Stool Weight Research Articles

Effectiveness of Propolis on Experimental Colitis Model In Rats

Aim: This study investigated the therapeutic potential of propolis in an experimental colitis model induced by acetic acid in female Wistar albino rats. Materials and Methods: Thirty rats were divided into five groups: a control group and four experimental groups. Colitis was induced in the second, third, and fifth groups by rectal administration of 1 ml of 4% acetic acid. The third group received rectal propolis solution (50 mg/ml), while the fourth group was given only rectal propolis solution. The fifth group received 1 ml of olive oil rectally after the onset of colitis. Stool consistency and weight loss were monitored, and colon tissue samples were collected for microscopic and macroscopic evaluation. The levels of MDA, MPO, and caspase-3 in tissue, as well as TNF-α and IL-10 levels in blood samples, were examined. Results: The group administered propolis showed a significant decrease in microscopic and macroscopic scores compared to the other experimental groups. The levels of MDA, MPO, and caspase-3 in the tissue, as well as TNF-α and IL-10 levels in blood samples, were significantly decreased in the propolis group compared to the other experimental groups. Weight loss and stool consistency also showed improvement in the propolis group compared to the other experimental groups. Discussion: Propolis may have therapeutic effects in experimental colitis induced by acetic acid. The decrease in oxidative damage and inflammation seen in the propolis group indicates that it may be a useful therapeutic agent for colitis treatment.

Golden Flower Tibetan Tea Polysaccharides Alleviate Constipation in Mice by Regulating Aquaporins-Mediated Water Transport System and Gut Microbiota.

Constipation, a widespread gastrointestinal disorder, often leads to the exploration of natural remedies. This study examines the efficacy of Golden Flower Tibetan Tea Polysaccharides (GFTTPs) in alleviating constipation in mice. Chemical analyses reveal that GFTTPs possess O-H, carboxyl, carboxylic acid (-COOH), and C-O-C groups, alongside a porous crystal structure with thermal stability. In animal experiments, GFTTPs significantly upregulated aquaporin 3 (AQP3) and aquaporin 8 (AQP8) expressions in the colon, enhancing water absorption and reducing fecal water content. At a 400 mg/kg dosage, GFTTPs notably improved colonic tissue alterations and serum levels of excitatory neurotransmitters caused by loperamide hydrochloride. They also beneficially altered gut microbiota, increasing Coprococcus, Lactobacillus, and Pediococcus populations. These changes correlated with improved stool frequency, consistency, and weight in constipated mice. Importantly, GFTTPs at 200 and 400 mg/kg doses exhibited comparable effects to the normal control group in key parameters, such as gastrointestinal transit rate and fecal moisture. These findings suggest that GFTTPs may serve as a potent natural remedy for constipation, offering significant therapeutic potential within the context of gut health and with promising implications for human applications.

Antioxidant Activities and Laxative Effect of Bioactive Compounds from Cynara cardunculus var. sylvestris

The present study aims to investigate the antioxidant and anti-constipation activities of the derived phenolic extracts in ribs wild cardoon (Cynara sylvestris). Analysed extracts (acetone, methanol and aqueous) exhibited high level of phenolic compounds and excellent antioxidant activities with significant IC50 values (p ≤0.05), as assessed by the DPPH radical-scavenging activity (0.84±0.08 - 2.44±0.007 μg/mL), ABTS cationic radical test (0.96 ±0.01- 136.67±6.75 μg/mL) and β-carotene bleaching assay (2.09±0.02-51.12±1.32 μg/mL). Also, higher levels of insoluble dietary fibers were found (56.18 ± 0.91% DW of neutral detergent fiber). The in vivo investigation was performed on Wistar rats to explore the ability of C. sylvestris aqueous extract (CSAE) in the enhancement of the gastrointestinal transit and the treatment of induced constipation by Loperamide (commercialized as Idium). A significant increase of 15, 24.5 and 32.4% in gastrointestinal motility was recordedwhen doses of CSAE increased (75, 150 and 300 mg/kg b.w, respectively). Food intake, water consumption, number and weight of stools were also increased in a dose-dependent manner, compared to the positive control (untreated). Moreover, CSAE provided significantly (p ≤0.05) and dose-dependently protection against oxidative stress by preserving normal antioxidant enzymes activities (SOD and GPx) in intestinal and colonic mucosa, and resorted hepatic enzymes (AST and ALT) and renal (urea and creatinine) levels to normal values. These results can be explained by the abundance of phenolic compounds and insoluble fibers in this plant. Therefore, its use can be encouraged in alimentary and pharmaceutical applications as antioxidant and laxative food supplements.

