Fecal Weight Research Articles

Screening the effective components in treating dampness stagnancy due to spleen deficiency syndrome and elucidating the potential mechanism of Poria water extract.

Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer. However, the specific effective components and the potential mechanism of Poria remain largely unknown. To identify the effective components and the mechanism of Poria water extract (PWE) to treat dampness stagnancy due to spleen deficiency syndrome (DSSD), a rat model of DSSD was established through weight-loaded forced swimming, intragastric ice-water stimulation, humid living environment, and alternate-day fasting for 21 days. After 14 days of treatment with PWE, the results indicated that PWE increased fecal moisture percentage, urine output, D-xylose level and weight; amylase, albumin, and total protein levels; and the swimming time of rats with DSSD to different extents. Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS. Mechanistic studies revealed that PWE significantly increased the expression of serum motilin (MTL), gastrin (GAS), ADCY5/6, p-PKAα/β/γ cat, and phosphorylated cAMP-response element binding protein in the stomach, and AQP3 expression in the colon. Moreover, it decreased the levels of serum ADH, the expression of AQP3 and AQP4 in the stomach, AQP1 and AQP3 in the duodenum, and AQP4 in the colon. PWE induced diuresis to drain dampness in rats with DSSD. Eleven main effective components were identified in PWE. They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach, MTL and GAS levels in the serum, AQP1 and AQP3 expression in the duodenum, and AQP3 and AQP4 expression in the colon.

P546 Comparative efficacy and safety of upadacitinib versus ustekinumab as induction therapy in patients with moderately to severely active ulcerative colitis: A matching-adjusted indirect comparison

Abstract Background Upadacitinib (UPA), an oral Janus kinase inhibitor, and ustekinumab (UST), a parenteral IL-12/23 inhibitor, are approved therapies for patients (pts) with moderately to severely active Ulcerative Colitis (UC). In the absence of head-to-head data, we conducted a placebo (PBO)-anchored matching-adjusted indirect comparison (MAIC) to compare efficacy and safety of UPA vs UST during induction. Methods Pts received UPA 45 mg oral, once daily for 8 weeks or PBO in the phase 3 studies U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026), and UST 6 mg/kg IV at week 0 with 8-week follow up or PBO in the phase 3 study UNIFI (NCT02407236). Efficacy outcomes were stratified by previous biologic exposure (ie, no prior exposure [bio-naïve] or inadequate response, loss of response, or intolerance to biologics [bio-failed]). Baseline characteristics for age, gender, extent and duration of disease, total Inflammatory Bowel Disease Questionnaire score, total Mayo score, high-sensitivity CRP, faecal calprotectin levels, weight, and UC medication use from the UPA trials were weighted to match the UNIFI trial. Efficacy outcomes at Week 8 were clinical remission per full Mayo score (FMS; FMS ≤2 with no subscore >1), clinical response (decrease in FMS ≥3 points and ≥30%, plus a decrease in rectal bleeding score [RBS] of ≥1 or an absolute RBS of 0 or 1), endoscopic improvement (endoscopic subscore 0 or 1), and histologic-endoscopic mucosal improvement (HEMI). Safety outcomes evaluated in the overall population were adverse events (AEs) and serious AEs (SAEs), comprising the only safety assessments consistently collected across trials. Numbers needed to treat/harm (NNT/NNH) were calculated as the inverse of the difference in proportions achieving efficacy/safety outcomes between UPA and UST. Results The MAIC included 824 UPA and 625 UST pts with efficacy data and 839 UPA and 639 UST pts with safety data. A greater proportion of pts receiving UPA vs UST in bio-naïve and bio-failed groups achieved clinical remission, endoscopic improvement, and HEMI after weighting (p≤0.01, Table 1) with NNTs <10. In bio-naïve pts, differences in the proportion of pts with clinical remission, clinical response, endoscopic improvement, and HEMI for UPA vs UST were 0.172, 0.146, 0.312, and 0.255, respectively, and 0.105, 0.235, 0.135, and 0.118 for bio-failed pts. AEs and SAEs were not statistically different between UPA and UST. Conclusion During induction, greater efficacy with similar safety was observed with UPA vs UST for pts with moderately to severely active UC based on MAIC. Potential bias due to unobserved confounders may exist with MAIC methodology. Further analyses to assess longer-term outcomes are warranted.

Detection of typical indigenous gut bacteria related to turmeric (Curcuma longa) powder in mouse caecum and human faecal cultures.

