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Experimental and Therapeutic Medicine May 2023Functional constipation (FC), a common symptom that is primarily associated with intestinal motility dysfunction, is a common problem worldwide. Arctiin (Arc) is a...
Functional constipation (FC), a common symptom that is primarily associated with intestinal motility dysfunction, is a common problem worldwide. Arctiin (Arc) is a lignan glycoside isolated from the Chinese herbal medicine , which is a health food in China. The present study aimed to evaluate the laxative effects of Arc against FC in mice. A model of FC induced by loperamide (5 mg/kg) was established in male Institute of Cancer Research (ICR) mice. Arc was administered at a dose of 100 mg/kg as a protective agent. The faecal status, intestinal motility and histological analyses were evaluated. Furthermore, the levels of gastrointestinal motility-associated neurotransmitters, such as motilin (MTL), nitric oxide (NO), and brain-derived neurotrophic factor (BDNF) and the protective effect of Arc on interstitial cells of Cajal (ICC) were assessed. Arc treatment reversed the loperamide-induced reduction in faecal number and water content and the intestinal transit ratio in ICR mice. Histological analysis confirmed that Arc administration mitigated colonic injury. Moreover, Arc treatment increased levels of motilin and brain-derived neurotrophic factor while decreasing nitric oxide levels and ICC injury in the colon of FC mice. Arc decreased inflammation induction and aquaporin expression levels. Owing to its pro-intestinal motility property, Arc was shown to have a protective effect against FC and may thus serve as a promising therapeutic strategy for the management of FC.
PubMed: 37090075
DOI: 10.3892/etm.2023.11898 -
Upsala Journal of Medical Sciences 2015A 57-year old man with low-back pain was found to have a 3 × 3 × 3 cm presacral neuroendocrine tumour (NET) with widespread metastases, mainly to the skeleton. His... (Review)
Review
BACKGROUND
A 57-year old man with low-back pain was found to have a 3 × 3 × 3 cm presacral neuroendocrine tumour (NET) with widespread metastases, mainly to the skeleton. His neoplastic disease responded well to peptide receptor radionuclide therapy (PRRT) with the radiotagged somatostatin agonist (177)Lu-DOTATATE. During almost 10 years he was fit for a normal life. He succumbed to an intraspinal dissemination.
PROCEDURES
A resection of the rectum, with a non-radical excision of the adjacent NET, was made. In addition to computerized tomography (CT), receptor positron emission tomography (PET) with (68)Ga-labelled somatostatin analogues was used.
OBSERVATIONS
The NET showed the growth pattern and immunoprofile of a G2 carcinoid. A majority cell population displayed immunoreactivity to ghrelin, exceptionally with co-immunoreactivity to motilin. Somatostatin receptor scintigraphy and (68)Ga-DOTATATE PET-CT demonstrated uptake in the metastatic lesions. High serum concentrations of total (desacyl-)ghrelin were found with fluctuations reflecting the severity of the symptoms. In contrast, the concentrations of active (acyl-)ghrelin were consistently low, as were those of chromogranin A (CgA).
CONCLUSIONS
Neoplastically transformed ghrelin cells can release large amounts of desacyl-ghrelin, evoking an array of non-specific clinical symptoms. Despite an early dissemination to the skeleton, a ghrelinoma can be compatible with longevity after adequate radiotherapy.
