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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 -
Journal of Agricultural and Food... Apr 2018This study was to probe the effects of bacterial cellulose (BC) on diphenoxylate-induced constipation in rats. Administration with BC at 500 mg/kg of body weight in...
This study was to probe the effects of bacterial cellulose (BC) on diphenoxylate-induced constipation in rats. Administration with BC at 500 mg/kg of body weight in diphenoxylate-induced constipation rats distinctly improved the carmine propulsion rate (83.5 ± 5.2%), shortened the defecating time of the first red feces (249.0 ± 23.3 min), and increased the weight of carmine red feces within 5 h (2.7 ± 1.3 g). The levels of aquaporins (AQP-2, AQP-3, and AQP-4) and inhibitory neurotransmitters (nitric oxide, nitric oxide synthetase, vasoactive intestinal peptide, and arginine vasopressin) in the BC-treated groups reduced by 31.9-40.0% ( p < 0.01) and 21.1-67.7% ( p < 0.01) compared to those in the constipation group, respectively. However, the secretion of excitability neurotransmitters (substance P and motilin) in the BC-treated groups was increased by 20.0-39.9% ( p < 0.01). The activities of ATPases in the colon of constipation rats were significantly weakened by BC administration ( p < 0.01). Histological morphology of the colon showed that BC supplementation could effectively increase the length of villus cells and the thickness of colonic mucosa and muscle ( p < 0.01). Moreover, BC supplementation could protect colonic smooth muscle cells against apoptosis. All of the findings suggest that BC supplementation effectively relieves constipation in rats and BC would be used as a great promising dietary fiber for alleviating constipation.
Topics: Acetobacteraceae; Animals; Aquaporins; Cellulose; Constipation; Defecation; Diphenoxylate; Humans; Intestinal Mucosa; Male; Motilin; Rats; Rats, Sprague-Dawley; Substance P
PubMed: 29627986
DOI: 10.1021/acs.jafc.8b00385 -
Journal of Ethnopharmacology Feb 2024Functional constipation (FC), characterized by chronic constipation, significantly impacts physiological function and induces psychological stress in patients. However,...
HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE
Functional constipation (FC), characterized by chronic constipation, significantly impacts physiological function and induces psychological stress in patients. However, current clinical treatment options for FC are currently limited. Cistanche deserticola, a traditional Chinese medicine that promotes intestinal moisture and bowel relaxation, contains cistanche total alditol extract (CTAE) as its primary active extract. However, the production of CTAE, its overall efficacy, and potential mechanisms for treating FC have yet to been investigated.
AIM OF THE STUDY
This study aimed to reveal the overall efficacy and potential mechanism of action of CTAE in rats with FC using a combination of stable preparation, pharmacodynamics, non-targeted metabolomics, bile acid metabolomics, and western blotting.
MATERIALS AND METHODS
Fourteen batches of CTAE underwent quality testing. A rat model of FC was developed using diphenoxylate tablets. The comprehensive pharmacodynamic effects of CTAE on FC were evaluated using fecal characteristics (wet weight, dry weight, and water content), intestinal transmission (colonic EMG amplitude, colonic EMG frequency, propulsion length, and propulsion rate), serum and colon biochemical indicators, distribution of interstitial cells of Cajal (ICC), and pathological examination. Non-targeted metabolomics was performed to assess the changes in endogenous metabolite profiles induced by CTAE. Bile acid metabolomics and western blotting analyses were employed to validate the potential mechanisms of action of CTAE.
RESULTS
CTAE, with a total content of betaine, mannitol, D-fructose, glucose, and sucrose of (75.67 ± 3.73) %, significantly enhanced intestinal transit, regulated neurotransmitters, increased the expression of c-kit in ICC, and alleviated intestinal inflammation in rats with FC. Non-targeted metabolomics revealed that CTAE significantly alleviated FC-induced metabolic disorders, mainly the biosynthesis of primary bile acids. Targeted metabolomic analysis confirmed that CTAE regulated FC-induced bile acid disorders. Western-blotting results confirmed that CTAE increased the expression of CYP8B1, FGF15, TGR5, and FXR, thereby modulating bile acid synthesis and enterohepatic circulation.
CONCLUSION
CTAE demonstrates significant therapeutic effects on FC, primarily through the regulation of bile acid synthesis and enterohepatic circulation. These findings provide a promising foundation for the development and clinical application of novel CATE-based drugs.
