Mucin Content Research Articles

Unique Novel Role of Adropin in a Gastric Ulcer in a Rotenone-Induced Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease, frequently associated with a gastric ulcer. We aimed to investigate the adropin neuroprotective/gastroprotective potential in the indomethacin (IND)-induced gastric ulcer in a rotenone-induced PD model. Rats were randomly divided into four groups: normal control group, rotenone/IND treated (PD /Ulcer) group, adropin treated PD/Ulcer group, and l-dopa/omeprazole (Om) treated PD/Ulcer group. There were ten rats selected for the normal control group. Striatal dopamine (DA), apoptosis/redox status, and motor/behavioral impairments were evaluated. Gastric oxidative stress, H+/K+-ATPase activity, prostaglandin E2, mucin content, and von Willebrand factor were measured. Gastric/striatal phosphatidylinositol 3-kinase (PI3K)/phosphorylated Akt and gastric vascular endothelial growth factor (VEGF)/striatal P53 immunoreactivities were checked. Striatal P53 upregulated modulator of apoptosis (Puma)/gastric vascular endothelial growth factor receptor-2 (Vegfr-2) expressions were evaluated. Adropin successfully restored striatal DA and attenuated rotenone-induced motor/behavior deficits along with strong gastroprotective potential, possibly through antioxidant activity via reduction in malondialdehyde level and upregulated superoxide dismutase, catalase activities, and serum ferric reducing antioxidant power. Adropin restored the delicate balance between the defective pro-survival PI3K/Akt/murine double minute 2 signals and apoptotic P53/Puma pathways. Adropin can be considered as a uniquely attractive therapeutic target in PD and its associated gastric ulcer.

The Lubricating Function of Mucin at the Gastroscope Device-Esophagus Interface

The mucous layer on the surface of human digestive tract is a dynamically balanced protective system, mainly containing mucin, enzymes, bicarbonate, epidermal growth factor and other protective factors. It has been found that mucins can protect epithelial cells from infection, dehydration, and physical, mechanical or chemical damage. There are a variety of disturbances that affect or destroy the function of the mucous layer, including mucus dysfunction and diseases of digestive tract. In this paper, the mechanical function of mucin on the surface of esophagus was studied using the UMT Tribometer with the porcine esophagus as the experiment sample. Trypsin was used to control the mucin content on the surface of esophagus. Results showed that the trypsin can affect the function of the mucin on the surface of esophagus. The friction coefficient and the relevant energy dissipation of trypsin-treated and non-trypsin-treated samples were significantly different. Due to the reduction of mucin on the esophageal surface by trypsin treatment, the friction coefficient and energy dissipation of the esophageal surface were significantly higher than that of the samples without trypsin treatment. During the friction test, the esophagus surface was severely damaged at both macro and micro scales after trypsin treatment, which indicated that the mucin can play a lubrication role at the gastroscope device-esophagus interface. The results can provide reference for clinical endoscopic examination and medical advice for clinical practice.

Estimation of lacrimal dysfunction indices in patients with recurrent pterygium

The rationale of the research is driven by the severity of dry eye syndrome (DES) in the pterygium recurrencies development as well as by the necessity to investigate tear dysfunction and methods for its optimal correction in this patient population.
 Purpose of the study. To assess the impact of tear dysfunction indices on the development of recurrent pterygium.
 Materials and methods. We observed 60 patients (67 eyes) with recurrent pterygium. Patients were divided into four observation groups depending on the number of recurrencies. In order to study the dynamics of the DES manifestations during the postoperative period, pathogenetic therapy was used, which included a tear fluid substitute. All patients underwent a comprehensive assessment of subjective and objective DES indices before and after surgery.
 Results. A positive dynamics of subjective manifestations and objective indices of DES under the action of a tear substitute after surgery was reliably confirmed. A decrease in the number of patients with type III and IV crystallization after surgery was confirmed. Conclusion. The obtained data indicate an increase in the mucin content in the tear fluid composition, which leads to a stabilization of the tear film and to a decrease in the DES intensity.