Turmeric (Curcuma longa; TM) is widely used as a spice and possesses anti-inflammatory, antioxidant, and antibacterial properties. The relationship between TM functions and gut microbiota is still unclear. To investigate the effect of TM on gut microbiota and to identify indigenous gut bacteria that are responsive to TM, we fed Institute of Cancer Research mice a diet containing either no fibre (NF, n = 6) or 5% (w/w) TM (n = 6) for 14days. Moreover, we obtained human stool samples from four healthy volunteers and incubated the samples without (control) or with 2% (w/v) TM at 37°C for 24h. Subsequently, microbiota analysis in murine caecal samples and human faecal cultures was performed using 16S rRNA (V4) amplicon sequencing. Higher faecal weights (p < 0.01) and lower plasma triacylglycerol levels (p < 0.05) were measured in the TM-fed mice than in the NF-fed mice. Furthermore, TM feeding increased the abundance of butyrate-producing and other short-chain fatty acid (SCFA)-producing bacteria in mice as well as in human faecal cultures, and Roseburia bacteria were detected as TM-responsive indigenous gut bacteria (TM-RIB) both in mice and in human faecal cultures. Lastly, in the case of human faecal cultures, SCFA contents and antioxidant properties were higher in TM cultures than in control cultures (p < 0.05). TM appears to hold the potential to positively affect the host by altering the gut microbiota. Further studies are required to clarify the synergistic effects of TM and TM-RIB.

COMPARISON OF ANTI-DIARRHEAL ACTIVITY OF METHANOL AND ETHANOL EXTRACTSS OF WATERMELON RIND(CITRULLUS LANATUS L.) IN WHITE MICE (MUS MUSCULUS)

Watermelon (Citrulluslanatus L.) is one of the most abundant fruit-producing plants in Indonesia. Watermelon is generally only consumed on the red flesh, while the rind is less desirable so that it becomes waste. The purpose of this study was to comparison of anti-diarrheal activity of methanol and 70% ethanol extractss of watermelon rind (citrulluslanatus l.) in white miice (musmuscucolus. This study used a protection method with the induction of MgSO4 (Magnesium Sulfate) by calculating the frequency of diarrhea, changes in stool consistency and stool weight. The data obtained from the activity test results of the watermelon rind methanol extracts against white mice were statistically analyzed using the one-way ANOVA test.Methanolic and 70% ethanolicextractss of watermelon rind (Citruluslanatus L.) contain tannin compounds that have antidiarrheal activity against mice (Musmusculus). From the results of the one-way ANOVA test, the weight of feces, the frequency of diarrhea and the consistency of the stools in the methanol extracts of watermelon rind at a dose of 100 mg/KgBW gave an optimal effect, because the weight of the feces obtained a value of p = 0.633, the frequency of diarrhea obtained a value of p = 0.899 and the consistency of the fecesobtained a value of p = 0.899 p-value = 0.525 compared to the positive control (loperamide). Ethanol extracts of Citrulluslanatus L. had antidiarrheal effect at a dose of 100 mg/kgBW, 200 mg/kgBW, and 300 mg/kgBW. Based on the results of the One Way ANOVA statistical test, the ethanolicextracts of Citrulluslanatus L. had an antidiarrheal effect at a dose of 100 mg/kgBW and the best dose was a dose of 300 mg/kgBW which was significant with the positive control group loperamide P value = 0.000, meaning that the ethanolicextracts of Citrulluslanatus L. at a dose of 300 mg/kgBW had almost the same effect as the loperamide positive control group based on the parameters of stool weight, frequency of diarrhea, and stool consistency. From this data 70% Ethanolic extracts better than methanolicextracts for antidiarrheal activity in mice.

Lactiplantibacillus plantarum X7022 ameliorates loperamide‐induced constipation and modulates gut microbiota in mice

AbstractLactiplantibacillus plantarum X7022 is a novel strain isolated from stinky tofu brine. Its constipation amelioration potential was evaluated on two different constipation types (acute and subacute) in mice induced by loperamide hydrochloride in present work. L. plantarum X7022 could significantly decrease the first black stool defecation time, and increase black fecal weight, number, and the gastrointestinal transit ratio in both models. High‐dose treatment of L. plantarum X7022 (2 × 1010 CFU/kg BW) was more significant in improving constipation condition than low‐dose (2 × 107 CFU/kg BW). Furthermore, 16S rDNA sequencing of the intestinal flora showed that the treatment with the strain X7022 could increase the α diversity in both constipation models. Meanwhile, the abundance of Bacteroidetes increased, and Firmicutes decreased, which was more effective in acute constipated mice. In addition, X7022 treatment could enhance the relative abundance of beneficial flora, such as Bacteroides, Ruminococcus, and depressed Adlercreutzia and Odoribacter in acute model mice. In subacute constipated mice, X7022 treatment could enhance Alloprevotell, Rikenellaceae_RC9, and decreased Lachnospiraceae_NK4A136 and Desulfovibrio. Therefore, L. plantarum X7022 is a prospect probiotic strain for the amelioration of constipation.

Anti-Diarrheal Activities of Hydromethanolic Crude Extract and Solvent Fractions of Acacia seyal (Fabaceae) Roots in Mice.

