Medicinal plants of Moraceae family have been well-recognized traditionally due to their versatile applications in various fields including agriculture,cosmetic and food as well as in pharmaceutical industries. Their biomedical and medicinal importance is reflected from their broad range of pharmacological activities for treatment of various inflammatory conditions,cancer,infectious diseases,and gastrointestinal disorders.The present review was aimed to summarize and critically discuss the biomedical implications of Morus species,their bioactive compounds,and phytochemicals.Bioactivity guided fractionation of these medicinal plants revealed that different types of bioactive phytochemicals and secondary metabolites such as steroids, saponins, alkaloids, glycosides and phenolic compounds including terpenoids,flavonoids,anthocyanins and tannins were present.The critical analysis of the literature revealed that the aqueous,methanolic,and ethanolic ex-tracts of Morus species and their bioactive compounds exhibit remarkable anti-oxidative, anti-diabetic, anti-stress, nephroprotective, antimicrobial, anti-mutagenic, anticancer, anxiolytic, hepatoprotective, anthelmintic, antimicrobial, immune-modulatory and cholesterol lowering effects.Based on the literature review and bioactivity guided inves-tigation of Morus species and their phytomedicinal effects,we anticipate that these herbal products hold excellent potential for future research.

Post-operative ileus (POI) is the transient cessation of coordinated gastrointestinal motility after abdominal surgical intervention. It decreases quality of life, prolongs length of hospital stay, and increases socioeconomic costs. The mechanism of POI is complex and multifactorial, and has been broadly categorized into neurogenic and inflammatory phase. Neurogenic phase mediated release of corticotropin-releasing factor (CRF) plays a central role in neuroinflammation, and affects both central autonomic response as well hypothalamic-pituitary-adrenal (HPA) axis. HPA-stress axis associated cortisol release adversely affects gut microbiota and permeability. Peripheral CRF ( p CRF) is a key player in stress induced gastric emptying and colonic transit. It functions as a local effector and interacts with the CRF receptors on the mast cell to release chemical mediators of inflammation. Mast cells proteases disrupt epithelial barrier via protease activated receptor-2 (PAR-2). PAR-2 facilitates cytoskeleton contraction to reorient tight junction proteins such as occludin, claudins, junctional adhesion molecule, and zonula occludens-1 to open epithelial barrier junctions. Barrier opening affects the selectivity, and hence permeation of luminal antigens and solutes in the gastrointestinal tract. Translocation of luminal antigens perturbs mucosal immune system to further exacerbate inflammation. Stress induced dysbiosis and decrease in production of short chain fatty acids add to the inflammatory response and barrier disintegration. This review discusses potential mechanisms and factors involved in the pathophysiology of POI with special reference to inflammation and interlinked events such as epithelial barrier dysfunction and dysbiosis. Based on this review, we recommend CRF, mast cells, macrophages, and microbiota could be targeted concurrently for efficient POI management.

Poultry farming not only provides high nutritious food but also creates employment opportunity for rural masses. Documented evidences elaborates that helminth parasitism is most deciduous problem of chickens especially in developing world. Ascaridia (A.) galli, a nematode of small intestine, has been considered as the most common and important parasite of chicken. The present study was carried out to investigate prevalence and severity of A. galli in White Leghorn layers (housing type: battery cage and deep litter, 50 each) and Fayoumi-Rhode Island Red crossbred (male and female: 50 each) flock rearing at Government Poultry Farm, Dina, Punjab, Pakistan. Two hundred faecal samples were examined by using standard parasitological and McMaster egg counting technique. The overall prevalence was 24.5% at farm, 13% in White leghorn layer (battery cage=2%, deep litter=24%) and 36% in Fayoumi-Rhode Island Red (male=34%, female=38%). It was also observed that White leghorn layer rearing in deep litter had more severe infection (EPG=1920) of A. galli compare with battery cages birds (EPG=500). Parasite prevalence was significantly related with sex (P<0.05) in Fayoumi-Rhode Island Red and male birds had less number of average parasites (0.34±0.47) as compared to females (0.38±0.490). Additionally, female birds were under serious threat of infection (EPG=2270) compared with its counterpart (EPG=1250). Given the high infection rates, particular attention should be paid to management and provision of feed supplement to White leghorn layer housing in deep litter and female bird of Fayoumi-Rhode Island Red crossbred.

Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common gastrointestinal (GI) diseases; however, there is frequent overlap between FD and IBS patients. Emerging evidence links the activation of corticotropin releasing factor (CRF) receptors with stress-related alterations of gastric and colonic motor function. Therefore, we investigated the effect of peripheral CRF peptide and water avoidance stress (WAS) on upper and lower GI transit in guinea pigs. Dosages 1, 3, and 10 µg/kg of CRF were injected intraperitoneally (IP) in fasted guinea pigs 30 minutes prior to the intragastric administration of charcoal mix to measure upper GI transit. Colonic transits in non-fasted guinea pigs were assessed by fecal pellet output assay after above IP CRF doses. Blockade of CRF receptors by Astressin, and its effect on GI transit was also analyzed. Guinea pigs were subjected to WAS to measure gastrocolonic transit in different sets of experiments. Dose 10 µg/kg of CRF significantly inhibited upper GI transit. In contrast, there was dose dependent acceleration of the colonic transit. Remarkably, pretreatment of astressin significantly reverses the effect of CRF peptide on GI transit. WAS significantly increase colonic transit, but failed to accelerate upper GI transit. Peripheral CRF peptide significantly suppressed upper GI transit and accelerated colon transit, while central CRF involved WAS stimulated only colonic transit. Therefore, peripheral CRF could be utilized to establish the animal model of overlap syndrome.
Acceleration ; Animals ; Charcoal ; Colon* ; Corticotropin-Releasing Hormone ; Dyspepsia ; Guinea Pigs* ; Guinea* ; Humans ; Irritable Bowel Syndrome ; Models, Animal ; Receptors, Corticotropin-Releasing Hormone ; Water*

BACKGROUND/AIMS: Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. METHODS: The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. RESULTS: DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. CONCLUSIONS: DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.
Analgesics, Opioid ; Animals ; Baths ; Charcoal ; Colon ; Corydalis ; Gastrointestinal Transit ; Guinea Pigs* ; Guinea* ; Ileum ; Morphine ; Muscle Contraction ; Muscles ; Semen

BACKGROUND/AIMS: Postoperative ileus (POI) is characterized by impaired propulsive function of the gastrointestinal tract after surgery. Although inflammation is considered to be an important pathogenesis of POI, significant data are lacking. We aim to correlate the recovery time of postoperative dysmotility with that of inflammation and mucosal permeability. METHODS: An experimental POI model of guinea pig was used. Contractile activity of the circular muscle of the stomach, jejunum, ileum, and proximal colon was measured through a tissue bath study. Inflammatory cells were counted, and the expression of calprotectin and tryptase were analyzed. The expression of protease-activated receptor 2 (PAR-2), claudin-1, and claudin-2 were analyzed with immunofluorescence. RESULTS: The small bowel and colon showed decreased contractile amplitude in the POI groups compared to control. In contrast to the colon, the contractile amplitude of the small bowel significantly recovered in the POI group at 6 hours after the operation compared to the control group. Inflammation was highly significant in the POI groups compared to the control and sham groups, especially in the colon. Immunofluorescence showed increased PAR-2 expression in the POI groups compared to sham. The decreased claudin-1 expression and increased claudin-2 expression may suggest increased mucosal permeability of the small bowel and colon in the POI groups. CONCLUSIONS: Increased inflammation and mucosal permeability may play an important role in the differential recovery stages in POI. These data may provide further insights into the pathophysiology and potential new therapeutic prospects of POI.
Animals ; Baths ; Claudin-1 ; Claudin-2 ; Colon ; Fluorescent Antibody Technique ; Gastrointestinal Tract ; Guinea Pigs ; Guinea ; Ileum ; Ileus ; Inflammation ; Jejunum ; Leukocyte L1 Antigen Complex ; Permeability ; Receptor, PAR-2 ; Stomach ; Tryptases

BACKGROUND/AIMS: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common gastrointestinal (GI) disorders and these patients frequently overlap. Trimebutine has been known to be effective in controlling FD co-existing diarrhea-dominant IBS, however its effect on overlap syndrome (OS) patients has not been reported. Therefore, we investigated the effect of trimebutine on the model of OS in guinea pigs. METHODS: Male guinea pigs were used to evaluate the effects of trimebutine in corticotropin-releasing factor (CRF) induced OS model. Different doses (3, 10, and 30 mg/kg) of trimebutine were administered orally and incubated for 1 hour. The next treatment of 10 μg/kg of CRF was intraperitoneally injected and stabilized for 30 minutes. Subsequently, intragastric 3 mL charcoal mix was administered, incubated for 10 minutes and the upper GI transit analyzed. Colonic transits were assessed after the same order and concentrations of trimebutine and CRF treatment by fecal pellet output assay. RESULTS: Different concentrations (1, 3, and 10 μg/kg) of rat/human CRF peptides was tested to establish the OS model in guinea pigs. CRF 10 μg/kg was the most effective dose in the experimental OS model of guinea pigs. Trimebutine (3, 10, and 30 mg/kg) treatment significantly reversed the upper and lower GI transit of CRF induced OS model. Trimebutine significantly increased upper GI transit while it reduced fecal pellet output in the CRF induced OS model. CONCLUSIONS: Trimebutine has been demonstrated to be effective on both upper and lower GI motor function in peripheral CRF induced OS model. Therefore, trimebutine might be an effective drug for the treatment of OS between FD and IBS patients.
Animals ; Charcoal ; Colon ; Corticotropin-Releasing Hormone ; Dyspepsia ; Guinea Pigs ; Guinea ; Humans ; Irritable Bowel Syndrome ; Male ; Peptides ; Trimebutine