Changes of Human Gut Microbiome Correlated with Metabolomics After Cranberry Juice Consumption in a Double-Blinded, Placebo Controlled, Crossover Study

Abstract Objectives 1) To investigate the changes of gut microbiome after 3 days and 21 days of cranberry juice consumption; 2) to correlate changes of microbiome with metabolome. Methods A double blinded, placebo-controlled, cross-over intervention study were conducted in 17 healthy young women aged 18–29 with normal BMI. Fecal, urine, and plasma samples were collected at baseline, after 3 days, and after 21 days consumption of double strength cranberry juice or a placebo juice. DNA was extracted from fecal samples and 16s rRNA was sequenced. Discriminant metabolites in urine and plasma was analyzed by UHPLC-Q-Orbitrap-HRMS and 0 identified using OPLS-DA models. Results 21-days but not 3 days of cranberry juice consumption significantly increased alpha diversity of colon microbiome compared to baseline. Significant increase in the abundance of Firmicutes, Ruminococcaceae, Faecalibacterium, and F/B (Firmicutes to Bacteroidetes) ratios were found after 21-days of cranberry juice intake. This was accompanied by decreases in Bacteroidetes, Proteobacteria, Clostridia, Enterobacteriaceae, Veillonellaceae, Bacteroides, Parabacteroides, and Enterobacter. Gut microbial composition before and after 21-days of cranberry juice consumption was significantly per Bray-Curtis dissimilarity analysis. However, cranberry consumption did not alter fecal content of short chain fatty acids, ammonia, or mucin. Spearman's correlation analysis showed significant positive or negative correlations between selected strains of bacteria and discriminant metabolites. 4-O-methylgallic acid was a discriminant metabolite in urine after 21-days of cranberry juice consumption. Its content positively correlated with Parabacteroides but negatively correlated with Faecalibacterium (P < 0.05). 3-(Hydroxyphenyl) propionic acid was a discriminant metabolite in plasma after cranberry juice consumption. Its content negatively correlated with Enterobacteriaceae (P < 0.05). Conclusions 21-days but not 3 days of cranberry juice consumption significantly altered colon microbiome. Correlation between gut bacteria and plasma, urine metabolites suggested interaction between gut microbiome and serum and urine metabolome. Funding Sources This research is funded in part by Ocean Spray Cranberries, inc.

Aerosolized Toll-like Receptor Agonists Suppress Allergic Inflammation

Abstract Recent studies have linked exposure to microbes and a reduction of allergic diseases. We sought to determine whether activation of innate immunity by aerosolized Toll-like receptor (TLR) agonists could attenuate the development of allergic inflammation in mice. BALB/cJ mice were sensitized and challenged with House Dust Mite (HDM). Some mice were treated by aerosol with ligands for TLR9 (ODNm362) and TLR2/6 (Pam2CSK4) in combination (Pam2-ODN). Allergic inflammation was assessed by quantification of leukocytes in bronchoalveolar lavage fluid (BALF) and epithelial mucin content with periodic acid fluorescent Schiff stain (PAFS). Pam2-ODN-treated mice exhibited a 94% reduction in eosinophils, 90% reduction in lymphocytes, and a 44% reduction in epithelial mucin content. Lymphocyte subset analysis showed a 50% reduction in TH2 cells without a detectable change in any other TH subset. Using an alternate allergic inflammation model with Ovalbumin (OVA) Pam2-ODN-treated mice showed greater than 50% reductions in total and OVA-specific IgE serum concentrations. IgG2a concentrations, which are reduced in OVA-sensitized mice, returned to baseline with Pam2-ODN treatment. There is a stark contrast of the efficacy in mice treated before and after sensitization that suggests Pam2-ODN may modulate the tendency of sensitization when exposed to aeroallergens. Previous studies have shown that lung epithelial cells are required for Pam2-ODN lung responses, and taken together with these new data, Pam2-ODN may reprogram airway epithelial cells to be tolerogenic to aeroallergens, but additional investigation is required to understand the precise molecular mechanism of Pam2-ODN in this context.