Budesonide Versus Mesalamine in Microscopic Colitis: A Comparative Meta-analysis of Randomized Controlled Trials.

Microscopic colitis (MC) is an inflammatory bowel disease of autoimmune origin that causes chronic watery diarrhea. Medications, including budesonide, mesalamine, loperamide, cholestyramine, and bismuth subsalicylate, are first-line therapies. Meanwhile, azathioprine, 6-mercaptopurine, and methotrexate are indicated for refractory MC. We aim to assess the efficacy and safety of budesonide compared with mesalamine for induction of remission in MC patients. We searched the Cochrane Library, Scopus, Web of Science, and PubMed for relevant clinical trials comparing either mesalamine or budesonide with a control group. We included the following outcomes: clinical remission (3 or fewer stools/day), daily stool weight, daily stool frequency, number of patients with clinical response <50% in the disease activity, and daily stool consistency. Safety end points included: any adverse event, serious adverse events, any adverse event-related discontinuation, abdominal discomfort, constipation, flatulence, nausea, dizziness, headache, bronchitis, nasopharyngitis, and depression. We conducted a meta-analysis model using the generic inverse variance method and performed a subgroup analysis based on the intervention administered. Nineteen randomized clinical trials were included. We found that after 6 weeks of follow-up, budesonide is associated with increased clinical remission rates compared with mesalamine [RR=2.46 (2.27, 2.67), and RR=2.24 (1.95, 2.57), respectively]. However, the test of subgroup difference revealed that the difference is not significant (P=0.25). After 8 weeks of follow-up, budesonide showed significantly higher clinical remission rates than mesalamine RR=2.29 (2.14, 2.45), and RR=1.7 (1.41, 2.05), respectively (P=0.003). Regarding the daily stool weight, patients in the budesonide group showed nonsignificant less stool weight [MD=-351.62 (-534.25, -168.99)] compared with mesalamine [MD=-104.3 (-372.34, 163.74)], P=0.14. However, daily stool frequency was significantly less in the budesonide group compared with mesalamine (P<0.001). Budesonide is associated with a significantly lower incidence of adverse events compared with mesalamine (P=0.002). Analysis of other safety endpoints was not significant between both groups. Budesonide was found to be better than mesalamine in MC patients in terms of clinical remission rate, especially after 8 weeks of follow-up. Budesonide also showed less incidence of adverse events. There is an urgent need for randomized, double-blinded clinical trials to provide direct and reliable evidence.

Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway.

Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation. To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism. Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression. HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, β-leucine (β-Leu) and traumatic acid, were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1. HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.

DIFFERENCES OF BIRTH WEIGHT AND ONSET OF ACHOLIC STOOL BETWEEN EXTRAHEPATIC AND INTRAHEPATIC CHOLESTASIS

Background: Biliary atresia (extrahepatic cholestasis) and neonatal hepatitis (intrahepatic cholestasis) are two main causes of cholestasis. It is important to distinguish the type of cholestasis for determine management. Patient with intrahepatic cholestasis have birth weight lower than extrahepatic cholestasis. Onset of acholic stool in extrahepatic cholestasis usually appear in 15-30 days of first life. The aim of the study to identify differences of birth weight and onset of acholic stool between the type of cholestasis. Method: A retrospective study on cholestasis children aged under 2 years was conducted at Dr. Soetomo General Academic Hospital from January 2012 to December 2016. A thorough history of birth weight and onset of acholic stool were undertaken. Based on histopatology liver biopsy patients were classified into twogroups: I (extrahepatic cholestasis) and II (intrahepatic cholestasis). Result: Statistical analysis of Mann Whitney U was used with p&lt;0.05 being significant. A total of 84 children were included, 55% were male. 40 children suffered from extrahepatic cholestasis (mean age 4.8 ± 2.6 months old) and 44 children suffered from intrahepatic cholestasis (mean age 2.9 ± SD 3.8 months old). The mean birth weight between extrahepatic and intrahepatic cholestasis were 2813 ± 704 gram vs 2717 ± 577 gram) (p=0.29). The mean onset of acholic stool between extrahepatic and intrahepatic cholestasis were 43.0 ± 60.6 days vs 26.6 ± 39.7 days (p=0.27). Conclusion : There is no difference of birth weight and onset of acholic stool between extrahepatic and intrahepatic cholestasis.