Topics: Biopsy, Needle; Carcinoma, Neuroendocrine; Disease Progression; Fatal Outcome; Ghrelin; Humans; Immunohistochemistry; Low Back Pain; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Neoplasms, Multiple Primary; Positron-Emission Tomography; Rectal Neoplasms; Sacrococcygeal Region; Spinal Neoplasms
PubMed: 26095011
DOI: 10.3109/03009734.2015.1054453 -
Medicine Sep 2018This study aims to investigate the relationship between gastrointestinal dysfunction (GD) and cirrhosis severity in cirrhotic patients, to provide evidences for the... (Observational Study)
Observational Study
This study aims to investigate the relationship between gastrointestinal dysfunction (GD) and cirrhosis severity in cirrhotic patients, to provide evidences for the prevention and treatment of GD in cirrhotic patients.A total of 95 cirrhotic inpatients and outpatients, who were treated in the Department of Gastroenterology of Xinqu Hospital of the First Affiliated Hospital of Henan University of Science and Technology, were enrolled in the present study, and assigned as the experimental group (cirrhosis group). According to Child-Pugh classification, these patients were divided into 3 groups: group A (n = 45), group B (n = 23), and group C (n = 27). Forty healthy adults who received health check-ups during the same period served as the control group. The gastrointestinal (GI) symptoms of cirrhotic patients were scored, and the fasting serum gastrin (GAS), motilin (MTL), and vasoactive intestinal peptide (VIP) levels were measured in all subjects.The potential correlations of GI symptom scores of patients in these cirrhosis groups with GI hormone levels and cirrhosis severity were analyzed. In cirrhotic patients, the GI symptom scores significantly increased. Furthermore, the symptom scores gradually increased along with the aggravation of liver damage. Moreover, serum GAS and VIP levels were significantly higher in the cirrhosis groups than in the control group, whereas MTL levels were significantly lower. These changes were significantly correlated with cirrhosis severity. The linear correlation analysis revealed that the GI symptom score was positively correlated with GAS and VIP levels, and negatively correlated with MTL level. In addition, the linear correlation analysis revealed that GI symptom score and GAS and VIP levels were positively correlated with cirrhosis severity, whereas MTL level was negatively correlated with cirrhosis severity.Cirrhotic patients have more obvious GI symptoms and higher GI hormone levels, which are closely correlated with the progression of liver cirrhosis and the degree of liver function damage.
Topics: Adult; Aged; Biomarkers; Disease Progression; Female; Gastrins; Gastrointestinal Diseases; Humans; Liver Cirrhosis; Male; Middle Aged; Motilin; Severity of Illness Index; Vasoactive Intestinal Peptide; Young Adult
PubMed: 30212936
DOI: 10.1097/MD.0000000000012070 -
Frontiers in Pharmacology 2023Motilin (MLN) is a gastrointestinal (GI) hormone produced in the upper small intestine. Its most well understood function is to participate in Phase III of the...
Motilin (MLN) is a gastrointestinal (GI) hormone produced in the upper small intestine. Its most well understood function is to participate in Phase III of the migrating myoelectric complex component of GI motility. Changes in MLN availability are associated with GI diseases such as gastroesophageal reflux disease and functional dyspepsia. Furthermore, herbal medicines have been used for several years to treat various GI disorders. We systematically reviewed clinical and animal studies on how herbal medicine affects the modulation of MLN and subsequently brings the therapeutic effects mainly focused on GI function. We searched the PubMed, Embase, Cochrane, and Web of Science databases to collect all articles published until 30 July 2023, that reported the measurement of plasma MLN levels in human randomized controlled trials and herbal medicine studies. The collected characteristics of the articles included the name and ingredients of the herbal medicine, physiological and symptomatic changes after administering the herbal medicine, changes in plasma MLN levels, key findings, and mechanisms of action. The frequency patterns (FPs) of botanical drug use and their correlations were investigated using an FP growth algorithm. Nine clinical studies with 1,308 participants and 20 animal studies were included in the final analyses. Herbal medicines in clinical studies have shown therapeutic effects in association with increased levels of MLN, including GI motility regulation and symptom improvement. Herbal medicines have also shown anti-stress, anti-tumor, and anti-inflammatory effects . Various biochemical markers may correlate with MLN levels. Markers may have a positive correlation with plasma MLN levels included ghrelin, acetylcholine, and secretin, whereas a negative correlation included triglycerides and prostaglandin E. Markers, such as gastrin and somatostatin, did not show any correlation with plasma MLN levels. Based on the FP growth algorithm, and were the most frequently used species. Herbal medicine may have therapeutic effects mainly on GI symptoms with involvement of MLN regulation and may be considered as an alternative option for the treatment of GI diseases. Further studies with more solid evidence are needed to confirm the efficacy and mechanisms of action of herbal medicines. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=443244, identifier CRD42023443244.
