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Cell and Tissue Research May 2024Motilin (MLN) is a peptide hormone originally isolated from the mucosa of the porcine intestine. Its orthologs have been identified in various vertebrates. Although MLN...
Motilin (MLN) is a peptide hormone originally isolated from the mucosa of the porcine intestine. Its orthologs have been identified in various vertebrates. Although MLN regulates gastrointestinal motility in tetrapods from amphibians to mammals, recent studies indicate that MLN is not involved in the regulation of isolated intestinal motility in zebrafish, at least in vitro. To determine the unknown function of MLN in teleosts, we examined the expression of MLN and the MLN receptor (MLNR) at the cellular level in Japanese medaka (Oryzias latipes). Quantitative PCR revealed that mln mRNA was limitedly expressed in the gut, whereas mlnr mRNA was not detected in the gut but was expressed in the brain and kidney. By in situ hybridization and immunohistochemistry, mlnr mRNA was detected in the dopaminergic neurons of the area postrema in the brain and the noradrenaline-producing cells in the interrenal gland of the kidney. Furthermore, we observed efferent projections of mlnr-expressing dopaminergic neurons in the lobus vagi (XL) and nucleus motorius nervi vagi (NXm) of the medulla oblongata by establishing a transgenic medaka expressing the enhanced green fluorescence protein driven by the mlnr promoter. The expression of dopamine receptor mRNAs in the XL and cholinergic neurons in NXm was confirmed by in situ hybridization. These results indicate novel sites of MLN activity other than the gastrointestinal tract. MLN may exert central and peripheral actions through the regulation of catecholamine release in medaka.
PubMed: 38727755
DOI: 10.1007/s00441-024-03896-5 -
Nutrients Sep 2023Constipation is currently one of the most common gastrointestinal disorders, and its causes are diverse. Multi-strain probiotics are often considered a more effective...
Constipation is currently one of the most common gastrointestinal disorders, and its causes are diverse. Multi-strain probiotics are often considered a more effective treatment than single-strain probiotics. In this study, a constipation model was constructed using loperamide hydrochloride to evaluate the ability of a multi-strain probiotic combination of four different ratios of and to regulate intestinal flora, relieve constipation, and explore the initial mechanism in mice. After four weeks of probiotic intervention, BM1, BM2, and PB2 effectively relieved constipation; however, the pathways involved were different. The -dominated formulations BM1 and BM2 mainly changed the composition and structure of the intestinal flora and significantly decreased the relative abundance of , , , , and in stool; increased the relative abundance of and the content of short-chain fatty acids (SCFAs) in stool; restored motilin (MTL) and vasoactive intestinal peptide (VIP) levels; and downregulated interleukin 6 (IL-6) and IL-8 levels in serum. This repaired the inflammatory response caused by constipation. Finally, it promoted peristalsis of the gastrointestinal tract, increasing stool water content, and relieving constipation. While -dominated formula PB2 mainly restored the levels of serum neurotransmitters (MTL, SP (substance P), VIP and PYY (Peptide YY)) and inflammatory factors (IL-1, IL-6 and IL-8), it significantly decreased the relative abundance of , , , and in stool; it then increased acetic acid content, thereby reducing the level of inflammation and changing stool properties and gastrointestinal motility.
Topics: Animals; Mice; Loperamide; Lactobacillus; Bifidobacterium; Interleukin-6; Interleukin-8; Constipation; Gastrointestinal Diseases; Probiotics
PubMed: 37836514
DOI: 10.3390/nu15194230 -
Combinatorial Chemistry & High... 2023The aim of the study was to explore the efficacy as well as the mechanism of action of Pitongshu (PTS) on rats with functional dyspepsia (FD) induced by iodoacetamide...
AIM
The aim of the study was to explore the efficacy as well as the mechanism of action of Pitongshu (PTS) on rats with functional dyspepsia (FD) induced by iodoacetamide gavage and tail clamping.