Pediatric Crohn's Disease in the Upper Gastrointestinal Tract: Clinical, Laboratory, Endoscopic, and Histopathological Analysis.

Crohn's disease (CD) is a progressive, multifactorial, immune-mediated disease characterized by chronic inflammation of any part of the gastrointestinal (GI) tract. Pediatric patients present with a more extensive form of the disease, especially in the upper GI tract with various histopathological inflammatory patterns. Our study aims to analyze the clinical, laboratory, endoscopic, and histopathological findings in children with diagnosed CD and compare results on the initial and follow-up tests. We have included 100 children and adolescents with CD, with performed endoscopic and histopathological (HP) procedures. The results of multiple biopsies executed in these 8 years were matched and compared. We found a statistically significant frequency reduction in stool changes (65.52% to 18.18%), weight loss (35.24% to 4%), and abdominal pain (41.86% to 6.67%) as presenting symptoms. There was an improvement in all laboratory values: fecal calprotectin (1000 to 60,8 μg/g), C-reactive protein (12.2 to 1.9 mg/L), and albumin (36 to 41 g/L). On esophagogastroduodenoscopy and ileo-colonoscopy 36.59% and 64.86% patients had specific findings, respectively. A total of 32 patients had evidence of Crohn's disease in the upper GI tract. Non-caseating granulomas were found on 9% of oesophageal, 18% of gastric, and 12% of duodenal biopsies. In the lower GI tract, we have observed a disease progression in the rectum (72.29 to 82.22%) and descending colon (73.49 to 80%). There was no registered disease progression in the upper GI tract. Our study demonstrated a significant decline in the frequency of symptoms and an improvement in laboratory values on the follow-up examinations. More than a third of our patients had specific endoscopic and HP findings in the upper GI tract, and an additional 23% had HP findings highly suggestive of CD. We demonstrated the importance of regular clinical, laboratory, endoscopic, and histopathological assessments of pediatric CD patients.

Protective effects of Moringa oleifera against acetic acid-induced colitis in rat: Inflammatory mediators’ inhibition and preservation the colon morphohistology

Moringa oleifera decoction is used in folk medicine to alleviate various gastrointestinal ailments and has been shown in several studies to exhibit diverse biological activities: antioxidant, anti-inflammatory, and myorelaxant on intestine strips. However, its protective effect on pro-inflammatory cytokines in colitis remains to be ascertained. We investigated Moringa oleifera leaf aqueous extract activities on a rat model of acetic acid-induced colitis. Thirty-six rats were divided in random into six groups, and received either distilled water (10 mL/kg), the aqueous leaf extract of Moringa oleifera (25, 50, and 100 mg/kg) or the reference drug Loperamide (5 mg/kg) for 20 days. Animal body weight and food intake were followed-up. Colitis was induced on day 15, and daily stool weight was followed up. Animals were sacrificed (day 21), serum concentrations of pro-inflammatory cytokines MPO, IL-6, and TNF-α were evaluated, and the colon and liver preserved for histological examinations. After one-week pre-treatment, a significant (P < 0.05) weight increase was observed. At day 20, the extract significantly (P < 0.01) prevented weight loss. Food intake decreased by 36.33% in the colitis control, and by 4.34% in the extract (100 mg/kg) treated animals (P < 0.01). Moringa oleifera (100 mg/kg, day 20) decreased stool weights to 4.75±0.3 g (P < 0.05). The extract decreased (P < 0.01) MPO level. At 100 mg/kg, it significantly (P < 0.05) reduced IL-6 –0.58 ± 0.14 against 0.85 ± 0.00 ng/L in the colitis control. At the same dose, TNF-α levels decreased to 417.96 ± 0.17 ng/L (P < 0.001). Moringa oleifera alleviated colitis symptoms by reducing stool emission, alleviating inflammation, and preserving colon and liver cytoarchitecture.

