10 repetitions/5 days a week/8 weeks with progressive overload. Endurance exercise consisted of swimming without overload for a period of 1 h a day/5 days a week/8 weeks. Another group (sedentary) of animals was supplemented with L-glutamine (1 g/kg of body weight) orally for 8 weeks before induction of UC. Colitis was induced by intra-colonic administration of 1 mL of 4% acetic acid. We assessed gastric emptying, macroscopic and microscopic scoring, oxidative stress markers, and IL-1ß, IL-6, and (TNF-α) levels. The UC significantly increased (p < 0.05) the gastric emptying compared with the saline control group. We observed a significantly decrease (p < 0.05) in body weight gain in UC rats compared with the control groups. Both exercise interventions and L-glutamine supplementation significantly prevented (p < 0.05) weight loss compared with the UC group. Strength and endurance exercises significantly prevented (p < 0.05) the increase of microscopic scores and oxidative stress (p < 0.05). L-glutamine supplementation in UC rats prevented hemorrhagic damage and improved oxidative stress markers (p < 0.05). Strength and endurance exercises and glutamine decreased the concentrations of inflammatory cytokines IL-1ß, IL-6, and TNF-α compared with the UC group (p < 0.05). Strength and endurance exercises and L-glutamine supplementation prevented intestinal inflammation and improved cytokines and oxidative stress levels without altering gastric dysmotility in rats with UC.

Investigation of ethnomedicinal use of Commiphora leptophloeos (Mart.) J. B. Gillett (Burseraceae) in treatment of diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Commiphora leptophloeos (Mart.) J.B. Gillett, popularly known as "imburana", "imburana-de-cheiro" or "imburana-de-espinho", has been used in folk medicine for the treatment of gastrointestinal diseases, such as diarrhea. The indian tribes "Kairir-Shokó and shokó use the bark to treat diarrhea. However, there is no scientific evidence to justify the therapeutic use of this species. AIM OF THE STUDY: To investigate the ethnomedicinal use of Commiphora leptophloeos, with respect to the antimicrobial, antisecretory, antimotility and antispasmodic activities of the crude ethanolic extract obtained from its leaves (CL-EtOHL) and the mechanism underlying this action in rodents. MATERIAL AND METHODS: In the evaluation of antibacterial and antifungal activities was determined the minimum inhibitory concentration (MIC) of the extract, against different strains of bacteria and fungi. All experimental protocols were approved by the Animal Ethics Committee of the Federal University of Paraíba (045/2016). In addition, behavioral screening and acute toxicity assessment of CL-EtOHL were performed in female mice (n = 6). In the investigation of antidiarrheal activity (n = 6), frequency of defecation and number of liquid stools, were classified during 4 h, and intestinal fluid and transit were measured. In addition, the antispasmodic effect on rat ileum (n = 5) was also investigated. RESULTS: The ethanolic extract is rich in flavonoids and the main were identified as C-glycosylated flavonoids (isoorientin, orientin, and vitexin). In the evaluation of antimicrobial and antifungal activity, the extract showed moderate efficacy only against the tested strains of Candida krusei ATCC-6258, Candida parapsilosis ATCC-22019 and Candida glabrata ATCC-90030. The extract had no toxic effect until 2000 mg/kg. In castor oil-induced diarrhea, CL-EtOHL inhibited, in a dose-dependent manner, both total defecation frequency (ED50 = 380.4 ± 145.4 mg/kg) and the number of watery stools (ED50 = 151.2 ± 76.3 mg/kg). The extract showed no effect on fluid accumulation or normal intestinal transit. On the other hand, when the animals were pretreated with castor oil, the extract decreased the distance traveled by the activated charcoal (ED50 = 177.0 ± 50.3 mg/kg). In the investigation of antispasmodic effect, CL-EtOHL antagonized the contractions induced by KCl 30 mM (IC50 = 208.2 ± 25.9 µg/mL) and CCh 10-6 M (IC50 = 95. ± 22.0 µg/mL). To verify the participation of muscarinic receptors in this effect, cumulative carbachol curves were performed in the absence and presence of the extract, and a non-competitive pseudo-irreversible antagonism of these receptors was observed. CONCLUSION: The data indicate that ethanol extract obtained from the leaves of Commiphora leptophloeos has an antidiarrheal effect due to inhibition of the intestinal motility and antispasmodic effect, through the antagonism of muscarinic receptors. In addition, we suggest that flavonoids isolated from CL-EtOHL may be responsible for antidiarrheal activity of this extract. This explains its ethnomedicinal use in the treatment of diarrhea.