Traditionally, the root of Acacia seyal is used for the treatment of diarrhea. However, its efficacy has not been scientifically evaluated. Thus, this study aimed to validate the antidiarrheal activities using hydromethanolic crude extract and solvent fractions of Acacia seyal roots in mice. In each model, mice were divided into five groups of six mice at random. Group I mice (negative controls) were given 1mL/100 g distilled water for hydromethanolic crude extract tests as well as n-hexane, ethyl acetate and aqueous fractions, while groups II, III, and IV were given 100 mg/kg, 200 mg/kg, and 400 mg/kg of hydromethanolic crude extract or solvent fractions. Group V mice (positive control) were given 3 mg/kg Loperamide for the castor oil-induced diarrhea and enteropooling test. All of the doses were taken orally. However, Atropine sulfate, 5 mg/kg, was given intraperitoneally for the gastrointestinal motility test. Statistical Package for the Social Sciences (SPSS) version 26 was used to examine the statistical significance of differences in the number and weight of wet and total feces, distance traveled by a charcoal meal, and intestinal fluid accumulation across groups. When compared to the vehicle-treated group, the crude extract and n-hexane fraction notably delayed the onset of diarrhea, reduced the weight and volume of intestinal contents, and hindered the intestinal transit at all tested doses (P < 0.001). The ethyl acetate fraction also significantly (P < 0.001) decreased the weight of intestinal content at all doses examined. Only at 400 mg/kg did the aqueous fraction statistically (P < 0.01) prolonged the onset of diarrhea and impeded gastrointestinal motility. According to this study, the hydromethanolic crude extract and solvent fractions of Acacia seyal roots have promising antidiarrheal effects.

S566 Evaluation of Secondary Bile Acids in Stool as Predictors of Chronic Bile Acid (BA) Diarrhea

Introduction: Bile acid diarrhea (BAD) accounts for ∼25% of chronic “functional diarrhea” (FD). Diagnosis of BAD is currently based on serum 7αC4 >52ng/mL, total fecal BA (TBA) >2,337 µmol/48h, or fecal primary BAs [cholic acid (CA) and chenodeoxycholic acid (CDCA)] >10%. Secondary BAs [deoxycholic acid (DCA) and lithocholic acid (LCA)] are produced by 7α dehydroxylation of CA and CDCA, respectively. DCA promotes colonic secretion, serotonin release, and peristalsis. LCA is a potent stimulus of the Takeda G-protein coupled BA receptor (TGR5, or GPBAR1) which is a mechanism accelerating colonic transit. However, the utility of fecal secondary BAs (DCA and LCA) as markers of both diarrhea [increased fecal weight (FW)] and BAD is unclear. Methods: We conducted a retrospective study of fecal BA 48h data of 913 patients with FD and no prior intestinal surgery or active inflammatory disease. Patients consumed a 100g fat diet for four days with stool collection in the final 48h. Objective diarrhea was defined as FW >400 g/48h. Associations between TBA, main BA components, observed FW, or objective diarrhea (FW >400g/48h) were assessed using linear or logistic regression as appropriate. Multivariate analyses, adjusting for age, sex, and other fecal BAs, were conducted to appraise the role of each BA component. Results: Mean age was 51.5y (range: 11-90y), and 67.6% were female. Mean 48h FW was 546.1g (10-90%ile: 158-1056g). Mean TBA was 1921 µmol/48h (10-90%ile: 256-4328 µmol/48h). In the adjusted analyses, a 2-fold increase in CA and LCA was associated with 12.2% (95% CI: 7.4%-17.2%, p < 0.05) and 15.3% (7.9%-23.1%, p < 0.05) increases in FW, respectively. In contrast, a 2-fold increase in DCA was associated with a 6.8% (1.4%-11.9%, p < 0.05) decrease in FW. Table presents risk of FW >400g [OR (95% CI)] for a 2-fold increase in each BA (adjusted for age and sex) in all patients, and in 2 groups without or with BAD based on TBA >2,337 µmol/48h. The 48h total LCA conferred the greatest risk. In all patients, 48h fecal LCA of 360 µmol/48h had 46% sensitivity and 80% specificity for FW >400g (AUC=0.62, Figure). Adding total LCA to the prediction from total primary BAs increased the AUC from 0.75 to 0.78. Conclusion: Among patients presenting with FD, 48h fecal total LCA is associated with FW >400g with comparable risk estimates to total primary BAs and with CA alone. Therefore, fecal LCA also has potential utility in the diagnosis of BAD.Figure 1.: Receiver operating characteristic (ROC) curve for LCA as a predictor of objective diarrhea Table 1. - Estimated risk of diarrhea (fecal weight >400 g/48 hours) for 2-fold increase in bile acid component Bile Acid All patients(N=913) TBA < 2,337 µmol/48h(N=676) TBA > 2,337 µmol/48h(N=237) CA 1.34 (1.16-1.55)*** 1.22 (1.03-1.46)* 1.66 (1.11-2.49)* CDCA^ 0.98 (0.84-1.14) 0.95 (0.79-1.15) 0.73 (0.49-1.10) DCA^ 0.80 (0.67-0.95)* 0.82 (0.67-1.01) 0.51 (0.34-0.76)** LCA 1.47 (1.20-1.80)*** 1.34 (1.06-1.69)* 2.12 (1.41-3.19)*** UDCA 1.07 (0.99-1.15) 1.11 (1.02-1.22)* 0.91 (0.75-1.11) TBA=total fecal bile acid; UDCA=ursodeoxycholic acid.^secretory BA.*p<0.05.**p<0.01.***p<0.0005.