Intestinal Flora Imbalance Induced by Antibiotic Use in Rats.

This study aims to explore the effect of different doses of antibiotics on rats in order to observe alterations in their fecal microbiota, inflammatory changes in the colonic mucosa and four types of inflammatory markers in blood serum. Our methodology involved separating 84 female Sprague Dawley rats into groups A-G, with each group consisting of 12 rats. We collected the rat feces for analysis, using a distinct medium for bacterial cultivation and counting colonies under a microscope. On the 11th and 15th days of the experiment, half of the rats from each group were euthanized and 5 mL of abdominal aortic blood and colon tissues were collected. Inflammations changes of colon were observed and assessed by pathological Hematoxylin Eosin (HE) staining. Enzyme-linked immune sorbent assay (ELISA) was adopted for detecting C-reactive protein (CRP), IL-6, IL1-β and TNF-α. Our findings revealed that the initial average weight of the rats did not differ between groups (p>0.05); but significant differences were observed between stool samples, water intake, food intake and weight (p=0.009, <0.001, 0.016 and 0.04, respectively) within two hours after the experiment. Additionally, there were notable differences among the groups in nine tested microbiota before and after weighting methods (all p<0.001). There were no difference in nine microbiota at day 1 (all p>0.05); at day 4 A/B (p=0.044), A/D (p<0.001), A/E (p=0.029); at day 8, all p<0.01, at day 11, only A/F exist significant difference (p<0.001); at day 14 only A/D has difference (p=0.045). Inflammation changes of colon were observed between groups A-G at days 11 and 15. Significant differences between all groups can be observed for CRP, IL-6, IL1-β and TNF-α (p<0.001). This study suggests that antibiotics administration can disrupt the balance of bacteria in the rat gut ecosystem, resulting in an inflammatory response in their bloodstream and inducing inflammation changes of colon.

P164 MRT-6160, a VAV1-directed molecular glue degrader, inhibits disease progression and inflammation in a T-cell transfer model of Colitis

Abstract Background VAV1 is an immune-restricted guanine nucleotide exchange factor critical for T-cell receptor (TCR) and B-cell receptor (BCR) signalling. The role of VAV1 in T-cells has been demonstrated in knockout mice, which exhibit decreased effector functions and resistance to autoimmune disease models, and in CRISPR-based screens, where VAV1 has been highlighted as a top hit among positive regulators of T-cell function. Until now, VAV1 has remained undruggable by conventional small molecules. MRT-6160 is a first-in-class molecular glue degrader that specifically targets VAV1 for proteasomal degradation. Given the role of VAV1 in TCR and BCR signalling, MRT-6160-mediated degradation could be an effective therapeutic approach to treating autoimmune disease. Methods We first tested the impact of MRT-6160-mediated human (h)VAV1 degradation on primary human cells using in vitro stimulation-based assays. Oral bioavailability of MRT-6160 and in vivo degradation of murine (m)VAV1 was then examined in mice. We tested the efficacy of MRT-6160 using a T-cell adoptive transfer model of colitis treating recipients of pathogenic CD45RBhigh CD4+ T-cells (8 per group) with anti-TNF (25 mg/kg, Q3D) or MRT-6160 (1 mg/kg, QD) for 41 days following cell transfer. Disease activity index (DAI), comprising stool consistency and weight loss, was assessed every 3 days. At study termination, mesenteric lymph nodes (mLN) were profiled by flow cytometry and colon tissues were assessed for cytokine expression and histopathology. Results Degradation of hVAV1 by MRT-6160 inhibited T-cell activation, proliferation, and cytokine production in a dose-dependent manner. Orally administered MRT-6160 degraded mVAV1 and inhibited colitis disease progression by 85%, reducing average end point DAI scores more than a standard of care control (vehicle, p&amp;lt;0.0001; anti-TNF, p=0.0107). Compared to vehicle treated groups, MRT-6160 treated mice had fewer IL-17A+ (12.6 and 5.3% respectively) and TNF+ (37.6 and 17% respectively) CD4+ T cells in mLN tissue. Colon weight:length ratio was significantly reduced in MRT-6160-treated mice (42.5 mg/cm) compared to vehicle (70.3 mg/cm) and anti-TNF (61.2 mg/cm). Finally, pro-inflammatory cytokine expression in the colon mucosa was reduced in MRT-6160-treated mice compared to vehicle (IL-6: 1305.8 and 682.3 fg/mg; TNF: 175.5 and 66.9 ng/mg; respectively), as well as histopathological evidence of disease. Conclusion MRT-6160 demonstrates strong activity in a preclinical model of colitis reducing DAI, effector cytokine production, and colon tissue damage. These data suggest that MRT-6160-mediated degradation of VAV1 may have therapeutic benefit in IBD patients and warrants further clinical development.

Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice.

Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system. Calcium-sensing receptor (CaSR) inhibits both actions. The latter has been well documented in vitro but not in vivo. The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo. To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin (CTX) in mice. CTX was given orally to C57BL/6 mice to induce diarrhea. Calcium and calcimimetic R568 were used to activate CaSR. To maximize their local intestinal actions, calcium was administered luminally via oral rehydration solution (ORS), whereas R568 was applied serosally using an intraperitoneal route. To verify that their actions resulted from the intestine, effects were also examined on Cre-lox intestine-specific CaSR knockouts. Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl- or clinically by assessing stool consistency and weight loss. CTX induced secretory diarrhea, as evidenced by increases in fecal Cl-, stool consistency, and weight loss following CTX exposure, but did not alter CaSR, neither in content nor in function. Accordingly, calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines. Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts (villinCre/Casrflox/flox) and neuronal CaSR knockouts (nestinCre/Casrflox/flox). Treatment of acute secretory diarrheas remains a global challenge. Despite advances in diarrhea research, few have been made in the realm of diarrhea therapeutics. ORS therapy has remained the standard of care, although it does not halt the losses of intestinal fluid and ions caused by pathogens. There is no cost-effective therapeutic for diarrhea. This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.

Evaluating the Efficacy and Safety Profile of Good Morning™ Constipation Drops in a Loperamide-Induced Rat Model

Introduction: Constipation is a prevalent gastrointestinal condition globally, often managed with conventional laxatives that may cause side effects and dependency. Homeopathy, offering a holistic approach through diluted natural substances, aims to stimulate the body's self-healing mechanism. This study evaluates Good Morning™ drops, an innovative homeopathic formulation designed to safely and effectively manage constipation. Using a rat model of Loperamide-induced constipation, we evaluated its safety and efficacy, unveiling promising results.Materials and Methods: A rat model of Loperamide induced constipation was utilized to assess the efficacy and safety of Good Morning™ Constipation Drops. 3 unique formulations were prepared and employed to the animal model in 3 different doses. 72 rats were randomly assigned to 12 groups (3 control groups plus 3 formulations in 3 different doses totalling 9 groups), receiving specific variants or control treatments over the period of 21 days. Parameters including body weight, water intake, stool count, intestinal function, haematology, bleeding and clotting time, blood biochemistry, and organ weight were evaluated. Results and discussion: The results showed that all homeopathic formulations, particularly Variant 2, exhibited significant effects in Loperamide induced constipated rats. Across various parameters, Variant 2 consistently influenced food intake, stool characteristics, and small intestine motility. Safety assessments indicated overall well-being, withVariant 2 demonstrating superior survival outcomes. These findings position Variant 2 as a promising candidate for constipation management, emphasizing its consistent efficacy and safety in the rat model. Conclusion: In conclusion, Good Morning™ Constipation Drops exhibited a promising blend of safety, efficacy, and a multifaceted mechanism of action. The formulation, rich in botanical ingredients, demonstrates high safety with favorable survival rates. Efficacy is evident in improved stool counts, stool weights, Small Intestine Transition percentages, and impacts on lipid profiles and liver enzymes, highlighting its potential as a comprehensive solution for constipation relief.