PubMed: 38161695
DOI: 10.3389/fphar.2023.1286333 -
Computational and Mathematical Methods... 2022Functional dyspepsia (FD) is a common digestive system disease, and probiotics in the treatment of FD have a good curative effect. Patients with gastrointestinal...
Functional dyspepsia (FD) is a common digestive system disease, and probiotics in the treatment of FD have a good curative effect. Patients with gastrointestinal diseases often show a poor response to traditional drug treatments and suffer from adverse reactions. Kvass can be used as a functional drink without side effects to improve the symptoms of FD patients. The results showed that compared with those of the model group, the body weight and food intake of the treatment group were significantly increased ( < 0.05), and the gastric residual rate of the treatment group was significantly decreased ( < 0.05); the amount of pepsin in the treatment group was significantly higher than that in the model group ( < 0.05); a high dose of Kvass could increase the contents of ghrelin, motilin (MTL), and gastrin (GAS) in the plasma and decrease the contents of vasoactive intestinal peptide (VIP) in the plasma; the contents of ghrelin, MTL, and GAS in the gastric antrum were also increased in the high-dose group. Kvass beverage can significantly improve the gastrointestinal function of rats, which may be because it can improve the contents of ghrelin, MTL, GAS, and VIP in both the serum and gastric antrum by regulating the expression of short-chain fatty acids in the colon.
Topics: Animals; Dyspepsia; Gastrointestinal Motility; Ghrelin; Motilin; Rats; Stomach; Vasoactive Intestinal Peptide
PubMed: 35799630
DOI: 10.1155/2022/5169892 -
Frontiers in Nutrition 2022Slow transit constipation (STC) is a common disorder in the digestive system. This study aimed to evaluate the effects of stachyose (ST) and Furu 2019 () alone or...
INTRODUCTION
Slow transit constipation (STC) is a common disorder in the digestive system. This study aimed to evaluate the effects of stachyose (ST) and Furu 2019 () alone or combined on diphenoxylate-induced constipation and explore the underlying mechanisms using a mouse model.
METHODS
ICR mice were randomly divided into five groups. The normal and constipation model groups were intragastrically administrated with PBS. The ST, , and synbiotic groups were intragastrically administrated with ST (1.5 g/kg body weight), alive (3 × 10 CFU/mouse), or ST + (1.5 g/kg plus 3 × 10 CFU/mouse), respectively. After 21 days of intervention, all mice except the normal mice were intragastrically administrated with diphenoxylate (10 mg/kg body weight). Defecation indexes, constipation-related intestinal factors, serum neurotransmitters, hormone levels, short-chain fatty acids (SCFAs), and intestinal microbiota were measured.
RESULTS
Our results showed that three interventions with ST, , and synbiotic combination (ST + . sakei) all alleviated constipation, and synbiotic intervention was superior to ST or alone in some defecation indicators. The RT-PCR and immunohistochemical experiment showed that all three interventions relieved constipation by affecting aquaporins (AQP4 and AQP8), interstitial cells of Cajal (SCF and c-Kit), glial cell-derived neurotrophic factor (GDNF), and Nitric Oxide Synthase (NOS). The three interventions exhibited a different ability to increase the serum excitatory neurotransmitters and hormones (5-hydroxytryptamine, substance P, motilin), and reduce the serum inhibitory neurotransmitters (vasoactive intestinal peptide, endothelin). The result of 16S rDNA sequencing of feces showed that synbiotic intervention significantly increased the relative abundance of beneficial bacteria such as , and regulated the gut microbes of STC mice. In conclusion, oral administration of ST or alone or combined are all effective to relieve constipation and the symbiotic use may have a promising preventive effect on STC.