Impact of Developmental Age, Necrotizing Enterocolitis Associated Stress, and Oral Therapeutic Intervention on Mucus Barrier Properties

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of incompletely understood pathophysiology predominantly affecting premature infants. While NEC is associated with microbial invasion of intestinal tissues, and mucus modulates interactions between microbes and underlying tissues, variations in mucus barrier properties with NEC-associated risk factors have not been investigated. This study explored differences in mucus composition (total protein, DNA, mucin content, sialic acid, and immunoregulatory proteins), as well as structural and transport properties, assessed by tracking of particles and bacteria (E. coli and E. cloacae) with developmental age and exposure to NEC stressors in Sprague Dawley rats. Early developmental age (5 day old) was characterized by a more permeable mucus layer relative to 21 day old pups, suggesting immaturity may contribute to exposure of the epithelium to microbes. Exposure to NEC stressors was associated with reduced mucus permeability, which may aid in survival. Feeding with breastmilk as opposed to formula reduces incidence of NEC. Thus, NEC-stressed (N-S) rat pups were orally dosed with breastmilk components lysozyme (N-S-LYS) or docosahexaenoic acid (N-S-DHA). N-S-LYS and N-S-DHA pups had a less permeable mucus barrier relative to N-S pups, which suggests the potential of these factors to strengthen the mucus barrier and thus protect against disease.

Alterations to Mucus Production and Secretion during Giardia Infection Involve Giardia Protease Activity and PAR2 Activation

BackgroundThe protozoan parasite Giardia duodenalis has been shown to disrupt the intestinal mucus barrier via unknown mechanisms, potentially disrupting host mucosal immunity and contributing to development of post‐infectious disorders. Protease‐activated receptor 2 (PAR2) has been identified as a potential target for secreted Giardia cysteine proteases, and may play a role in disruption of mucus production and secretion in the intestines.MethodsThe human colonic epithelial cell line LS174T was infected with Giardia trophozoites (isolates NF, WB, S2, and GSM). Prior to infection, trophozoites were treated with E64, a broad‐spectrum cysteine protease inhibitor, and LS174T were treated with a pepducin PAR2 antagonist, BAPTA, a calcium chelator, or U0126, an ERK1/2 inhibitor. MUC2 mucin gene expression was assessed using quantitative PCR (qPCR), and intracellular mucin content was quantified by staining with fluorescein‐coupled wheat germ agglutinin (WGA) and imaging using confocal microscopy.Chinese hamster ovary cells transfected with nano‐luciferase tagged PAR2 were incubated with Giardia trophozoites. Release of enzymes due to cleavage at the receptor N‐terminus by Giardia resulted in a luminescent signal proportional to the number of cleaved receptors.Wild type (WT) and PAR2 deficient (PAR2 −/−) mice were infected with Giardia trophozoites. The colonic mucus layer was stained using WGA and qPCR was performed for Muc2 and Muc5ac in the small and large intestines.ResultsGiardia NF, S2, and WB, but not GSM, upregulate MUC2 expression in LS174T cells. This increase was attenuated by inhibition of Giardia cysteine proteases and by antagonism of PAR2 or inhibition of calcium release or ERK1/2 signaling in LS174T cells. Preliminary results suggest that WGA staining is decreased upon exposure of LS174T to Giardia NF trophozoites.Giardia trophozoites cleaved PAR2 at the N‐terminus, suggesting they are capable of activating the receptor. The amount of cleavage was isolate‐dependent, reflecting differences in protease activity, and cleavage was significantly reduced by E64 treatment for all isolates.Giardia infected WT mice show increased Muc2 and Muc5ac expression in the colon, and increased Muc5ac but decreased Muc2 expression in the jejunum. These changes were not seen in PAR2−/− mice. Both WT infected and PAR2−/− non‐infected mice showed thinning of the colonic mucus layer compared to WT controls. There was some recovery in thickness in PAR2−/− infected mice.ConclusionsGiardia‐induced alterations to mucin gene expression in vitro and in vivo are dependent on PAR2 signaling. Giardia cysteine proteases cleave and activate PAR2, leading to both calcium release and MAPK pathway activation, which in turn contributes to altered gene transcription. Further, Giardia induces altered mucus secretion in vitro, which may contribute to thinning of the colonic mucus gel in vivo. Further study is required to determine the role of PAR2 in mucus secretion during Giardia infection.Support or Funding InformationCrohn’s Colitis Canada

Short-Term Fermented Soybeans with Bacillus amyloliquefaciens Potentiated Insulin Secretion Capacity and Improved Gut Microbiome Diversity and Intestinal Integrity To Alleviate Asian Type 2 Diabetic Symptoms