Myrrh Essential Oil Improves DSS-Induced Colitis by Modulating the MAPK Signaling Pathway: In vitro and in vivo Studies.

To explore the mechanism and active components of the anti-colitis effects of myrrh essential oil (MEO). In this study, we investigated the anti-inflammatory effects and molecular mechanisms of MEO on dextran sulfate sodium (DSS)-induced colitis with in vitro cell experiments, RNA-seq (RNA Sequencing), Weighted gene co-expression network analysis (WGCNA), combined with "weighting coefficient" network pharmacology, as and in vivo pharmacodynamic experiments. A 3% DSS solution was used to induce colitis in BALB/c mice and MEO was administered orally. We performed gas chromatography-mass spectrometry (GC-MS) analysis of the MEO components. The disease activity index (DAI) was evaluated by observing body weight, fecal characteristics, and blood in the stool of mice. The levels of inflammatory cytokines (TNF-α and IL-1β) in mouse serum were measured using ELISA (Enzyme-linked immunosorbent assay) kits. Additionally, the expression of MAPK-related proteins (JNK, p-JNK, ERK, and p-ERK) in mouse colonic tissues was detected by Western blotting and immunohistochemistry. MEO (0.0625-0.125µg/g, p.o). significantly inhibited the expression of the inflammatory mediator Nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. After treatment, there was a significant increase in body weight and alleviation of diarrhea and bloody stools in colitis mice. It also reduced inflammatory cell infiltration. Furthermore, it decreased the serum levels of TNF-α and IL-1β, and reduced the activity of p-JNK and p-ERK in the MAPK pathway. MEO relieved DSS-induced colitis by modulating the MAPK pathway. The experimental results indicate that the MAPK pathway might be inhibited by the synergistic effect of gamma-Muurolene, Curzerene, beta-Elemene, and Furanoeudesma 1.3-diene in MEO, which provides a novel idea for subsequent research and development of new anti-colitis drugs.

Reducing the need for colonoscopy with adjusted FIT and FOBT for stool weight and serum Hb levels.

Reducing the need for colonoscopy with adjusted FIT and FOBT for stool weight and serum Hb levels.

Gastrointestinal Fermentable Polysaccharide Is Beneficial in Alleviating Loperamide-Induced Constipation in Mice.

To investigate the role of gastrointestinal (GI) polysaccharide fermentation in alleviating constipation, two polysaccharide fractions were isolated from a soluble fiber extract with determined anti-constipation activity: a 2.04 kDa neutral fraction (SSP-1) contained 99.29% glucose, and a 41.66 kDa acidic fraction (SSP-2) contained 63.85% uronic acid. After mice were given loperamide for 14 d to induce constipation, the GI transit rate increased significantly in the SSP-1 group (p < 0.05) but not in the SSP-2 group. The stool weight in the SSP-2 group was significantly higher than that in SSP-1 (383.60 mg vs. 226.23 mg) (p < 0.05). Both SSP-1 and SSP-2 groups had significantly increased serum gastrin and motilin levels (p < 0.05) and changes in their fecal short-chain fatty acid (SCFA) profiles, while SSP-1 showed better fermentation properties than SSP-2 in terms of statistically higher fecal contents of acetic acid and total SCFAs (p < 0.05). Bioinformatic analysis indicated that SSP-1 upregulated bacteria such as Oscillibacter to improve SCFA metabolism and stimulate GI hormone secretion, while SSP-2 had less influence on the gut microbiota. These results suggest that the neutral polysaccharide with superior GI fermentation properties exerted beneficial effects on constipation, while the less fermentable pectic fraction might act as a stool-bulking agent.

Effect of electroacupuncture on enteric neuronal autophagy in functional constipation mice.