Ingestion of Indigestible Cacao Proteins Promotes Defecation and Alters the Intestinal Microbiota in Mice

ABSTRACTBackgroundIn animals, the health effects of ingested cacao proteins are unknown because the proteins are difficult to extract and purify from cacao beans.ObjectivesThis study aimed to develop an extraction and purification method for cacao proteins and reveal the effect of ingestion of cacao proteins on defecation and intestinal microbiota in mice.MethodsThree groups of mice were fed a control diet (AIN-93 G), a cacao lignin diet (AIN-93 G containing 1.22% cacao lignin), or a cacao protein and lignin diet (AIN-93 G containing 1.97% cacao proteins and 1.22% cacao lignin) by pair-feeding for 8 d. Feces were collected as 2 bulked samples from days 1 to 4 and days 5 to 8 on each diet. The collected feces were weighed and the intestinal microbiota was analyzed by next-generation sequencing-based 16S rRNA.ResultsA new extraction and purification method for cacao proteins has been developed, then found that the proteins are resistant to digestive enzymes. However, the cacao protein powder made by this method contained 34.9% of lignin in addition to 56.4% of proteins. Therefore, to reveal the effect by cacao proteins alone, the fecal weight and intestinal microbiota of mice fed the cacao protein and lignin diet were compared with those of mice fed the cacao lignin diet. The fecal weight of mice fed the cacao protein and lignin diet was significantly greater than of mice fed the cacao lignin diet. The relative abundance of Lactococcus and Mucispirillum species in mice fed the cacao protein and lignin diet was significantly higher than in mice fed the cacao lignin diet, but the relative abundance of Anaerotruncus, Oscillospira, and Roseburia species in mice fed the cacao protein and lignin diet was significantly lower than in mice fed the cacao lignin diet.ConclusionsIngestion of indigestible cacao proteins promoted defecation and altered the intestinal microbiota such as Lactococcus, Mucispirillum, Anaerotruncus, Oscillospira, and Roseburia species in mice.

LimosiLactobacillus pentosus Isolated from Mustard Relieves Drug-induced Constipation in Mice Fed a High-fat Diet by Modulating Enteric Neurotransmitter Function.

Functional constipation is one of the most common gastrointestinal disorders. Oxidative stress can aggravate organ dysfunction. Enteric neurotransmitters have significant effects on the regulation of the enteric nervous system and intestinal muscle contraction. Oxidative stress and reduced gastrointestinal motility are considered to be one of the main causes of constipation. This study aimed to investigate whether LimosiLactobacillus pentosus CQZC02 alleviated loperamide hydrochloride (Lop)-induced constipation in mice under high-fat diet (HFD) conditions and to elucidate the underlying mechanism, focusing on enteric neurotransmitters. Four-week-old female BALB/c mice were randomly divided into five groups: normal group (Nor), constipation model group (H-Lop), L. pentosus CQZC02 low-dose group (H-Lop + ZC02L), L. pentosus CQZC02 high-dose group (H-Lop + ZC02H), and LimosiLactobacillus bulgaricus control group (H-Lop + LB). The fecal weight, water content, and total gastrointestinal transit time were measured to determine whether the mice were constipated. Small bowel and colon tissue damage was assessed by hematoxylin and eosin staining, while the degree of damage was determined by double-blind scoring. The levels of serum oxidative stress markers malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase and neurotransmitters motilin, gastrin, substance P, endothelin, somatostatin, and vasoactive intestinal peptide were measured. The gene expression levels of endothelial nitric oxide synthase, inducible nitric oxide synthase, neuronal nitric oxide synthase, nuclear factor kappa-B, and cyclooxygenase-2 in small intestine tissue were calculated. The constipation symptoms of mice in H-Lop group were manifested by a variety of physiological indicators. In addition, compared with the H-Lop group, H-Lop + ZC02H could effectively relieve the symptoms of constipation in mice. In symptom characterization, the mice in the H-Lop + ZC02H group lost weight and increased feces and water content. In functional experiments, gastrointestinal motility was enhanced; the inflammation score of intestinal tissue was decreased, and gene expression levels were modulated; serum oxidative factor levels were modulated, and oxidative stress levels were decreased.

Neonatal antibiotics have long term sex-dependent effects on the enteric nervous system.