We determined that consuming chungkookjang fermented by Bacillus subtilis (BS) or Bacillus amyloliquefaciens (BA) alleviated hyperglycemia in partially pancreatectomized (Px) rats, an Asian type 2 diabetic (T2D) animal model. Px rats had deteriorated glucose metabolism with decreased glucose-stimulated insulin secretion and insulin sensitivity. Insulin secretion capacity was improved in the ascending order of the Px-control, positive control (3 mg of metformin/kg of body weight), BS (4.5% BS diet), BA (4.5% BA diet), and normal-control (sham-operated rats). BA and BS increased β-cell mass and decreased malondialdehyde contents and tumor necrosis factor α expression in the islets. BA increased hepatic peroxisome proliferator-activated receptor (PPAR)-α and PPAR-β similar to the positive control. Bacillales, Lactobacillales, and Verrucomicrobiales (Akkermensia muciniphila) increased and Enterobacteriales decreased in the BA and BS compared to the Px-control. BA prevented the decrease in the villi area and the number of goblet cells in intestinal tissues. In conclusion, BA improved glucose regulation by potentiating insulin secretion and reducing insulin resistance while maintaining gut mucin contents by improving gut microbiota in lean T2D rats.

A general overview of mucocele of appendix.

Mucocele of the appendix is a very rare disease entity that often discovered incidentally during surgery. It can result from both non-neoplastic and neoplastic lesions and histopathological examination is needed for confirmation. Failure to make an early preoperative diagnosis may results in its rapture and spillage of mucin contents into the peritoneal cavity leading to a disastrous complication of pseudomyxoma peritonei (PMP) that has a very bad prognosis. A clear pathological terminology and management strategies of appendiceal mucocele (AM) is lacking. This literature review aims to derive detailed information related to clinical significance of AM to avoid complication of PMP and plan appropriately during surgery according to the current evidence. The relevant articles from scientific databases such as Medline, PubMed, Google Scholar were searched and extracted using the keywords “mucocele appendix” “cystadenoma%”. Data based on epidemiology, clinical manifestations, complications, pathology, diagnostic work up and management were analyzed and summarized. A meticulous surgical excision is the mainstay of treatment and open surgical approach is still preferred over laparoscopy. Preoperative diagnosis of AM is very imperative as it may harbour neoplasm and can be made utilising the imaging tools like computed tomography and ultrasonography. Primary care physicians can have a crucial role in making early detection and timely referral for appropriate management in order to avoid complications. After appendectomy, 5-year survival rate for the simple AM is 91%-100% but it reduces to 25% for the malignant AM.

Morphometric analysis and mucin histochemistry of gallbladdersurface and glandular epithelium in swine

The aim of thestudy was to perform morphometric analysis and to distinguishhistochemically the variety of mucins in surface and glandular gallbladderepithelium in swine at different ages. The histochemical analyses by usingalcian blue staining at different pH and alcian blue-PAS technique alloweddistinguishing neutral and acidic mucin expression in the surface andglandular epithelium of gallbladder’s fundus, body and neck where age- andsite-specific localisation of mucin content was defined. Goblet cells alsoexpressed both neutral and acidic mucins. Morphometric analysis allowedestimating the height of the surface and glandular epithelium, diameter ofglands and crypts, and comparing these parameters between the three agegroups and three gallbladder parts. The goblet cells were observed in thegallbladder neck only. The morphometric and histochemical analyses extendthe knowledge on structural and topographic features of the studiedgallbladder components that could be useful as reference data for variety ofexperiments on this organ.

Multiple Mechanisms of Flaxseed: Effectiveness in Inflammatory Bowel Disease.