To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower he-sea and front-mu points of large intestine based on enteric neuronal autophagy. A total of 40 SPF Kunming mice were randomly divided into 5 groups (n = 8), i.e. a control group, a model group, an acupuncture group, a 3-methyl adenine (3-MA) group, and a 3-MA + acupuncture group. Except the control group, the FC model was established by gavage with compound diphenoxylate suspension for 14 days in the other 4 groups. After successful modeling, the mice of the acupuncture group and the 3-MA + acupuncture group received EA at bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37), stimulated for 30 min with disperse-dense wave, 2 Hz/15 Hz of frequency, 1 mA of intensity. EA was delivered once daily. One course of treatment was composed of 5 days and 2 courses were needed, with an interval of 2 days. An intraperitoneal injection of 3-MA (15 mg/kg) was administered 30 min before EA in the mice of the 3-MA group and the 3-MA + acupuncture group, once daily. Before and after intervention, the time of the first black stool defecation and defecation behaviors in 6 h were observed in each group. After intervention, in every group, the small intestine propulsion rate was calculated, the colon tissue morphology was observed using HE staining, the ultrastructure of enteric neuronal autophagy was observed under transmission electron microscope, and the expressions of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1 and neuronal nuclear antigen protein (NeuN) in neurons of colonic muscularis were determined by immunohistochemistry. Before intervention, when compared with those in the control group, the time of the first black stool defecation was prolonged (P<0.01, P<0.05), and numbers (P<0.01), wet weight (P<0.01, P<0.05) and water content (P<0.05, P<0.01) of stool in 6 h were reduced in the model, acupuncture, 3-MA and 3-MA + acupuncture groups. After intervention, compared with those in the control group, the time of the first black stool defecation was longer (P<0.05), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were decreased in the model group. The time of the first black stool defecation was shortened (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were increased in the acupuncture group when compared with those in the model group. The time of the first black stool defecation was extended (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were declined in the 3-MA + acupuncture group in comparison with those in the acupuncture group. All layers of colon tissue were normal and intact in each group. When compared with the control group, the small intestine propulsion rate and the average optical density (OD) values of LC3, Beclin-1 and NeuN in neurons of colonic muscularis were decreased (P<0.01), and autophagosomes were dropped in the model group. In the acupuncture group, the small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis increased (P<0.01,P<0.05), and autophagosomes were elevated when compared with those in the model group. The small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis were dropped (P<0.05,P<0.01) in the 3-MA + acupuncture group in comparison with those in the acupuncture group. Electroacupuncture may promote enteric neuronal autophagy and increase the number of neurons so that the intestinal motility can be improved and constipation symptoms can be relieved in FC mice.

Constituent analysis, laxative activity, and toxicological evaluation of methanol extract of noni fruit (Morinda citrifolia L., Rubiaceae)

Noni fruits have gained considerable popularity as dietary supplements. However, the major constituents, the laxative activity, and the toxicity of Noni fruit remains still unknown. The purpose of the present study was, therefore, to analyze the constituents of methanol extract of Noni fruit by UPLC-MS, and further evaluate laxative activity and safety aspects of this Noni fruit-derived products in mice. UPLC-MS analysis identified eleven major constituents from this Noni fruit extract. Administration of this extract obviously shortened the time of first fecal excrement, significantly increased the total number and the weight of stools, and remarkably restored the intestinal transit to normal level in the constipated mice, with low toxicity to liver and kidney, and meanwhile, the abundance, composition, and function of gut microbiota remained homeostasis. These results revealed the laxative activity of the methanol extract of Noni fruit with low toxicity and no influence on gut microbiota.

Beyond Insoluble Dietary Fiber: Bioactive Compounds in Plant Foods.

Consumption of plant foods, including whole grains, vegetables, fruits, pulses, nuts, and seeds, is linked to improved health outcomes. Dietary fiber is a nutrient in plant foods that is associated with improved health outcomes, including a lower risk of chronic diseases such as cardiovascular disease, type 2 diabetes, and certain cancers. Different fibers deliver different health benefits based on their physiochemical properties (solubility, viscosity) and physiological effects (fermentability). Additionally, plant foods contain more than dietary fiber and are rich sources of bioactives, which also provide health benefits. The concept of the solubility of fiber was introduced in the 1970s as a method to explain physiological effects, an idea that is no longer accepted. Dividing total dietary fiber (TDF) into insoluble dietary fiber (IDF) and soluble dietary fiber (SDF) is an analytical distinction, and recent work finds that IDF intake is linked to a wide range of health benefits beyond increased stool weight. We have focused on the IDF content of plant foods and linked the concept of IDF to the bioactives in plant foods. Ancestral humans might have consumed as much as 100 g of dietary fiber daily, which also delivered bioactives that may be more important protective compounds in disease prevention. Isolating fibers to add to human diets may be of limited usefulness unless bioactives are included in the isolated fiber supplement.