PubMed: 36687730
DOI: 10.3389/fnut.2022.1039403 -
Neurochemistry International Mar 2021The localization of bacterial components and/or metabolites in the central nervous system may elicit neuroinflammation and/or neurodegeneration. Helicobacter pylori (a... (Review)
Review
The localization of bacterial components and/or metabolites in the central nervous system may elicit neuroinflammation and/or neurodegeneration. Helicobacter pylori (a non-commensal symbiotic gastrointestinal pathogen) infection and its related metabolic syndrome have been implicated in the pathogenesis of gastrointestinal tract and central nervous system disorders, thus medications affecting the nervous system - gastrointestinal tract may shape the potential of Helicobacter pylori infection to trigger these pathologies. Helicobacter pylori associated metabolic syndrome, by impairing gut motility and promoting bacterial overgrowth and translocation, might lead to brain pathologies. Trimebutine maleate is a prokinetic drug that hastens gastric emptying, by inducing the release of gastrointestinal agents such as motilin and gastrin. Likewise, it appears to protect against inflammatory signal pathways, involved in inflammatory disorders including brain pathologies. Trimebutine maleate also acts as an antimicrobial agent and exerts opioid agonist effect. This study aimed to investigate a hypothesis regarding the recent advances in exploring the potential role of gastrointestinal tract microbiota dysbiosis-related metabolic syndrome and Helicobacter pylori in the pathogenesis of gastrointestinal tract and brain diseases. We hereby proposed a possible neuroprotective role for trimebutine maleate by altering the dynamics of the gut-brain axis interaction, thus suggesting an additional effect of trimebutine maleate on Helicobacter pylori eradication regimens against these pathologies.
Topics: Brain Diseases; Dysbiosis; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Microbiome; Helicobacter Infections; Helicobacter pylori; Humans; Treatment Outcome; Trimebutine
PubMed: 33535070
DOI: 10.1016/j.neuint.2020.104938 -
PloS One 2019Motilin is a gastrointestinal peptide hormone that stimulates gastrointestinal motility. Motilin is produced primarily in the duodenum and jejunum. Motilin receptors...
Motilin is a gastrointestinal peptide hormone that stimulates gastrointestinal motility. Motilin is produced primarily in the duodenum and jejunum. Motilin receptors (MTLRs) are G protein-coupled receptors that may represent a clinically useful pharmacological target as they can be activated by erythromycin. The functions of motilin are highly species-dependent and remain poorly understood. As a functional motilin system is absent in rodents such as rats and mice, these species are not commonly used for basic studies. In this study, we examine the usefulness of human MTLR-overexpressing transgenic (hMTLR-Tg) mice by identifying the mechanisms of the gastric motor response to human motilin and erythromycin. The distribution of hMTLR was examined immunohistochemically in male wild-type (WT) and hMTLR-Tg mice. The contractile response of gastric strips was measured isometrically in an organ bath, while gastric emptying was determined using phenol red. hMTLR expression was abundant in the gastric smooth muscle layer. Interestingly, higher levels of hMTLR expression were observed in the myenteric plexus of hMTLR-Tg mice but not WT mice. hMTLR was not co-localized with vesicular acetylcholine transporter, a marker of cholinergic neurons in the myenteric plexus. Treatment with human motilin and erythromycin caused concentration-dependent contraction of gastric strips obtained from hMTLR-Tg mice but not from WT mice. The contractile response to human motilin and erythromycin in hMTLR-Tg mice was affected by neither atropine nor tetrodotoxin and was totally absent in Ca2+-free conditions. Furthermore, intraperitoneal injection of erythromycin significantly promoted gastric emptying in hMTLR-Tg mice but not in WT mice. Human motilin and erythromycin stimulate gastric smooth muscle contraction in hMTLR-Tg mice. This action is mediated by direct contraction of smooth muscle via the influx of extracellular Ca2+. Thus, hMTLR-Tg mice may be useful for the evaluation of MTLR agonists as gastric prokinetic agents.