Materials and Methods Aqueous-methanolic crude extracts of Flaxseed (Fs.Cr) and Flaxseed oil were tested against 6% acetic acid- (AA-) induced colitis in BALB/c mice. Microscopic damage parameters of the hematoxylin and eosin-stained and periodic acid-Schiff-alcian blue-stained sections of the colon were scored to be assessed. Possible antispasmodic mechanism was studied on isolated rabbit jejunum, while antibacterial activity was assessed in vitro for microbes implicated in IBD. Results In AA-induced colitis, Flaxseed oil was found to be more effective in reducing mortality and colonic ulcers than Fs.Cr at 500 mg/kg dose. Fs.Cr was more efficacious in increasing mucin content as compared to oil, exhibiting slightly greater anti-inflammatory effect (50% vs 35%) and reducing depth of lesion (55% vs 42.31%, respectively). Antispasmodic activity of Fs.Cr (0.03 and 0.1 mg/ml) was mediated by phosphodiesterase inhibitors (PDEI, possibly PDE-4 subtype) with a resultant increase in cAMP levels. Flaxseed oil PDEI activity was mild (1 and 3 mg/ml). Fs.Cr (0.1 and 0.3 mg/ml) was potent in exhibiting anticholinergic activity, similar to dicyclomine, whereas Flaxseed oil showed anticholinergic effect at 1 and 3 mg/ml. Flaxseed oil (9 and 14 µg/ml) was bactericidal against enteropathogenic E.coli (EPEC), enterotoxigenic E.coli (ETEC), and enteroaggregative E.coli (EAEC), whereas Fs.Cr exhibited bactericidal effect against EPEC at 100 µg/ml. Conclusions Results of this study, taken together with previous studies, suggest that Flaxseed possesses anti-inflammatory, antibacterial, and antispasmodic action through multiple pathways and thus offers promising potential to be developed for IBD.

ANTIULCER ACTIVITY OF ELECTROHOMEOPATHIC DRUG (SPAGYRIC ESSENCE) CANCEROUS 15 - 3rd DILUTION AGAINST INDOMETHACIN-INDUCED GASTRIC ULCER IN RATS

Objective: To evaluate the curative protects activity of electrohomeopathic drug Cancerous15 (C15) against Indomethacin (IND)-induced gastric ulcer in albino rats. None of the data have been reported on antiulcer activity of C15 drug. Hence, the present study focuses on the scientific investigation of antiulcer activity of C15 against Indomethacin-induced peptic ulceration of rat models.
 Methods: A total number of 35 albino rats were divided into five groups equally. Pure water was given to Group 1 (normal). IND was given orally to Group 2 (ulcerated control). Cancerous15 third dilution was given to Group 3. IND was given to Group 4 and Group 5 animals, thereafter pretreatment with Esomeprazole (ESM) and C15-third dilution, respectively. The pretreatments were treated in each day’s interval for 21 days before IND administration. There was provision of food and water throughout the experimental period. On the 23rd day, the stomachs of the sacrificed rats were removed, and (1) ulcer index, (2) percentage of ulcer inhibition, (3) gastric volume, (4) pH, (5) pepsin activity, (6) mucin content, (7) malondialdehyde (MDA) concentration, and (8) stearidonic acid activity were studied.
 Results: The pre-treated animals with ESM and C15 shown as significantly decreases in ulcer index, gastric volume, pepsin activity and MDA concentration, and significant increase in the percentage ulcer inhibition, pH value, mucin content, and superoxide dismutase activity concentration in comparison to ulcer-induced rats.
 Conclusion: The study shows the significant ulcer protective activity of the C15 drug against IND-induced peptic ulceration in rats.

White Kidney Bean (Phaseolus Vulgaris L.) Consumption Reduces Fat Accumulation in a Polygenic Mouse Model of Obesity.

Clinical studies indicate that eating common bean, Phaseolus vulgaris L., plays a role in body weight regulation but mechanisms have yet to be elucidated. Here, we investigated the anti-obesogenic activity of white kidney bean in a mouse model of dietary-induced obesity. Bean consumption reduced the accumulation of adipose tissue in male and female C57BL6 mice. The anti-obesogenic effect of white kidney bean was not due to alterations in energy intake, energy excreted in the feces, or feed efficiency ratio. While bean consumption increased the mass of the intestine, no marked differences were consistently observed in crypt height, mucin content of goblet cells, proliferation index or zone of proliferation. However, significantly higher concentrations of total bacteria and of Akkermansia muciniphila were detected in cecal content of bean-fed mice, and the ratio of Firmicutes to Bacteroidetes was reduced. Bile acid content was higher in the ileum of bean-fed mice, but transcript levels of farnesoid X receptor were not significantly affected. Whether changes in bile-acid-mediated cell signaling play a role in bean-related differences in fat accumulation and/or overall metabolic health requires further investigation.