Infants and young children receive the highest exposures to antibiotics globally. Although there is building evidence that early life exposure to antibiotics increases susceptibility to various diseases including gut disorders later in life, the lasting impact of early life antibiotics on the physiology of the gut and its enteric nervous system (ENS) remains unclear. We treated neonatal mice with the antibiotic vancomycin during their first 10 postnatal days, then examined potential lasting effects of the antibiotic treatment on their colons during young adulthood (6weeks old). We found that neonatal vancomycin treatment disrupted the gut functions of young adult female and male mice differently. Antibiotic-exposed females had significantly longer whole gut transit while antibiotic-treated males had significantly lower faecal weights compared to controls. Both male and female antibiotic-treated mice had greater percentages of faecal water content. Neonatal vancomycin treatment also had sexually dimorphic impacts on the neurochemistry and Ca2+ activity of young adult myenteric and submucosal neurons. Myenteric neurons of male mice were more disrupted than those of females, while opposing changes in submucosal neurons were seen in each sex. Neonatal vancomycin also induced sustained changes in colonic microbiota and lasting depletion of mucosal serotonin (5-HT) levels. Antibiotic impacts on microbiota and mucosal 5-HT were not sex-dependent, but we propose that the responses of the host to these changes are sex-specific. This first demonstration of long-term impacts of neonatal antibiotics on the ENS, gut microbiota and mucosal 5-HT has important implications for gut function and other physiological systems of the host. KEY POINTS: Early life exposure to antibiotics can increase susceptibility to diseases including functional gastrointestinal (GI) disorders later in life. Yet, the lasting impact of this common therapy on the gut and its enteric nervous system (ENS) remains unclear. We investigated the long-term impact of neonatal antibiotic treatment by treating mice with the antibiotic vancomycin during their neonatal period, then examining their colons during young adulthood. Adolescent female mice given neonatal vancomycin treatment had significantly longer whole gut transit times, while adolescent male and female mice treated with neonatal antibiotics had significantly wetter stools. Effects of neonatal vancomycin treatment on the neurochemistry and Ca2+ activity of myenteric and submucosal neurons were sexually dimorphic. Neonatal vancomycin also had lasting effects on the colonic microbiome and mucosal serotonin biosynthesis that were not sex-dependent. Different male and female responses to antibiotic-induced disruptions of the ENS, microbiota and mucosal serotonin biosynthesis can lead to sex-specific impacts on gut function.

Effect of Bacillus coagulans SNZ 1969 on the Improvement of Bowel Movement in Loperamide-Treated SD Rats.

Bacillus coagulans SNZ 1969 (B. coagulans SNZ 1969) is a spore-forming bacterium reported to be effective in attenuating constipation. However, there is no study on whether B. coagulans SNZ 1969 could improve constipation through mucin secretion and changes in intestinal hormones. To address this knowledge gap, rats were orally administrated with various treatments for four weeks. The normal control (NOR) group received saline only. There were four constipation-induced groups. The LOP group received only loperamide (LOP), a constipation-inducing agent. The BIS group received both LOP and Bisacodyl (BIS, a constipation treatment agent). The SNZ-L group received both LOP and B. coagulans SNZ 1969 at 1 × 108 CFU/day. The SNZ-H group received LOP and B. coagulans SNZ 1969 at 1 × 1010 CFU/day. As indicators of constipation improvement, fecal pellet weight, fecal water content, gastrointestinal transit time, and intestinal motility were measured. Mucus secretion in the colon was determined by histological colon analysis and mucin-related gene expressions. Gastrointestinal (GI) hormones were also measured. SNZ-L and SNZ-H groups showed significantly increased fecal weights, fecal water contents, and intestinal motility than the LOP group. SNZ-L and SNZ-H groups also showed higher secretion of mucin in the colon and mRNA expression levels of Mucin 2 and Aquaporin 8 than the LOP group. The SNZ-H group showed significantly increased substance P but significantly decreased somatostatin and vasoactive intestinal peptide than the LOP group. The results of this study suggest that B. coagulans SNZ 1969 intake could attenuate constipation through mucin secretion and alteration of GI hormones.

Effect of miR-129-3p on autophagy of interstitial cells of Cajal in slow transit constipation through SCF C-kit signaling pathway.

To explore the mechanism by which miR-129-3p affected the autophagy of interstitial cells of Cajal (ICCs) in slow transit constipation tissues through the SCF C-kit signaling pathway. Colon samples from 20 Slow transit constipation (STC) patients who underwent total colectomy plus ileorectal anastomosis or subtotal colon resection plus anti-peristaltic rectal anastomosis were collected in our hospital. The colon of 20 non-STC patients was used as control. The control of this study was 20 patients undergoing radical surgery for colon cancer (left colon cancer) in our hospital. Fifty healthy SPF Kunming mice were purchased from Liaoning Changsheng Biotechnology Co., Ltd. The mRNA expression of miR-129-3p in the STC group was lower than that in the control group (CTLR) group (P<0.05). The mRNA expression of miR-129-3p in STC group was lower than that in the NC group (P<0.05), and mRNA expression in STC+miR-129-3p group was higher than that in STC+miR-NC group (P<0.05). In the first week, the weight of dry and wet feces of the STC group was lower than that of the NC mice (P<0.05), and the weight of dry feces and wet feces of the STC group was lower than that of the NC group at the 2, 3, and 4 weeks, STC+miR-129 -3p was higher than that in the STC group (P<0.05). The increased expression of C-kit and SCF regulated by miR-129-3p contributed to the protection of interstitial cells. Knockdown of miR-129-3p expression could inhibit the activation of AKT/mTOR signaling pathway, reduce cell proliferation activity.