Topics: Animals; Calcium; Cations, Divalent; Cholinergic Neurons; Erythromycin; Gastrointestinal Motility; Gene Expression; Humans; Male; Mice, Inbred C57BL; Mice, Transgenic; Motilin; Muscle Contraction; Muscle, Smooth; Myenteric Plexus; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Stomach; Tissue Culture Techniques
PubMed: 30789939
DOI: 10.1371/journal.pone.0205939 -
PloS One 2015Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect...
Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastric acid secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. We first established a gastric lumen-perfusion system in the suncus and confirmed that intravenous (i.v.) administration of histamine (1 mg/kg body weight) stimulated acid secretion. Motilin (0.1, 1.0, and 10 μg/kg BW) stimulated the acid output in a dose-dependent manner in suncus, whereas ghrelin (0.1, 1.0, and 10 μg/kg BW) alone did not induce acid output. Furthermore, in comparison with the vehicle administration, the co-administration of low-dose (1 μg/kg BW) motilin and ghrelin significantly stimulated gastric acid secretion, whereas either motilin (1 μg/kg BW) or ghrelin (1 μg/kg BW) alone did not significantly induce gastric acid secretion. This indicates an additive role of ghrelin in motilin-induced gastric acid secretion. We then investigated the pathways of motilin/motilin and ghrelin-stimulated acid secretion using receptor antagonists. Treatment with YM 022 (a CCK-B receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist) had no effect on motilin or motilin-ghrelin co-administration-induced acid output. In contrast, famotidine (a histamine H2 receptor antagonist) completely inhibited motilin-stimulated acid secretion and co-administration of motilin and ghrelin induced gastric acid output. This is the first report demonstrating that motilin stimulates gastric secretion in mammals. Our results also suggest that motilin and co-administration of motilin and ghrelin stimulate gastric acid secretion via the histamine-mediated pathway in suncus.
Topics: Animals; Anti-Ulcer Agents; Biological Transport; Famotidine; Female; Gastric Acid; Gastric Mucosa; Gastrointestinal Motility; Ghrelin; Male; Models, Animal; Motilin; Shrews; Stomach; Up-Regulation
PubMed: 26115342
DOI: 10.1371/journal.pone.0131554 -
Cell Biology International Jan 2020Motilin, a 22-amino-acid peptide produced in the upper small intestine, induces strong gastric contraction in fasted state. In many rodents, motilin and its cognate...
Motilin, a 22-amino-acid peptide produced in the upper small intestine, induces strong gastric contraction in fasted state. In many rodents, motilin and its cognate receptors exist as pseudogenes, which has delayed motilin research in the past decades. Recently, the house musk shrew (Suncus murinus) was developed as a useful model for studying motilin and gastrointestinal motility. However, due to a lack of motilin-producing cell lines and difficulties in culturing small intestinal cells, the regulatory mechanisms of motilin secretion and its messenger RNA (mRNA) transcription have remained largely unclear. In this study, we generated small intestinal organoids from S. murinus for the first time. Using methods similar to mouse organoid generation, we found crypt-like budding structures 3 days after isolating intestinal tissues. The organoids grew gradually with time. In addition, the generated organoids were able to be passaged and maintained for 6 months or longer. Motilin messenger RNA (mRNA) and immunopositive cells were observed in both S. murinus intestinal organoids and primary tissues. This is the first report of intestinal organoids in S. murinus, and our results suggest that S. murinus intestinal organoids could be useful for analyzing motilin secretion and transcription.
PubMed: 31293061
DOI: 10.1002/cbin.11201