METHODS
The bioactive components of PTS were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), whereas the potential targets of PTS were obtained from the Similarity Ensemble Approach (SEA), TCMSP, and Swiss Target Prediction Database. The disease targets were obtained from the DisGeNET database, whereas Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the R Software. The method of iodoacetamide gavage combined with tail clamping was used to establish the FD rat model in this study. Body weight, food intake, gastrointestinal motility, gastric acidity and secretion, and the mechanical pain threshold of rats were measured. The open-field test was also performed. The stomach and duodenum were histologically observed. The levels of serotonin (5-HT), Calcitonin Gene-Related Peptide (CGRP), Motilin (MTL), and Gastrin (GAS) in gastric tissues were detected by ELISA.
RESULTS
A total of 139 bioactive components and 17 potential targets of PTS were identified through a network pharmacology approach. The results of GO and KEGG enrichment analyses indicated that PTS could reduce the 5-HT secretion of gastric tissues through the serotonergic synaptic pathway and alleviate the symptoms of FD, indicating that PTS plays a therapeutic role. The results of animal experiments showed that PTS could increase body weight and food intake, improve autonomous activity, and decrease gastric acidity and secretion in FD rats. Furthermore, gastric sensitivity increased in FD rats, and PTS treatment could significantly decrease it. The results of ELISA showed that the overexpression of 5-HT and CGRP was decreased after PTS treatment in FD rats. Lastly, PTS could significantly improve gastrointestinal motility, as well as the levels of GAS and MTL in FD rats.
CONCLUSION
PTS may reduce 5-HT secretion by regulating the serotonergic synaptic pathway, thereby reducing visceral sensitivity and alleviating the symptoms of FD.
Topics: Rats; Animals; Dyspepsia; Serotonin; Calcitonin Gene-Related Peptide; Iodoacetamide; Gastrointestinal Motility
PubMed: 36043772
DOI: 10.2174/1386207325666220827152654 -
Frontiers in Microbiology 2024Constipation is a common gastrointestinal disease that seriously affects human physical and mental health. Studies have reported that hemp seeds can improve...
Constipation is a common gastrointestinal disease that seriously affects human physical and mental health. Studies have reported that hemp seeds can improve constipation, however the specific mechanism is still unclear. This study investigates that hemp seed (HS) and its water-ethanol extract (HSE) attenuates loperamide-induced constipation in mice. The research results show that: the fecal water content and small intestinal transit rate of mice in the hemp seed group and hemp seed hydroalcoholic extract group were significantly increased compared with MC group, and the first red feces defecation time was significantly shortened; HS and HSE significantly influence serum levels of Gastrin (Gas), motilin (MTL), substance P (SP), and endothelin (ET), potentially mediating their effects on gastrointestinal motility. HS and HSE can improve colon inflammation in constipated mice with H&E staining. Compared with the model of constipation group, the content of short-chain fatty acids in the HS group and HSE group increased significantly. Gut microbiome studies have shown that the structure and abundance of intestinal flora are altered. HS and HSE changed the abundance of . Together, these results suggest that HS have the potential to stimulate the proliferation of beneficial gut microbes and promote intestinal motility, thereby improving gut health and relieving symptoms of constipation.
PubMed: 38638898
DOI: 10.3389/fmicb.2024.1353015 -
Frontiers in Nutrition 2023Our aim was to determine the efficacy of four-week probiotic supplementation on gastrointestinal health. The secondary objectives were to assess probiotic effects on...
OBJECTIVE
Our aim was to determine the efficacy of four-week probiotic supplementation on gastrointestinal health. The secondary objectives were to assess probiotic effects on immune reaction, as well as weight control and metabolic health.
METHODS
We conducted two randomized sub-trials, respectively, among subjects who were diagnosed with functional constipation (FC) or functional diarrhea (FDr) according to the Rome IV criteria. In each sub-trial, 70 eligible Chinese adults were randomized to receive a multi-strain probiotic combination or a placebo. Gastrointestinal symptoms, defecation habits, stool characteristics, blood and fecal biochemistry markers, anthropometrics measures, stress-associated responses, and intestinal flora changes were assessed at baseline and after probiotics intervention.