In Vivo Efficacy, Toxicity Assessment, and Elemental Analysis of Traditionally Used Polyherbal Recipe for Diarrhea.

A polyherbal formulation consisting of Mentha piperita L., Camellia sinensis L. Kuntze, and Elettaria cardamomum (L.) Maton with a ratio of 10 : 5 : 2, respectively, was recommended for curing nausea, vomiting, and diarrhea. Experimental validation is crucial to affirm its therapeutic property leads toward the development of modified antidiarrheal agents. This research aimed to investigate the in vivo antidiarrheal efficacy of traditionally used polyherbal recipe in a castor oil-induced animal model. Moreover, the study also presents the elemental screening and in vivo toxicity of tested polyherbal recipe. Individual plant parts of the polyherbal recipe were mixed according to the traditional prescription ratio, and hydromethanolic extract was prepared by the cold maceration process. The antidiarrheal activity was assessed by castor oil induction method, charcoal meal test, and enteropooling procedure in Sprague-Dawley rats. Elemental analysis and in vivo subacute toxicity were carried out, followed by biochemical, hematological, and histopathological analyses. Polyherbal extract significantly delayed the diarrhea onset in a dose-dependent manner and showed marked inhibition at 200 and 400 mg/kg. Fecal weight was reduced significantly (p < 0.05) at 200 mg/kg (0.26 ± 0.25) in comparison with the control (1.63 ± 0.15). The diarrhea score was zero at a concentration of 200 and 400 mg/kg. Antienteropooling effect of the extract was greater than that of loperamide. Following subacute toxicity, all the treated rats were normal, survived, and showed no changes in behavior. There were no significant differences between values of blood parameters in both the control and extract-treated groups except a significant decrease in monocytes (control 8.4; polyherbal 2.2). Elemental analysis showed a slight increase in the amount of manganese (Mn, 8.076 ppm) as compared to the WHO recommended level (2 ppm). Traditionally used polyherbal recipe is effective and safe for combating diarrheal diseases. In vivo evidence supported the use, safety, and efficacy of the polyherbal recipe that has been used as an alternative medicine for diarrhea in the study area. Inhibition of castor oil-induced diarrhea and antisecretory effect of the studied polyherbal recipe makes it a potent antidiarrheal drug without no or limited toxic effects at the tested dose after further analysis.

Feeding Our Microbiota: Stimulation of the Immune/Semiochemical System and the Potential Amelioration of Non-Communicable Diseases.

Non-communicable diseases are those conditions to which causative infectious agents cannot readily be assigned. It is increasingly likely that at least some of these conditions are due to the breakdown of the previously mutualistic intestinal microbiota under the influence of a polluted, biocide-rich, environment. Following the mid-20th century African studies of Denis Burkitt, the environmental cause of conditions such as obesity has been ascribed to the absence of sufficient fibre in the modern diet, however in itself that is insufficient to explain the parallel rise of problems with both the immune system and of mental health. Conversely, Burkitt himself noted that the Maasai, a cattle herding people, remained healthy even with their relatively low intake of dietary fibre. Interestingly, however, Burkitt also emphasised that levels of non-communicable disease within a population rose as faecal weight decreased significantly, to about one third of the levels found in healthy populations. Accordingly, a more cogent explanation for all the available facts is that the fully functioning, adequately diverse microbiome, communicating through what has been termed the microbiota–gut–brain axis, helps to control the passage of food through the digestive tract to provide itself with the nutrition it needs. The method of communication is via the production of semiochemicals, interkingdom signalling molecules, potentially including dopamine. In turn, the microbiome aids the immune system of both adult and, most importantly, the neonate. In this article we consider the role of probiotics and prebiotics, including fermented foods and dietary fibre, in the stimulation of the immune system and of semiochemical production in the gut lumen. Finally, we reprise our suggestion of an ingestible sensor, calibrated to the detection of such semiochemicals, to assess both the effectiveness of individual microbiomes and methods of amelioration of the associated non-communicable diseases.