Protective Role of Casuarinin from Melaleuca leucadendra against Ethanol-Induced Gastric Ulcer in Rats.

Gastric ulcer is a major health problem. Current treatment options of gastric ulcer, including antagonists of histamine H2 receptor and inhibitors of the proton pump, do not cure gastric ulcers, but only provide temporary relief of symptoms and can be associated with severe side effects. The lack of effective and safe medications for this global health problem urges for the discovery of novel classes of compounds with potent activity and an acceptable safety profile. Ethanol-induced ulceration in rats was used to evaluate the gastroprotective activity of casuarinin, an ellagitannin isolated from Melaleuca leucadendra. Casuarinin (25, 50, and 100 mg/kg) reduced the ulcer area by 45, 78, and 99%, respectively, compared with the ulcer group. Casuarinin (100 mg/kg) increased mucin content by 1.8-fold and reduced acidity by 42%. At the same dose, it also increased the levels of reduced glutathione by 194%, catalase by 586%, and prostaglandin E2 to its normal level. In contrast, it attenuated the ethanol-increased levels of malondialdehyde by 56%, TNF-α by 58%, and caspase-3 by 87%. Histological findings demonstrated that casuarinin exhibited a protective effect against tissue alterations in response to the ethanol-induced ulcer. Casuarinin suppressed the immunoexpression of nuclear factor-kappa B, cyclooxygenase-2, and inducible nitric oxide synthase to their normal values. It also induced the expression of heat shock protein-70, reaching up to 4.9-fold in comparison with the ulcer group. The potent gastroprotective effect of casuarinin was thus attributed to its anti-inflammatory, antioxidant, and antiapoptotic effects. Our results suggest the potential application of casuarinin as an antiulcer agent from natural sources.

CORRELATIVE HISTOLOGICAL AND UMAMI TASTE ASSESSMENT STUDY OF GUSTATORY PAPILLAE ON THE DORSAL LINGUAL MUCOSA IN DIFFERENT ANIMAL SPECIES..

Background: A correlative characterization of oral mucosa was carried out in common animal species. Objective: This work aimed to correlate the histological structure of lingual gustatory papillae as well as the immunohistochemical reactivity to a particular umami receptor among different animal species to categorize the best experimental animal models for research. Methods: The dorsal lingual mucosal specimens were obtained from four species (orders) including; chicken (Galliformes), frogs (Anura), camels (Artiodactyla) and rabbits (Lagomorpha). They were processed for routine histological examination; histochemical staining using periodic acid Schiff (PAS) and Masson’s trichrome in addition to immunohistochemical localization of umami metabotropic glutamate receptor-4 (mGluR4) antibody. Results: Chicken, camels and rabbits exhibited keratinized stratified epithelium on the dorsal lingual mucosa with statistically greatest thickness in anterior lingual epithelium of chicken. For frogs, filiform and fungiform papillary walls were formed of mucous secreting columnar monolayer epithelium with a subjacent spindle cell layer. Insignificant differences in PAS staining intensity of dorsal lingual epithelium were noted between chicken anteriorly and rabbits as well as between chicken posteriorly and camels with the greatest significant intensity in frogs reflecting the highest content of glycogen and mucin. Likewise, the density of lamina propria and degree of collagen fibers bundling detected by Masson's trichrome were significantly different among species greatest in chicken and least in frogs. Intraepithelial taste buds were found in chicken while frogs displayed on top of fungiform papillae the largest gustatory disc among vertebrates. Camels and rabbits presented conventional papillary taste buds with the absence of foliate papillae in camels. Chicken and camel were negatively immunoreacted to mGluR4; frogs and rabbits were positively immunoreacted with the strongest reaction in rabbits. Conclusion: It was concluded that the direct association between histological variations of masticatory lingual mucosa and diverse environmental factors would reflect the adaptation capability of the lingual tissue.

Gastroprotective effects of Erythrina speciosa (Fabaceae) leaves cultivated in Egypt against ethanol-induced gastric ulcer in rats.