Background/Aims: The aim of this study is to identify the alteration in intestinal permeability with regard to the development of post-operative ileus (POI).Moreover, we investigated drug repositioning in the treatment of POI. Methods: An experimental POI model was developed using guinea pigs. To measure intestinal permeability, harvested intestinal membranes of the ileum and proximal colon was used in an Ussing chamber. To identify the mechanisms associated with altered permeability, we measured leukocyte count and expression of calprotectin, claudin-1, claudin-2, and mast cell tryptase. We compared control, POI, and drug groups (mosapride [0.3 mg/kg and 1 mg/kg, orally], glutamine [500 mg/kg, orally], or ketotifen [1 mg/kg, orally] with regard to these parameters. Results: Increased permeability after surgery significantly decreased after administration of mosapride, glutamine, or ketotifen. Leukocyte counts increased in the POI group and decreased significantly after administration of mosapride (0.3 mg/kg) in the ileum, and mosapride (0.3 mg/kg and 1 mg/kg), glutamine, or ketotifen in the proximal colon. Increased expression of calprotectin after surgery decreased after administration of mosapride (0.3 mg/kg), glutamine, or ketotifen in the ileum and proximal colon, and mosapride (1 mg/kg) in the ileum. The expression of claudin-1 decreased significantly and that of claudin-2 increased after operation. After administration of glutamine, the expression of both proteins was restored. Finally, mast cell tryptase levels increased in the POI group and decreased significantly after administration of ketotifen. Conclusions The alteration in intestinal permeability is one of the factors involved in the pathogenesis of POI. We repositioned 3 drugs (mosapride, glutamine, and ketotifen) as novel therapeutic agents for POI.

Background/Aims: The aim of this study is to identify the alteration in intestinal permeability with regard to the development of post-operative ileus (POI).Moreover, we investigated drug repositioning in the treatment of POI. Methods: An experimental POI model was developed using guinea pigs. To measure intestinal permeability, harvested intestinal membranes of the ileum and proximal colon was used in an Ussing chamber. To identify the mechanisms associated with altered permeability, we measured leukocyte count and expression of calprotectin, claudin-1, claudin-2, and mast cell tryptase. We compared control, POI, and drug groups (mosapride [0.3 mg/kg and 1 mg/kg, orally], glutamine [500 mg/kg, orally], or ketotifen [1 mg/kg, orally] with regard to these parameters. Results: Increased permeability after surgery significantly decreased after administration of mosapride, glutamine, or ketotifen. Leukocyte counts increased in the POI group and decreased significantly after administration of mosapride (0.3 mg/kg) in the ileum, and mosapride (0.3 mg/kg and 1 mg/kg), glutamine, or ketotifen in the proximal colon. Increased expression of calprotectin after surgery decreased after administration of mosapride (0.3 mg/kg), glutamine, or ketotifen in the ileum and proximal colon, and mosapride (1 mg/kg) in the ileum. The expression of claudin-1 decreased significantly and that of claudin-2 increased after operation. After administration of glutamine, the expression of both proteins was restored. Finally, mast cell tryptase levels increased in the POI group and decreased significantly after administration of ketotifen. Conclusions The alteration in intestinal permeability is one of the factors involved in the pathogenesis of POI. We repositioned 3 drugs (mosapride, glutamine, and ketotifen) as novel therapeutic agents for POI.

Background/Aims: Achalasia is an esophageal motility disorder characterized by dysphagia and noncardiac chest pain. Impairment of vagal function has been reported in achalasia. This study evaluated autonomic nervous system (ANS) dysfunctions in patients with achalasia to establish a correlation between an ANS dysfunction and the clinical symptoms of achalasia. Methods: Nineteen patients with achalasia (six males/13 females; mean age, 47.1±16.3 years) and 10 healthy controls (four males/six females; 34.8±10.7 years) were enrolled prospectively at Gangnam Severance Hospital between June 2013 and June 2014. All patients completed a questionnaire on ANS dysfunction symptoms and underwent a heart rate variability (HRV) test. Results: ANS dysfunction symptoms were present in 13 patients with achalasia (69%) and three controls (30%). The ANS dysfunction score was significantly higher in patients with achalasia than in the controls (p=0.035). There were no significant differences in the standard deviation of all normal R-R intervals, high frequency (HF), low frequency (LF), and LF/HF ratio in the HRV test. In subgroup analysis comparing female achalasia patients with controls, the cardiac activity was significantly higher in the female achalasia patients than in the controls (p=0.036). The cardiac activity (p=0.004) and endurance to stress (p=0.004) were significantly higher in the achalasia patients with ANS dysfunction symptoms than the achalasia patients without ANS dysfunction symptoms. Conclusions ANS dysfunction symptoms are common in patients with achalasia. Female achalasia patients and those with ANS dysfunction symptoms showed increased cardiac activity. Hence, more attention should be paid to cardiac overload in achalasia patients who are female or have ANS dysfunction symptoms.