RESULTS
Four weeks of probiotic supplementation reduced overall gastrointestinal symptoms scores in FC participants ( < 0.0001). Their mean weekly stool frequency increased from 3.3 times to 6.2 times; immune response and inflammation markers improved with increases in serum IgA, IFN-γ and fecal sIgA, and decrease in hsCRP; most components of lipid profile were significantly ameliorated, with increases in HDL-C and reductions in TC and TG; body weight, body mass index and basal metabolic rate decreased following probiotics consumption. For FDr participants, probiotics consumption markedly reduced overall gastrointestinal symptom scores ( < 0.0001); decreased stool frequency by 3 times per week; increased IgA, IFN-γ, sIgA concentrations, while lowered hsCRP and IL-4 levels. Both FC and FDr participants had improvement in the scores of defecation habits, anxiety or depression, and perceived stress. Probiotics supplementation promoted the production of all three major short-chain fatty acids. No changes were observed in LDL-C, IgG, IgM, IL-8, IL-10 and motilin.
CONCLUSION
Supplementation with the probiotic formula over a four-week period could help relieving gastrointestinal symptoms, improving satisfaction with defecation habits, emotional state and immune response, and ameliorating dysbacteriosis in participants with FC or FDr. It also had beneficial effects on lipid metabolism and weight control for FC participants.
PubMed: 37497057
DOI: 10.3389/fnut.2023.1196625 -
Food & Function Jun 2020Constipation is a prevalent and burdensome gastrointestinal (GI) disorder that seriously affects the quality of human life. This study evaluated the effects of the P....
Constipation is a prevalent and burdensome gastrointestinal (GI) disorder that seriously affects the quality of human life. This study evaluated the effects of the P. pentosaceus B49 (from human colostrum) on loperamide (Lop)-induced constipation in mice. Mice were given P. pentosaceus B49 (5 × 109 CFU or 5 × 1010 CFU) by gavage daily for 14 days. The result shows that P. pentosaceus B49 treatment relieved constipation in mice by shortening the defecation time, increasing the GI transit rate and stool production. Compared with the constipation control group, the P. pentosaceus B49-treated groups showed decreased serum levels of inhibitory neurotransmitters (vasoactive intestinal peptide and nitric oxide), increased serum levels of excitatory neurotransmitters (acetylcholinesterase, motilin, and gastrin), and elevated cecal concentration of short chain fatty acids (SCFAs). Analysis of cecal microbiota reveals that P. pentosaceus B49 was colonized in the intestine of constipated mice, and altered the cecal microbiota by increasing beneficial SCFAs-producing bacteria (i.e., Lactobacillus, Ruminococcaceae_UCG-014, and Bacteroidales_S24-7) and decreasing potential pathogenic bacteria (i.e., Staphylococcus and Helicobacter). Moreover, transcriptome analysis of the colon tissue shows that P. pentosaceus B49 partly normalized the expression of genes related to GI peristalsis (i.e., Ache, Chrm2, Slc18a3, Grp, and Vip), water and electrolyte absorption and transport (i.e., Aqp4, Aqp8, and Atp12a), while down-regulating the expression of pro-inflammatory and pro-oncogenic genes (i.e., Lbp, Lgals2, Bcl2, Bcl2l15, Gsdmc2, and Olfm4) in constipated mice. Our findings indicate that P. pentosaceus B49 effectively relieves constipation in mice and is a promising candidate for treating constipation.
Topics: Acetylcholinesterase; Animals; Bacteria; Colon; Colostrum; Constipation; Fatty Acids, Volatile; Feces; Gastrins; Gastrointestinal Transit; Hormones; Humans; Intestines; Loperamide; Male; Mice; Mice, Inbred BALB C; Milk, Human; Motilin; Neurotransmitter Agents; Oxidative Stress; Pediococcus pentosaceus; Peristalsis; Probiotics; RNA, Ribosomal, 16S; Transcriptome
PubMed: 32525185
DOI: 10.1039/d0fo00208a -
Evidence-based Complementary and... 2020Paeoniflorin, an organic compound extracted from the roots of the white peony () plant, has previously been shown to exert antidepression and prokinetic effects. The...