Anti-diarrhoeal effects of Garcinia kola (Heckel-Holl) seed methanolic extract and its fractions in animal models

This study investigated the In vitro spasmolytic and In vivo anti-diarrhoeal effects of Garcinia kola seed extract/fractions. Extraction was done by maceration in 70% methanol, serially partitioned in ethyl acetate and n-hexane. Qualitative phytochemical screening was carried out on the crude extract/fractions. The In vitro spasmolytic effect of the extract and fractions at different concentrations (0.5×103, 0.2×103,0.1×103, 0.6×102 mg/ml) were investigated against spontaneous and acetylcholine-induced contractions in isolated rabbit jejunum as well as histamine-induced contractions using isolated guinea pig ileum. The In vivo anti-diarrhoeal effect of the extract was evaluated using three diarrhoeal models: castor oil-induced diarrhoea, charcoal meal gastrointestinal transit time and castor oil-induced enteropooling. In each model, 25 mice were randomly divided into five groups of 5 mice each. Group I served as the untreated control, while group II was a positive control. Groups III-V were administered 125, 250 and 500 mg/kg of the crude methanol extract, respectively. The crude extract, ethyl acetate and aqueous fractions at 0.5×103 mg/ml respectively exhibited 14.4%, 12.9% and 12.2% spasmolytic activities against acetylcholine-induced rabbit jejunum contractions. Histamine-induced guinea pig ileum contractions were inhibited by crude extract (6.2%), ethyl acetate (6.2%), aqueous fraction (7.2%) at 0.6×102 mg/ml. For castor oil-induced diarrhoea, the crude extract at 500 mg/kg produced a significant (p &lt; 0.05) decrease in the diarrhoeal index and faecal weight with a percentage inhibition of 70.4% compared with controls. Similarly, the crude extract (500 mg/kg) significantly (p &lt; 0.05) decreased the charcoal meal gastrointestinal transit time with a percentage inhibition of 33.9% and elicited significant (p &lt; 0.05) intraluminal fluid reduction (9.1%) in castor oil-induced enter pooling test when compared with the untreated group. In conclusion, the anti-motility and anti-secretory activities of the crude extract were attributed to the phytochemical constituents present.

Associations between intestinal microbiota, fecal properties, and dietary fiber conditions: The Japanese traditional medicine Junchoto ameliorates dietary fiber deficit-induced constipation with F/B ratio alteration in rats.

Changes in the intestinal microbiota are known to occur in constipated patients. Dietary fiber restriction presents obstacles to appropriate defecation and affects fecal properties, but the relationship between fecal microbiota and fecal morphological properties remains obscure. Therefore, we examined the influence of fiber diets on the fecal microbiome and properties in rats, and the effectiveness of the Japanese traditional medicine Junchoto (JCT) in rats with fiber deficit-induced constipation. Rats were fed three different fiber diets with varying cellulose contents (0%, FFD; 5%, ND; 15%, HFD), respectively, as follows: study 1: 21 days of feeding; study 2: 14 days of feeding followed by 7 days of ND (fiber normalization in all groups); study 3: FFD for 21 days, followed by JCT administration from 14 days. Fecal properties and 16S rRNA amplicon sequencing results were examined. We observed that the fecal frequency, dry weight, and length were increased, and water ratio were decreased in a cellulose dose-dependent manner. The difference in several kinds of fecal microbiota, but not the α-diversity Chao1 index and the Firmicutes/Bacteroidetes ratio (F/B ratio), between groups were observed. The change in fecal property in both the HFD and FFD groups was ameliorated with fiber normalization, accompanied by alteration of the Chao1 index and/or F/B ratio. JCT administration reversed the fecal morphological changes in FFD group, accompanied by F/B ratio increasing. In conclusion, short-term dietary changes modulated microbial homeostasis, which is linked to fecal property. JCT may alter the F/B ratio and improve fecal properties to facilitate easier excretion.

Evaluation of Antidiarrheal Activity of Leea aequata L. (Family: Vitaceae) in Mice Models

Diarrhea is one of the most common reasons for why thousands of people die every year particularly in the underdeveloped and developing country. Furthermore, the identification of new antidiarrheal medication sources has become one of the most prominent areas of contemporary study. In addition, the plants of the Leea species are used traditionally for the treatment of diarrhea in different cultures. Considering this background, present study was to look into the antidiarrheal effects of an ethanolic extract of Leea aequata L. leaves in mice. The castor oil induced diarrhea and the small intestinal transit models were utilized in this study to examine the extract's potential antidiarrheal efficacy. The extract was given to the test groups in various quantities (100, 200 mg/kg), whereas positive controls got loperamide (3 mg/kg) and negative controls received distilled water (10 ml/kg). In a model of diarrhea caused by castor oil, 200 mg/kg of the extract significantly (p&lt;0.01) decreased the total number of bowel movements. The extracts also demonstrate a substantial (p&lt;0.05) reduction in the frequency of wet defecation at all doses. The onset of diarrhea was extended with dose of the extracts which is statistically significant (p&lt;0.001). At higher doses, the extract caused a significant (p&lt;0.05) reduction in the weight and volume of wet feces. Furthermore, in the charcoal meal test, increasing doses of the extract caused a substantial (p&lt;0.01) reduction in gastrointestinal motility. Phytochemical screening of the extract revealed the presence of flavonoids, alkaloids, tannins, and phytosterols that may play a key role in its antidiarrheal activity. The results of our study indicate that bioactive compounds are present in ethanolic leaf extract of our plant including significant antidiarrheal activity and thus provide the scientific basis for the traditional uses of this plant as a treatment for diarrhea. Bangladesh Pharmaceutical Journal 25(2): 180-187, 2022 (July)