Topics: Humans; Rats; Animals; Cistanche; Sugar Alcohols; Constipation; Intestines; Bile Acids and Salts
PubMed: 37967778
DOI: 10.1016/j.jep.2023.117420 -
American Journal of Translational... 2022Constipation is a common gastrointestinal problem worldwide. Its impact on health can range from an unpleasant problem to being seriously troublesome. When lifestyle... (Review)
Review
Constipation is a common gastrointestinal problem worldwide. Its impact on health can range from an unpleasant problem to being seriously troublesome. When lifestyle modification fails to deal with constipation, laxatives are the mainstay of therapy. There are several types of laxatives currently available; however, there still remains a need for better laxatives because certain currently available laxatives are not appropriate for or accessible to some patients. Preclinical experiments to study the laxative potential of substances/products of interest are vital to improving that situation. The selection of appropriate experimental models for assessing the laxative activities of substances/products under investigation is crucial to achieving valid and meaningful results. This article provides a scoping review of the literature, outlining, and summarizing models currently being used in preclinical experiments assessing the laxative activities of substances/products under investigation. The review includes both screening models, e.g., the isolated organ bath system, fecal assessment and intestinal transit assay, and confirmation models, e.g., constipation models. Chemical substances/drugs used to induce constipation in constipation models, e.g., loperamide, diphenoxylate, montmorillonite, and clonidine, as well as standard laxative agents used as a positive control in experimental models, e.g., bisacodyl, carbachol, lactulose, sodium picosulfate, castor oil, phenolphthalein, and yohimbine, are described in detail. The purpose of this article is to assist researchers in the design and implementation of preclinical experimental models for assessing laxative activities of substances/products under investigation to achieve valid and meaningful preclinical results prior to experimentation in humans.
PubMed: 35273679
DOI: No ID Found -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Nov 2022To investigate the effects of Mijian Daotong Bowel Suppository (MJDs) on the compound diphenoxylate induced constipation model of male rats and its mechanisms. Sixty...
To investigate the effects of Mijian Daotong Bowel Suppository (MJDs) on the compound diphenoxylate induced constipation model of male rats and its mechanisms. Sixty SD male rats were randomly divided into blank group, model group, positive group and MJDs group. The constipation model was established by using compound diphenoxylate gavage. The rats in blank group and model group were treated with saline by enema, the rats in positive group and MJDs group were given Kaisailu and honey decoction laxative suppository by enema, respectively, once a day for 10 days. The body weight, fecal water content, gastric emptying rate (GER) and carbon ink propulsion rate (CIPR) of rats were observed during modeling and administration. The effects of MJDs on the pathological changes of colon tissue in constipation rats were investigated by hematoxylin-eosin (HE) staining. The effect of MJDs on 5-hydroxytryptamine (5-HT) in the colon of constipation rats was investigated by ELISA kit. The effects of MJDs on the expressions of aquaporins 3 (AQP3) and aquaporins 4 (AQP4) in the colon of constipation rats were detected by immunohistochemistry. After 10 days of administration, compared with the blank group, the body weight, fecal water content, carbon ink propulsion rate and colon 5-HT content in the model group were decreased significantly, while the expression levels of AQP3 and AQP4 in the colon were increased significantly (<0.05, <0.01). Compared with the model group, the fecal water content and colon 5-HT content in the positive group were increased significantly, and the expressions of AQP3 and AQP4 in the colon were decreased significantly. The body weight, fecal water content and colon 5-HT content in the MJDs group were increased significantly, and the expressions of AQP3 and AQP4 was decreased significantly (<0.05, <0.01). Compared with the positive group, the fecal water content of the MJDs group was decreased significantly, and the expressions of AQP3 and AQP4 in the colon of the MJDs group was decreased significantly (<0.05, <0.01). Gastric emptying rate was not statistically significant difference between the groups. MJDs has good therapeutic effects on constipation, and its mechanisms may be related to up-regulating the content of 5-HT in the colon and down-regulating the expressions of AQP3 and AQP4 in the colon.
Topics: Male; Animals; Rats; Laxatives; Diphenoxylate; Serotonin; Constipation; Body Weight; Carbon; Aquaporins
PubMed: 37308434
DOI: 10.12047/j.cjap.6337.2022.141 -
The Journal of Community and Supportive... Jan 2015Cholinergic syndrome is a well established acute adverse reaction associated with irinotecan. Cholinergic side effects can be ameliorated or prevented with...
BACKGROUND
Cholinergic syndrome is a well established acute adverse reaction associated with irinotecan. Cholinergic side effects can be ameliorated or prevented with anticholinergic agents. To date, no formal studies have compared atropine-diphenoxylate and hyoscyamine as premedications for prophylaxis of the cholinergic syndrome with irinotecan infusion.
OBJECTIVES
To compare the incidence of cholinergic syndrome with irinotecan using atropine-diphenoxylate or hyoscyamine as premedication.
METHODS
We conducted a retrospective, single-center, nonrandomized, cohort study of adult patients treated with atropine-diphenoxylate or hyoscyamine as premedication before receiving irinotecan. For all irinotecan infusions, intravenous atropine was administered for patients experiencing any cholinergic reaction.
RESULTS
A total of 532 irinotecan cycles (354 cycles for atropine-diphenoxylate group; 178 cycles for hyoscyamine group) were analyzed in 80 patients. Overall incidence of cholinergic syndrome did not differ between atropine-diphenoxylate (8.2%) and hyoscyamine (9.0%) groups (P = .76). The incidence of cholinergic syndrome after the £rst cycle of irinotecan was similar between the 2 arms, atropine-diphenoxylate (14.6%) and hyoscyamine (10.7%), with P = .74. The most common cholinergic symptoms documented were abdominal pain or cramping, and diarrhea.