Members of the genus Erythrina have been traditionally used in the treatment of various ailments such as inflammation and gastrointestinal disorders. Erythrina speciosa (Fabaceae) is a spiny, deciduous shrub or small tree native to Southern America in Brazil. It is cultivated in Africa and Asia. The traditional usage of E. speciosa indicated its antibacterial, analgesic, and anti-inflammatory activities. Evaluation of the phytochemical constituents, gastroprotective effects and possible mechanism of action of the ethyl acetate fraction obtained from the methanol extract of E. speciosa leaves (ESLE). Chemical characterization of ESLE was done using high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). The gastroprotective activity of ESLE was evaluated using ethanol-induced gastric-ulcer model in rats. Rats were pre-treated with ESLE 25, 50 and 100 mg/kg 1 h before the administration of absolute ethanol. Histological analysis, mucin content, and total acidity were evaluated. The possible mechanism of action of ESLE was studied through the examination of oxidative stress and inflammatory markers, PGE2, and NF-κB, iNOS, COX-2, and HSP-70 immunoexpression. In vitro, anti-Helicobacter pylori activity of ESLE was also studied using micro-well dilution method. Fourteen compounds were tentatively identified including alkaloids, flavonoids, and saponins. ESLE exerted a powerful gastroprotective effect. The pre-treatment with ESLE at different doses resulted in a significant reduction in gastric lesions and significant elevation in the mucin production. These effects could be partially mediated by the potent anti-inflammatory activity of ESLE as evidenced by the significant reduction in the immunoexpression of NF-κB, COX-2, iNOS and the reduction in the pro-inflammatory marker, TNF-α. ESLE counteracted the ethanol-induced oxidative stress by increasing the levels of depleted GSH and catalase as well as significantly attenuating the ethanol-induced lipid peroxidation tissue levels. In addition, ESLE exhibited in vitro antibacterial activity against H. pylori. The chemical constituents of ESLE strongly support its potent gastroprotective effect suggesting its future potential application in the management of gastric ulcer by eliminating its symptoms and causes including H. pylori.

Chemical Modification of Cornstarch by Hydroxypropylation Enhances Cecal Fermentation‐Mediated Lipid Metabolism in Rats

AbstractHydroxypropylated (HP)‐cornstarch is fed to rats for 4 weeks and the effects on cecal fermentation and lipid metabolism are evaluated. In the cecum of rats fed either HP‐normal cornstarch (NCS) or HP‐waxy cornstarch (WCS), microbial composition is altered and the relative abundances of the Firmicutes and Bacteroidetes are decreased and increased, respectively, compared to high amylose cornstarch (HACS), NCS, and WCS groups. Cecal total‐short‐chain fatty acid (SCFA) content in the rats fed HP‐NCS and HP‐WCS is higher than the rats fed NCS and WCS. In HP‐NCS and HP‐WCS groups, cecal pH and mesenteric adipocyte area are decreased, and the plasma glucagon‐like peptide‐1 (GLP‐1) level and cecal mucin content are increased compared to HACS, NCS, and WCS groups. Plasma GLP‐1 level correlates positively with the cecal SCFA content and the serum insulin level, and negatively with the feed intake, while the adipocyte area positively correlates with the serum triglyceride level. Therefore, HP‐cornstarch may have possessed beneficial traits that enhance cecal fermentation and thereby influenced lipid metabolism, equally or greater than that of HACS.

GASTROPROTECTIVE ACTIVITY OF SESAME (SESAMUM INDICUM) SEEDS EXTRACT IN ALENDRONATE-INDUCED GASTRIC ULCER IN RATS

Objectives: Bisphosphonates are known to cause gastritis and only few studies have evaluated the use of plant extracts in the treatment of bisphosphonate induced peptic ulcers. In the present study, we examined the effect of sesame seed extract in the alendronate-induced gastric ulcer in adult Wistar rats.
 Methods: Thirty adult Wistar rats (180–250 g) of both sexes, divided into five groups (n=6) were used: Group 1 (vehicle control) – 0.9% saline, Group 2 (ulcer control) – alendronate 60 mg/kg, Group 3 (standard) – alendronate 60 mg/kg + pantoprazole 30 mg/kg/day, Group 4 (test groups) – alendronate 60 mg/kg + sesame 0.5 mg/kg, and Group 5 (test groups) – alendronate 60 mg/kg + sesame 1 mg/kg. All drugs were given orally once daily for 7 days except for alendronate given only on day 1. On day 8, rats were sacrificed, and stomach tissues were analyzed macroscopically for ulcers. Estimation of gastric pH, acidity, and volume was done along with mucin content measurement. One-way ANOVA followed by Tukey’s post hoc test was used for statistical analysis with p<0.05 taken as significant.
 Results: Our study found that sesame extract given therapeutically at doses of 0.5 and 1 mg/kg showed comparable results with that of pantoprazole 30 mg/kg. Both the doses of sesame, 0.5 and 1 mg/kg showed similar gastroprotective activity against alendronate-induced gastric ulcers in Wistar rats.
 Conclusion: The findings of this study clearly demonstrated the protective effects of Sesame against alendronate-induced gastric ulceration.