The potential of ethanol extracts 96% mature Papaya fruit seeds (Carica papaya L) as anti-diarrhea medicine

Mature papaya fruit seeds (Carica papaya L.) reduce diarrhea because of phytochemical compounds. This study aimed to determine the potential of 96% ethanol extract of mature papaya fruit seeds as antidiarrhea. This study used experimental laboratory research with pre and post-test with control group design. The research subjects were 25 mice divided into 5 groups, KI group (negative control), KII (positive control) loperamide, and KIII-KIV-KV given treatment with a dose (200 mg; 400 mg; 800 mg). A decrease in diarrhea is known by observing the consistency of feces, stool weight, and stool diameter. Data were analyzed by the Kruskal Wallis test and the Mann Whitney Post Hoc test. The results of the consistency of feces in group K(I) were compared with groups of K(II), K(III), K(IV), K(V) p=0.046, 0.083, 0.014, and 0.014. In stool weight K(I) compared to K(II), K(III), K(IV), K(V) with p=0.053, 0.102, 0.016, and 0.053. In the observation of absorption diameter K(-) compared to K(+), KI(200), KII(400), KIII(800) the p=0.121, 0.0197, 0.051 and 0.21. In conclusion, the mature extract papaya fruit seeds can reduce diarrhea seen from the stool consistency in the group extract 400 and 800 mg/Kilograms body weight and fecal weight in the 400mg/Kilograms body weight extract group.

Evaluation of In vivo antidiarrheal activity of hydro-methanolic extract of the root of Rumex nepalensis in Swiss Albino mice

BackgroundNatural products have been utilized by human beings for thousands of years to relieve a variety of ailments, including diarrhea. Conventional antidiarrheal drugs are associated with multiple adverse effects and contraindications. Traditionally, Rumex nepalensis by crushing the root, mix with water and then drunk the juice is extensively used for treating diarrhea. However, no scientific research has been done yet to support its antidiarrheal efficacy and safety. Hence, the aim of the study was to evaluate the antidiarrheal activity and safety profile of the plant in mice. MethodsThe hydro-methanolic extract was extracted through a cold maceration technique using 80% methanol. Castor oil-induced diarrheal, gastro-intestinal transit, and enteropooling models have been employed to assess the antidiarrheal activity of the test extract at doses of 100, 200, and 400 mg/kg. ResultsThe crude root extract caused no mortality at a single limit test dose of 2 g/kg throughout the first 24 h and for the rest of the 14 days. In a castor oil-induced diarrheal model, the hydro-methanolic extract markedly delayed the onset of diarrhea, reduced the weight of wet and total feces at 100 (P<.05), 200 (P<.01), and 400 mg/kg (P<.001) test doses. Meanwhile, at 200 (P<.01) and 400 mg/kg (P<.001) doses, the plant extract considerably lowered the weight and volume of intestinal contents. In the gastro-intestinal transit model, however, a dramatic inhibition in the charcoal meal travel was noticed at 100 (P<.05), 200 (P<.01), and 400 mg/kg (P<.001) test doses. The peak antidiarrheal index was exhibited at the highest dose of the test extract. ConclusionThe study speculated that Rumex nepalensis root extract possesses antidiarrheal activity, which could be owing to its inhibitory effect on both gastro-intestinal motility and fluid secretion.

Synthesized effects of medium-term exposure to seawater acidification and microplastics on the physiology and energy budget of the thick shell mussel Mytilus coruscus

Ocean acidification (OA) and microplastics (MPs) contamination are two results of human excises. In regions like estuarine areas, OA and MPs exposure are happening at the same time. The current research investigated the synthesized effects of OA and MPs exposure for a medium-term duration on the physiology and energy budget of the thick shell mussel Mytilus coruscus. Mussels were treated by six combinations of three MPs levels (0, 10 and 1000 items L−1) × two pH levels (7.3, 8.1) for 21 d. As a result, under pH 7.3, clearance rate (CR), food absorption efficiency (AE), respiration rate (RR), and scope for growth (SFG) significantly decreased, while the fecal organic dry weight ratio (E) significantly increased. 1000 items L−1 MPs led to decrease of CR, E, SFG and increase of AE under pH 8.1. Interactive effects from combination of pH and MPs were found in terms of CR, AE, E and RR, but not for SFG of M. coruscus.