LIMITATIONS
This study was subjected to vulnerabilities to bias and random error because of its observational retrospective design and small number of participants.
CONCLUSIONS
Lack of difference in the incidence of cholinergic syndrome observed in irinotecan-treated patients suggests atropinediphenoxylate and hyoscyamine may both be effective prophylactic options. The findings support the need for a larger, randomized study to assess and compare these agents with other potential premedications such as scopolamine and atropine in prevention of irinotecan-related cholinergic syndrome.
PubMed: 25839059
DOI: 10.12788/jcso.0099 -
Medeniyet Medical Journal Dec 2023Potentially inappropriate medications (PIM) is a crucial problem in the geriatric population. The amount of prescription and unadherence increase because of the...
OBJECTIVE
Potentially inappropriate medications (PIM) is a crucial problem in the geriatric population. The amount of prescription and unadherence increase because of the different problems encountered in cancer patients. Our aim was to evaluate the effects of PIM in patients with gastrointestinal system cancer and to investigate its relationship with chemotherapy side effects, mortality, and progression.
METHODS
This retrospective cohort study assessed 154 patients with gastrointestinal system cancer. Demographics and disease features, the presence of PIM according to the "TIME-to-STOP" criteria and baseline laboratory parameters were recorded. The effects of PIM on survival and adverse treatment events were evaluated.
RESULTS
66.9% of the cases were male and 33.1% were female. The mean age was 71.9±6.4 years. The most common side effects of chemotherapy are nausea, vomiting, kidney injury, and pain. The most frequently used prescriptions among the 98 PIMs were gliclazide, hyoscine N-butylbromide, simethicone, diphenoxylate atropine, and thiocolchicoside. PIM was detected in 68.1% of the participants. Chemotherapy side effects were more common in PIM group (p<0.001, odds ratio =5.6). PIM had no effect on mortality. Factors associated with mortality were age, stage, albumin, creatinine, operation history, and progression. A significant relationship was found between age, cancer stage, albumin, creatinine, operation history, and PIM in the regression model. There was no relationship between PIM and progression-free survival.
CONCLUSION
Chemotherapy toxicity may increase with PIM detected on diagnosis. We suggest that PIM is an important factor in predicting the side effects of chemotherapy and minimizing the adverse effects.
PubMed: 38148726
DOI: 10.4274/MMJ.galenos.2023.03063 -
British Journal of Pharmacology Feb 2017
Topics: Amides; Angiotensin-Converting Enzyme Inhibitors; Atropine; Central Nervous System; Diphenoxylate; Drug Combinations; History, 20th Century; History, 21st Century; Humans; Peptides; Peptidyl-Dipeptidase A
PubMed: 28116748
DOI: 10.1111/bph.13683 -
Frontiers in Nutrition 2022Foxtail millet () has a long history of treating gastrointestinal ailments in China; however, little is known about the functional mechanism driving its therapeutic...
Foxtail millet () has a long history of treating gastrointestinal ailments in China; however, little is known about the functional mechanism driving its therapeutic effects. The primary edible form of millet is porridge. This study investigates the effects of millet porridge on diphenoxylate-induced constipation and intestinal microflora in mice. Fifty mice were randomly divided into five groups: normal control group, constipation model group, and low-dose, medium-dose, and high-dose millet porridge groups. After 14 days of millet porridge gavage, constipation was induced and measured. The results showed that millet porridge prevented constipation by increasing the water content of feces, shortened the time of the first melena defecation, promoted gastric emptying, and improved the rate of gastrointestinal propulsion. Millet porridge also dose-dependently increased levels of and and decreased levels of , , and in the intestine. These results show that millet porridge could accelerate intestinal motility and change the proportions of intestinal flora and that it has a potent prebiotic effect.
PubMed: 36071942
DOI: 10.3389/fnut.2022.965687 -
Journal of Clinical Medicine Mar 2023In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid... (Review)
Review
In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid effects on gut function in chronic diarrhea. PubMed and Embase were searched regarding effects of opioid agonists on the gastrointestinal tract in humans with chronic or experimentally induced diarrhea. A total of 1472 relevant articles were identified and, after thorough evaluation, 11 clinical trials were included. Generally, studies reported a reduction in stool frequency and an increase in transit time during treatment with the opioid receptor agonists loperamide, asimadoline, casokefamide, and codeine compared with placebo. Loperamide and diphenoxylate significantly improved stool consistency compared with placebo, whereas asimadoline showed no such effects. Compared with placebo, loperamide treatment caused less abdominal pain and urgency. Asimadoline showed no significant subjective improvements, but fedotozine was superior to placebo in reducing abdominal pain and bloating in selected patients. Only two relevant studies were published within the last 20 years, and standardized endpoint measures are lacking. Most trials included few participants, and further evidence is needed from larger, prospective studies. Likewise, consensus is needed to standardize endpoints for stool frequency, transit time, and consistency to conduct future meta-analyses on opioids in management of chronic idiopathic diarrhea.
PubMed: 37048572
DOI: 10.3390/jcm12072488