Pharmacologycal activity of peperina (Minthostachys verticillata) on gastrointestinal tract.

ETHNOPHARMACOLOGICAL RELEVANCE: Minthostachys verticillata (Griseb.) Epling (Lamiaceae), known as Peperina is a medicinal native plant, with a traditional use as a digestive, antispasmodic and antidiarrheic. AIM OF THE STUDY: Despite its folkloric use, no scientific evaluation of this plant related to the gastrointestinal inflammatory process has been carried out to date. The present study aims to assess the effects of M. verticillata on gastrointestinal system in experimental models. MATERIALS AND METHODS: M. verticillata (250 and 500 mg/kg) was orally tested in a colitis model induced by acetic acid. Colon weight/length ratio, oxidative stress (oxidized and reduced glutathione), histological changes using Alcian blue and hematoxylin & eosin staining and expression of IL1ß, TNFα, iNOS, COX-2 were evaluated. The effect of the extract in three additional in vivo models were studied: intestinal motility and diarrhea induced by ricin oil, and visceral pain induced by intracolonic administration of capsaicin. Finally, the activity on concentration response curves of acetylcholine, calcium chloride, potassium and serotonin were achieved in isolated rat jejunum. RESULTS: In the colitis model, M. verticillata induced a significant reduction in the colon weight/length ratio, oxidative stress and expression levels of IL-1ß, iNOS and COX-2. Also, the extract diminished the severity of microscopic tissue damage and showed protective effect on goblet cells. Intestinal motility, diarrhea, visceral pain-related behaviors and referred hyperalgesia were significantly reduced when the animals were treated with the extract. Furthermore, in isolated jejunum, M. verticillata significantly reduced the contraction induced by serotonin and acetylcholine. Likewise, the extract non-competitively inhibited the response-concentration induced by CaCl2 and inhibited both low and high K+-induced contractions. CONCLUSIONS: This is the first study to validate traditional use of M. verticillata for digestive disorders and demonstrated that its aqueous extract could represent a promising strategy in targeting the multifactorial pathophysiology of inflammatory bowel disease.

The effect of probiotics on intestinal motility in an experimental short bowel model.

PURPOSE: To investigate the effect of probiotics on spontaneous contractions of smooth muscle isolated from jejunum and ileum of rat model. METHODS: Four rat groups were created (n=8, in each) including control (Group 1), control+probiotic (Group 2), short bowel (Group 3), and short bowel+probiotic (Group 4). Groups 1 and 2 underwent sham operation, Groups 3 and 4 underwent massive bowel resection. Bifidobacterium Lactis was administered in Groups 2 and 4 daily (P.O.) for three weeks. On postoperative week 3, rats were sacrificed, and jejunum and ileum smooth muscle were isolated for organ bath. Muscle contraction changes were analyzed before and after addition of antagonists. RESULTS: Short bowel group exhibited increased amplitude and frequency of spontaneous contractions. The addition of probiotics significantly decreased enhanced amplitude and frequency of bowel contraction in short bowel group and returned to control values. L-NNA increased amplitude and frequency of contractions in all groups. While indomethacin and nimesulide increased the amplitude in all groups, the frequency was only increased in jejunum. Hexamethonium and tetrodotoxin did not change the contraction characteristics in all groups. CONCLUSION: We suggest that early use of probiotics may significantly regulate bowel motility, and accordingly improve absorption of nutrients in short bowel syndrome.

Maytenus robusta Reissek, a medicinal plant popularly used to treat digestive diseases, promotes ameliorative effects in colon and liver of mice exposed to dextran sulfate sodium.

ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus robusta Reissek (Celesteraceae), popularly named as cafezinho do mato or coração de bugre, is employed to treat inflammatory digestive diseases in the south of Brazil. However, despite popular usage, the effects of this species on an experimental model of ulcerative colitis are unknown. AIM OF THE STUDY: To evaluate the effects of M. robusta extract (HEMR) on colon and liver from mice with colitis induced by dextran sulfate sodium (DSS). MATERIALS AND METHODS: Firstly, the cytotoxicity of HEMR and its effects on ROS and nitrite production in IEC-6 cells were evaluated. The experimental colitis was established by adding 3% DSS on drinking water of mice and the effects of HEMR (1-100 mg/kg, p.o, once a day by 7 days) in colonic and hepatic tissues were analyzed. RESULTS: The HEMR (1-100 µg/mL) did not alter the cell viability but reduced nitrite production of IEC-6 stimulated by LPS. Moreover, HEMR (100 mg/Kg) attenuates macro and microscopic alterations in the colon from mice exposed to DSS, as evidenced by a reduction of the colon shortening, attenuation of the epithelial erosion, submucosal edema and preservation of the Goblet cells integrity, as well as the restoration of mucin depletion. The treatment with HEMR increased GSH amount, reduced LOOH levels and normalizes CAT activity in the colon. The group treated with HEMR showed increased GST activity, reduced MPO activity and decreased inflammatory cytokines secretion (TNF and IL-6) in the colonic tissue. In the liver, HEMR increased GST activity, decreased the GPx activity and reduced IL-6 levels. Furthermore, the HEMR treatment reduced AST and ALT serum levels in mice exposed to DSS. Finally, the HEMR was able to reduce intestinal transit. CONCLUSIONS: HEMR treatment minimizes inflammation of the colon and maintaining the antioxidant homeostasis. In addition, HEMR may be a potential tool to prevent hepatic injury secondary to ulcerative colitis.

Antidiarrheal activity of farnesol in rodents: Pharmacological actions and molecular docking.

Diarrhea is a condition in which the individual has about three or more daily bowel movements, followed by changes in stool consistency. It is currently considered as one of the worst public health problems due to the number of cases and deaths involved and difficulty of treatment. Thus, the use of natural products is an alternative for new treatments. Among these possibilities is Farnesol (C15H26O), a sesquiterpene found in different herbal species that has known biological activities. The objective of this study was to evaluate the antidiarrheal activity of Farnesol (FOH). Initially, FOH activity was evaluated in models of diarrhea and enteropooling induced by castor oil and PGE2. To evaluate motility, the opioid and cholinergic pathways were studied. In addition, the effect of FOH was investigated in the secretion model in intestinal loops treated with cholera toxin. FOH was evaluated for the ability to absorb fluids in intestinal loops and interact with GM1 receptors using the ELISA method and molecular docking. The dose of 50 mg/kg of FOH showed the best results in all antidiarrheal activity tests with castor oil and PGE2, being considered as the standard dose, reducing motility by anticholinergic mechanisms. There was a reduction in fluid secretion when FOH interacted directly with GM1 receptors; cholera toxin and molecular docking showed strong interaction between farnesol and these targets. In view of the results presented, the antidiarrheal activity occurs through anticholinergic, anti-inflammatory and anti-secretory action, making farnesol a potential candidate for the development of a new drug to treat diarrheal diseases.

The effect of probiotics on ıntestinal motility in an experimental short bowel model

Abstract Purpose To investigate the effect of probiotics on spontaneous contractions of smooth muscle isolated from jejunum and ileum of rat model. Methods Four rat groups were created (n=8, in each) including control (Group 1), control+probiotic (Group 2), short bowel (Group 3), and short bowel+probiotic (Group 4). Groups 1 and 2 underwent sham operation, Groups 3 and 4 underwent massive bowel resection. Bifidobacterium Lactis was administered in Groups 2 and 4 daily (P.O.) for three weeks. On postoperative week 3, rats were sacrificed, and jejunum and ileum smooth muscle were isolated for organ bath. Muscle contraction changes were analyzed before and after addition of antagonists. Results Short bowel group exhibited increased amplitude and frequency of spontaneous contractions. The addition of probiotics significantly decreased enhanced amplitude and frequency of bowel contraction in short bowel group and returned to control values. L-NNA increased amplitude and frequency of contractions in all groups. While indomethacin and nimesulide increased the amplitude in all groups, the frequency was only increased in jejunum. Hexamethonium and tetrodotoxin did not change the contraction characteristics in all groups. Conclusion We suggest that early use of probiotics may significantly regulate bowel motility, and accordingly improve absorption of nutrients in short bowel syndrome.

The Effects of Supplementing Hancornia speciosa (Mangaba) on Bowel Motility and Inflammatory Profile of Wistar Rats.