Exploration of Anthelmintic, Blood Coagulant, Diuretic and Laxative Activities of Different Solvent Fractions of Flagellaria Indica Leaves

Flagellaria indica (Family: Flagellariaceae) is a common climbing plant found primarily in tropical regions of many countries. The plant has various traditional uses, although most of them lack scientific published reports. The crude ethanolic extract of F. indica leaves was fractionated based on polarity using water, ethyl acetate, and n-hexane. Biological screening was conducted on the anthelmintic, blood coagulation, diuretic, and laxative activities of the water, ethyl acetate, and n-hexane fractions of F. indica leaves. In the anthelmintic test, the n-hexane fraction showed a moderate effect with paralysis times of 16.79 and 13.62 minutes and death times of 27.34 and 21.81 minutes, respectively, at doses of 25 and 50 mg/mL.In the blood coagulant test, only the water fraction showed a notable effect. The clotting times were 4.33, 6.02, 7.68, and 8.32 minutes, respectively, at doses of 200, 100, 50, and 25 mg/mL. Diuretic activity was performed to determine the increase in the volume of excreted urine, and electrolyte analysis of urine was performed to determine pH, density, conductance, and Na+, Cl-, K+ levels, as well as natriuretic, kaliuretic, saluretic, and CAI indexes. The ethyl acetate fraction showed better diuretic activity than the n-hexane fraction, while the water fraction did not reveal a notable diuretic effect. The Na+, Cl-, K+, natriuretic, and saluretic indexes were found satisfactory in the ethyl acetate fraction, and the CAI index was better in the n-hexane fraction. In the laxative test, the n-hexane fraction showed the best laxative properties, with an increase in stool weight of 38% and 54% at doses of 250 and 500 mg/kg, respectively. These results suggest that different fractions of F. indica leaves contain distinct phytochemicals that may be responsible for these biological effects. The isolation of bioactive compounds could help justify its traditional uses in modern medicine.

PEG-4000 Ameliorates morphine-induced constipation in mice through inhibition of AQP-3 mRNA Expression

Morphine is μ-opioid receptor (MOR) agonist that is used clinically for patients suffering from moderate to severe pain. Morphine can cause constipation due to activation of μ-opioid receptors in the central nervous system and the nervous system in the gastrointestinal tract. It is caused by increasing the expression of AQP-3 in the instestine through increased of serotonin by enterochromaffin cells. PEG 4000 is one of the osmotic laxatives used to treat Opioid Induced Constipation (OIC). PEG 4000 affects the upregulation of serotonin re-uptake which can lead to expression enhancement of AQP-3. The purpose of this study was to analyze the effect of PEG 4000 on expression changes of aquaporin-3 in mice colon induced acute constipation with morphine.Constipation conditions and the effectiveness of laxative therapy are indicated by constipation parameters in the form of fecal water content and stool weight. This study used 36 male mice of the Balb/c line genus which were divided into 3 groups, normal saline, morphine, and morphine + PEG 4000. Each group was further divided into 2 subgroups based on the time of observation, namely the first hour and fifth hour after morphine induced. The expression of AQP-3 was observed using Polymerase Chain Reaction (PCR) method. The result of this study showed that the administration of PEG 4000 to mice induced constipation with morfine could decrease the expression of AQP-3 from (146,413±1,736) to (118,411±3,476) with p value &lt;0,05, increase the percentage of fecal water content from (0,000±0,000%) to (28,903±12,930%) with p value &lt;0,05 and increase the stool weight from (0,000±0,000g) to (0,928±0,178g) with p value &lt;0,01 From these results, it can be concluded that the administration of PEG 4000 in morphine induced constipation to mice was effective in reducing AQP-3 expression as well as increasing the percentage of fecal water content and stool weight.