Paeoniflorin, an organic compound extracted from the roots of the white peony () plant, has previously been shown to exert antidepression and prokinetic effects. The traditional Chinese prescription Si-Ni-San, of which paeoniflorin is a constituent, is often used in treating depression and functional gastrointestinal disorders. The effectiveness of Si-Ni-San has been shown to be less effective in a paeoniflorin-deleted form. The present study further investigates whether paeoniflorin alone is as effective as herbal prescriptions in which the compound is a constituent, specifically any antidepressive and prokinetic effect on rats subjected to a forced swimming test (FST). The FST was used to establish the depression model. Sprague-Dawley rats were administrated with 10 mg/kg paeoniflorin by gastrogavage three times before the behavioral test and gastrointestinal motility tests, respectively. In antidepression studies, fluoxetine was used as the positive control. In order to determine the effect of paeoniflorin on the gastrointestinal movement, mosapride was used as the positive control. Plasma and hippocampus monoamine, hypothalamic-pituitary-adrenal axis, plasma brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), ghrelin, motilin, and hippocampus nitric oxide (NO) were assessed using an enzyme-linked immunosorbent assay (ELISA). Gastrointestinal (GI) motility was measured and . Rats subjected to FST showed decreased gastric emptying and intestinal transit , decreased plasma and hippocampus 5-hydroxytryptamine, norepinephrine, dopamine, ghrelin, motilin, and reduced plasma BDNF and SOD as well as increased plasma and hippocampus corticotropin-releasing hormone, adrenocorticotropic hormone, corticosterone, plasma MDA, and hippocampus NO. Paeoniflorin reversed these symptoms in a similar manner to fluoxetine and mosapride, respectively. , paeoniflorin can stimulate the jejunal contract of healthy rats dose-dependently. The results suggest that paeoniflorin can simultaneously exert antidepression and prokinetic effects via polypharmacology.
PubMed: 32733578
DOI: 10.1155/2020/2153571 -
Frontiers in Surgery 2022To explore the effect of dexmedetomidine (Dex)-assisted intravenous anesthesia on gastrointestinal motility in patients with colon cancer (CC) after open colectomy.
BACKGROUND
To explore the effect of dexmedetomidine (Dex)-assisted intravenous anesthesia on gastrointestinal motility in patients with colon cancer (CC) after open colectomy.
METHODS
A total of 102 patients with CC, undergoing open colectomy in our hospital from January 2018 to January 2020, were selected and randomly divided into an observation group ( = 51) and a control group ( = 51). The patients in the control group received a routine combination of intravenous and inhalation anesthesia (CIIA), while those in the observation group received a Dex-assisted CIIA. The systolic blood pressure (SBP), the diastolic blood pressure (DBP), heart rate (HR), and the mean arterial pressure (MAP) were compared at different time points between the two groups. In addition, the intraoperative general conditions, the dosage of anesthetics, and the recovery of gastrointestinal functions were also compared between the two groups. Moreover, before operation and at 24 h after operation, the levels of serum gastrin (GAS) and plasma motilin (MTL) were detected by radioimmunoassay, and the level of plasma cholecystokinin (CCK) was detected by an enzyme-linked immunosorbent assay. The incidence of gastrointestinal complications was recorded in both groups.
RESULTS
At T-T, the HR, SBP, DBP, and MAP levels were lower in both groups than those at T. In addition, they were also lower in the observation group than those in the control group, showing significant differences ( < 0.05). The dosage of propofol and remifentanil in the observation group was lower than that in the control group, and there was a significant difference ( < 0.05). In the observation group, the postoperative first exhaust time, first defecation time, first ambulation time, and first feeding time were all earlier than those in the control group with significant differences ( < 0.05). After the operation, the observation group had higher levels of GAS and MTL but a lower level of CCK than the control group, and the differences were significant ( < 0.05). The incidence rate of gastrointestinal complications in the observation group (7.04%) was lower than that in the control group (19.61%), and there was a significant difference (χ = 4.346, < 0.05).
CONCLUSIONS
Dex-assisted intravenous anesthesia can facilitate the recovery of gastrointestinal motility, can regulate the levels of gastrointestinal hormones, and can stabilize the levels of hemodynamic indexes in patients with CC after open colectomy.