The prevalence of gastrointestinal disorders, such as constipation, has been increasing. Genetic factors and lifestyle are some of the etiologies of this issue, affecting the health of the population. Natural products have properties that contribute to health maintenance and health promotion, including reduction of the inflammatory process. Hancornia speciosa, popularly known as mangaba, is an abundant and native fruit in the Brazilian Cerrado, commercialized for culinary purposes and used because of its pharmacological properties. The objective of this study was to evaluate if the supplementation of different concentrations of mangaba pulp can improve intestinal motility and bowel health in Wistar rats. Forty male rats were divided into five groups. The experiment lasted 14 days and the groups were tested with water, industrialized laxative jelly made from tamarind as medication, or mangaba at 5, 10, and 15 mL/kg of body weight. Food intake, weight gain, ion balance, intestinal motility, and histopathological analysis of the small intestine, large intestine, and liver were evaluated. Supplementation of mangaba pulp at its highest concentration (15 mL/kg body weight) caused a 15% increase in the distance traveled by the charcoal meal, and a decrease in serum magnesium levels and white cells in both the small and large intestines. The results suggest that mangaba pulp presents laxative, anti-inflammatory properties and that its consumption is beneficial and should be encouraged.

Blockage of the P2X7 Receptor Attenuates Harmful Changes Produced by Ischemia and Reperfusion in the Myenteric Plexus.

INTRODUCTION: Our work analyzed the effects of a P2X7 receptor antagonist, Brilliant Blue G (BBG), on rat ileum myenteric plexus following ischemia and reperfusion (ISR) induced by 45 min of ileal artery occlusion with an atraumatic vascular clamp with 24 h (ISR 24-h group) or 14 d of reperfusion (ISR 14-d group). MATERIAL AND METHODS: Either BBG (50 mg/kg or 100 mg/kg, BBG50 or BBG100 groups) or saline (vehicle) was administered subcutaneously 1 h after ischemia in the ISR 24-h group or once daily for the 5 d after ischemia in the ISR 14-d group (n = 5 per group). We evaluated the neuronal density and profile area by examining the number of neutrophils in the intestinal layers, protein expression levels of the P2X7 receptor, intestinal motility and immunoreactivity for the P2X7 receptor, nitric oxide synthase, neurofilament-200, and choline acetyl transferase in myenteric neurons. RESULTS: The neuronal density and profile area were restored by BBG following ISR. The ischemic groups showed alterations in P2X7 receptor protein expression and the number of neutrophils in the intestine and decreased intestinal motility, all of which were recovered by BBG treatment. CONCLUSION: We concluded that ISR morphologically and functionally affected the intestine and that its effects were reversed by BBG treatment, suggesting the P2X7 receptor as a therapeutic target.

Antidiarrheal activity of α-terpineol in mice.

Diarrhea is one of the leading causes of infant death in the world accounting for high child mortality rate. It is also present in different pathophysiologies related to several etiological agents. The aim of this study is to investigate the antidiarrheal effect of α -Terpineol (α-TPN) in different diarrhea models in rodents. The antidiarrheal effect of α-TPN in the treatment of acute diarrhea and enteropooling induced by castor oil or PGE2 in Swiss mice pretreated orally with saline (NaCl 0.9%), Loperamide (5 mg/kg) and α-TPN (6.25, 12.5, 25 and 50 mg/kg) was analyzed. Additionally, parameters of severity, total weight of faeces and post-treatment for 4 h were evaluated. Modulation of the opioid and cholinergic pathways was performed and intestinal transit model using activated charcoal as marker was also used. The effect of α-TPN on secretory diarrhea was investigated using the model of fluid secretion in intestinal loops isolated from cholera toxin-treated mice. α-TPN showed antidiarrheal effect (*p < 0.05), reducing the total stool amount (*55%, *48%, *44%, *24%) and diarrheal (*47%, *66%; *56%, 10%) respectively for the doses tested. All doses investigated in the enteropooling test presented significant changes (*46%, *78%, *66%, *41% respectively) in relation to the control. α-TPN through the muscarinic pathway reduced the gastrointestinal transit (*31%), besides inhibiting PGE2-induced diarrhea (*39%). α-TPN also reduced fluid formation and loss of Cl- ions, by interacting directly with GM1 receptors and cholera toxin, thus increasing the uptake of intestinal fluids. The results suggest an anti-diarrheal activity of α-TPN due to its anticholinergic action, ability to block PGE2 and GM1 receptors and interaction with cholera toxin in secretory diarrhea, making it a promising candidate drug for the treatment of diarrheal diseases.