In vivo antiulcer activity, phytochemical exploration, and molecular modelling of the polyphenolic-rich fraction of Crepis sancta extract.

Bioactivity-guided investigation of the methanol extract of Crepis sancta aerial parts, collected off Al-Tafilah, South Jordan, was applied, and in this study, the extract was explored for its phytochemical components and in vivo antiulcer activity. In addition, a docking study involving the purified compounds with the newly crystalized gastric proton pump (PDB # 5YLU) was performed. In-depth phytochemical investigation using the state-of-the-art chromatographic and analytical techniques was implemented resulting in the identification of two eudesmane-type sesquiterpenoids, 3-oxo-γ-costic acid (1) and its methyl ester (2) together with seven different methoxylated flavonols (3-9) as the extract's major components. The in vivo antiulcer study at three different doses (50, 100, and 200mg/kg) against ethanol-induced gastric ulcer in male albino rats, compared to omeprazole (20mg/kg) as a standard proton pump inhibitor antiulcer drug, revealed that the tested extract, at the middle and the highest doses, featured comparable or even superior activities relative to omeprazole as deduced from histopathological examination, in particular with regardto reducing inflammatory cell infiltration and ceasing mucosal haemorrhage. The tested extract revealed also a dose-dependent reduction in the volume and titrable acidity of the gastric juice together with a dose-dependent increase in the protective gastric mucin content which may explain the noticeable gastroprotective effect. Molecular modelling study of the isolated compounds showed a binding mode similar to the co-crystallized substrate vonoprazan in 5YLU which strengthens the importance of the tested extract as a potential natural remedy for treating gastric ulcer.

Gastroprotective effect of cilostazol against ethanol- and pylorus ligation-induced gastric lesions in rats.

Despite the availability of effective antiulcer medications, their suboptimal safety profile ignites the search for alternative/complementary treatments. Drug repositioning is an attractive, efficient, and low-risk strategy. Cilostazol, a clinically used phosphodiesterase 3 inhibitor, has pronounced anti-inflammatory and vasodilatory effects suggesting antiulcer activity. Using ethanol-induced and pyloric ligation-induced gastric ulcer models, we investigated the gastroprotective effect of cilostazol (5 or 10mg/kg, p.o.) in comparison with the standard antiulcer ranitidine (50mg/kg, p.o.) in rats. Gastric mucosa was examined macroscopically, histologically, and biochemically for ulcer severity, markers of oxidative stress, proinflammatory cytokines, apoptotic, and cytoprotective mediators. Gastric acidic output, peptic activity, and mucin content were measured in gastric fluids. Pretreatment with cilostazol reduced ulcer number and severity, ameliorated redox status (reduced glutathione and malonaldehyde content), and decreased levels of IL-1β, IL-6, and TNF-훼 in gastric mucosa, in parallel with increases in mucosal defensive factors nitric oxide (NO), prostaglandin E2 (PGE2), and heat-shock protein 70 (HSP70) promoting mucus secretion, tissue perfusion, and regeneration. Histological examination confirmed the beneficial effects of cilostazol in terms of reducing focal necrosis and infiltration of inflammatory cells, as well as increasing mucopolysaccharide content. These beneficial effects are likely secondary to an increase in cAMP and decrease in apoptosis regulator Bcl-2-associated X protein (BAX). Cilostazol, in a dose-dependent effect, exhibited vasodilatory, anti-inflammatory, and antiapoptotic actions in the gastric mucosa resulting in significant antiulcer activity comparable with the standard drug, ranitidine, but devoid of antisecretory activity. Therefore, its use should be dose and ulcer-inducer dependent.