PubMed: 35284494
DOI: 10.3389/fsurg.2022.842776 -
Frontiers in Nutrition 2022In this article, the preventive and protective effect of a new , ( TKSN02: LF-N2), which was isolated and identified from Xinjiang naturally fermented yogurt, on...
In this article, the preventive and protective effect of a new , ( TKSN02: LF-N2), which was isolated and identified from Xinjiang naturally fermented yogurt, on hydrochloric acid (HCl)/ethanol induced gastric injury in mice was studied. A total of 40 mice were divided into the following five groups: normal, model, LF-N2, LB (), and Ranitidine groups. Except for the normal and model groups, mice in the other groups were treated with LF-N2, LB ( bulgaricus), and Ranitidine separately, and the injury of the gastric tissue was observed by taking photos and pathological sections. The levels of oxidation indicators, gastrointestinal hormone and the inflammatory cytokines in serum and gastric tissue in each group were measured. Further more, the gene expression levels of oxidative stress and inflammation related genes in the colon tissue were determined by the Real-Time PCR method. Pathological observation confirmed that LF-N2 could inhibit the gastric injury caused by HCl/ethanol. Observation of the appearance of the gastric indicated that LF-N2 could effectively reduce the area of gastric injury. Biochemical results showed that the serum gastrin (GAS) and gastric motilin (MTL) levels in the LF-N2 group were significantly lower and the serum somatostatin (SS) level was higher than in the model group and there was no significant difference between all treatment groups. The activities of total superoxide dismutase (T-SOD) and glutathione (GSH) were increased while the malondialdehyde (MDA) content was decreased in LF-N2 treatment group mice, which suggested that LF-N2 has a good antioxidant effect. Further RT-PCR experiments also showed that LF-N2 could promote the related mRNA expression of antioxidant enzymes (Cu/Zn-SOD, Mn-SOD, and CAT) and anti-inflammatory cytokines (IL-4, and IL-10), while it inhibited the gene expression of pro-inflammatory cytokine (IL-6) and apoptosis factor (Caspase-3). As observed, LF-N2 exerted a good preventive effect on HCl/ethanol induced gastric injury in mice, and the effect was close to that of LB, which indicated that LF-N2 has potential use as a probiotic due to its gastric injury treatment effects.
PubMed: 35299759
DOI: 10.3389/fnut.2022.840566 -
Biomolecules Apr 2024Motilin is a gastrointestinal hormone that is mainly produced in the duodenum of mammals, and it is responsible for regulating appetite. However, the role and expression...
Motilin is a gastrointestinal hormone that is mainly produced in the duodenum of mammals, and it is responsible for regulating appetite. However, the role and expression of motilin are poorly understood during starvation and the weaning stage, which is of great importance in the seeding cultivation of fish. In this study, the sequences of Yangtze sturgeon ( ()) motilin receptor () were cloned and characterized. The results of tissue expression showed that by contrast with mammals, mRNA was richly expressed in the brain, whereas was highly expressed in the stomach, duodenum, and brain. Weaning from a natural diet of to commercial feed significantly promoted the expression of in the brain during the period from day 1 to day 10, and after re-feeding with the change in expression of was partially reversed. Similarly, it was revealed that fasting increased the expression of in the brain (3 h, 6 h) and duodenum (3 h), and the expression of in the brain (1 h) in a time-dependent manner. Furthermore, it was observed that peripheral injection of motilin-NH increased food intake and the filling index of the digestive tract in the Yangtze sturgeon, which was accompanied by the changes of and appetite factors expression in the brain (, , , and ) and stomach (). These results indicate that motilin acts as an indicator of nutritional status, and also serves as a novel orexigenic factor that stimulates food intake in . This study lays a strong foundation for the application of as a biomarker in the estimation of hunger in juvenile during the weaning phase, and enhances the understanding of the role of motilin as a novel regulator of feeding in fish.
Topics: Animals; Brain; Feeding Behavior; Fish Proteins; Fishes; Motilin; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide
PubMed: 38672450
DOI: 10.3390/biom14040433