Antidiarrheal activity of a novel sulfated polysaccharide from the red seaweed Gracilaria cervicornis.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of marine seaweeds as a source of natural compounds with medicinal purposes is increasing in Western countries in the last decades, becoming an important alternative in the traditional medicine of many developing countries, where diarrhea still remains a severe public health problem, with high rates of mortality and morbidity. Sulfated polysaccharides (PLS) extracted from red seaweeds can exhibit therapeutic effects for the treatment of gastrointestinal disorders. Thus, the pharmacological properties of the PLS from Gracilaria cervicornis, an endemic seaweed found in the Brazilian northeast coast, was evaluated as an alternative natural medication for diarrhea. AIM OF THE STUDY: This study aimed to evaluate the antidiarrheal activity of sulfated polysaccharides (PLS) extracted from the red seaweed G. cervicornis in Swiss mice pre-treated with castor oil or cholera toxin. MATERIALS AND METHODS: The seaweed Gracilaria cervicornis was collected at Flecheiras beach (city of Trairí, State of Ceará, Brazil) and the PLS was obtained through enzymatic extraction and administered in mice (25-30 g) before diarrhea induction with castor oil or cholera toxin. For the evaluation of the total number of fecal output and diarrheal feces, the animals were placed in cages lined with adsorbent material. The evaluation of intestinal fluid accumulation (enteropooling) on castor oil-induced diarrhea in mice occurred by dissecting the small intestine and measuring its volume. The determination of Na+/K+-ATPase activity was measured in the small intestine supernatants by colorimetry, using commercial biochemistry kits. The gastrointestinal motility was evaluated utilizing an activated charcoal as a food tracer. The intestinal fluid secretion and chloride ion concentration were evaluated in intestinal closed loops in mice with cholera toxin-induced secretory diarrhea. The binding ability of PLS with GM1 and/or cholera toxin was evaluated by an Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The G. cervicornis PLS showed antidiarrheal effects in both acute and secretory diarrhea, reducing the total number of fecal output, diarrheic stools, intestinal fluid accumulation, and increasing small intestine Na+/K+-ATPase activity on castor oil-induced diarrhea. However, the PLS did not affect gastrointestinal motility, indicating that this compound has a different action mechanism than loperamide. In secretory diarrhea, the PLS decreased intestinal fluid secretion and small intestine chloride excretion, binding with GM1 and/or cholera toxin and blocking their attachment to the enterocyte cell surface. CONCLUSIONS: In conclusion, PLS has a significant antidiarrheal effect in acute and secretory diarrhea. Further investigation is needed towards its use as a natural medicine to treat diarrhea.

TNF-α inhibits SCF, ghrelin, and substance P expressions through the NF-κB pathway activation in interstitial cells of Cajal.

Ulcerative colitis is a chronic inflammatory disease of the colon where intestinal motility is disturbed. Interstitial cells of Cajal (ICC) are required to maintain normal intestinal motility. In the present study, we assessed the effect of tumor necrosis factor-alpha (TNF-α) on viability and apoptosis of ICC, as well as on the expression of stem cell factor (SCF), ghrelin, and substance P. ICC were derived from the small intestines of Swiss albino mice. Cell viability and apoptosis were measured using CCK-8 assay and flow cytometry, respectively. ELISA was used to measure the concentrations of IL-1ß, IL-6, ghrelin, substance P, and endothelin-1. Quantitative RT-PCR was used to measure the expression of SCF. Western blotting was used to measure the expression of apoptosis-related proteins, interleukins, SCF, and NF-κB signaling pathway proteins. TNF-α induced inflammatory injury in ICC by decreasing cell viability and increasing apoptosis and levels of IL-1ß and IL-6. TNF-α decreased the levels of SCF, ghrelin, and substance P, but had no effect on endothelin-1. TNF-α down-regulated expressions of SCF, ghrelin, and substance P by activating the NF-κB pathway in ICC. In conclusion, TNF-α down-regulated the expressions of SCF, ghrelin, and substance P via the activation of the NF-κB pathway in ICC.

Chewing Xylitol Gum could Accelerate Bowel motility Recovery after Elective Open Proctectomy for Rectal Cancer.

BACKGROUND: A number of studies with conflicting results have evaluated the effect of chewing gum on post-operative gastrointestinal recovery in patients after major colorectal surgery. OBJECTIVE: The objective of the study was to study the efficacy of chewing gum in patients with rectal cancer after elective open proctectomy only. METHODS: A randomized controlled clinical trial was performed. We recruited patients who would undergo elective open proctectomy for rectal cancer in Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital. Patients in the intervention arm received chewing gum 3 times a day postoperatively. All patients in the trial were placed on the same perioperative management and standardized post-operative care plans. The primary outcome was time to the first peristalsis sounds, time to first flatus and the first defecation. RESULTS: A total of 89 patients were recruited. The time to the first flatus was 42.33 ± 3.46 h in the gum group and 49.20 ± 1.42 h in the control group (p < 0.05). The time to the first defecation was significantly shorter in the gum-chewing group than in the control group (66.07 ± 2.36 vs. 78.37 ± 1.62 h; p < 0.05). Post-operative ileus (POI) was confirmed in 2 patients in the gum-chewing group and in 7 in the control group (7.0% vs. 23.9%; p = 0.028). DISCUSSION: The present study suggests that chewing gum is a method to reduce the time to first flatus, time to first defecation and POI in patients undergoing elective open proctectomy for rectal cancer.

Potential usefulness of methyl gallate in the treatment of experimental colitis.

Methyl gallate is a gallotannin widely distributed in nature. Previous studies have demonstrated its antioxidant, anti-inflammatory, antimicrobial and anti-tumor activities. In the present study, the activity of methyl gallate on experimental models of inflammatory bowel disease has been investigated. Experimental colitis was induced in Sprague-Dawley rats through the intracolonic instillation of an acetic acid solution (2 mL, 4% v/v). Methyl gallate (100 and 300 mg/kg, p.o.) and the reference drug mesalazine (100 mg/kg, p.o.) were tested. Methyl gallate induced a significant reduction in the colon weight/length ratio and macroscopic lesion score. Besides, the malondialdehyde content and the GSSG/GSH ratio were remarkably decreased. Furthermore, the administration of methyl gallate reduced the expression of COX2, IL-6, TNFα and the severity of microscopic tissue damage induced by acetic acid, while the mean goblet cell density was significantly higher in both the group treated with methyl gallate and the one treated with mesalazine, in comparison with untreated animals. The Na+K+ATPase pump activity was recovered in treated groups (control: 827.2 ± 59.6, colitis: 311.6 ± 54.8, methyl gallate 100 mg/kg: 642.2 ± 175.0, methyl gallate 300 mg/kg: 809.7 ± 100.6, mesalazine: 525.3 ± 81.7). Methyl gallate was also found to induce a significant reduction in the castor oil-induced intestinal motility in Swiss mice, decreasing the peristalsis by 74.5 and 58.82% at 100 and 300 mg/kg p.o., respectively. This compound also antagonized the jejunum contractions induced by Ach and CaCl2. This study demonstrates that methyl gallate exerts beneficial effects in a preclinical model of intestinal disorders.

TNF-α inhibits SCF, ghrelin, and substance P expressions through the NF-κB pathway activation in interstitial cells of Cajal

Ulcerative colitis is a chronic inflammatory disease of the colon where intestinal motility is disturbed. Interstitial cells of Cajal (ICC) are required to maintain normal intestinal motility. In the present study, we assessed the effect of tumor necrosis factor-alpha (TNF-α) on viability and apoptosis of ICC, as well as on the expression of stem cell factor (SCF), ghrelin, and substance P. ICC were derived from the small intestines of Swiss albino mice. Cell viability and apoptosis were measured using CCK-8 assay and flow cytometry, respectively. ELISA was used to measure the concentrations of IL-1β, IL-6, ghrelin, substance P, and endothelin-1. Quantitative RT-PCR was used to measure the expression of SCF. Western blotting was used to measure the expression of apoptosis-related proteins, interleukins, SCF, and NF-κB signaling pathway proteins. TNF-α induced inflammatory injury in ICC by decreasing cell viability and increasing apoptosis and levels of IL-1β and IL-6. TNF-α decreased the levels of SCF, ghrelin, and substance P, but had no effect on endothelin-1. TNF-α down-regulated expressions of SCF, ghrelin, and substance P by activating the NF-κB pathway in ICC. In conclusion, TNF-α down-regulated the expressions of SCF, ghrelin, and substance P via the activation of the NF-κB pathway in ICC.