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1.
Food Funct ; 15(11): 6118-6133, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38764333

RESUMO

Constipation is a major gastrointestinal (GI) symptom worldwide, with diverse causes of formation, and requires effective and safe therapeutic measures. In the present study, we used loperamide hydrochloride to establish a constipation model and assessed the effect of Bifidobacterium on constipation and its possible mechanism of relief. The results showed that B. longum S3 exerted a constipation-relieving effect primarily by improving the gut microbiota, enriching genera including Lactobacillus, Alistipes, and Ruminococcaceae UCG-007, and decreasing the bacteria Lachnospiraceae NK4B4 group. These changes may thereby increase acetic acid and stearic acid (C18:0) levels, which significantly increase the expression levels of ZO-1 and MUC-2, repair intestinal barrier damage and reduce inflammation (IL-6). Furthermore, it also inhibited oxidative stress levels (SOD and CAT), decreased the expression of water channel proteins (AQP4 and AQP8), significantly elevated the Gas, 5-HT, PGE2, and Ach levels, and reduced nNOS and VIP levels to improve the intestinal luminal transit time and fecal water content. Collectively, these changes resulted in the alleviation of constipation.


Assuntos
Ácido Acético , Bifidobacterium longum , Constipação Intestinal , Microbioma Gastrointestinal , Loperamida , Probióticos , Ácidos Esteáricos , Loperamida/efeitos adversos , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/metabolismo , Animais , Camundongos , Probióticos/farmacologia , Ácidos Esteáricos/metabolismo , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Modelos Animais de Doenças , Intestinos/microbiologia
2.
Benef Microbes ; 15(3): 311-329, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38688519

RESUMO

Probiotics exert beneficial effects by regulating the intestinal microbiota, metabolism, immune function and other ways of their host. Patients with constipation, a common gastrointestinal disorder, experience disturbances in their intestinal microbiota. In the present study, we investigated the effectiveness of two microbial ecological agents (postbiotic extract PE0401 and a combination of postbiotic extract PE0401 and Lacticaseibacillus paracasei CCFM 2711) in regulating the makeup of the intestinal microbiota and alleviating loperamide hydrochloride-induced constipation in mice. We also preliminarily explored the mechanism underlying their effects. Both microbial ecological agents increased the abundance of the beneficial bacteria Lactobacilli and Bifidobacterium after administration and were able to relieve constipation. However, the degree of improvement in constipation symptoms varied depending on the makeup of the supplement. The postbiotic extract PE0401 increased peristalsis time and improved faecal properties throughout the intestinal tract of the host. PE0401 relieved constipation, possibly by modulating the levels of the constipation-related gastrointestinal regulatory transmitters mouse motilin, mouse vasoactive intestinal peptide, and 5-hydoxytryptamine in the intestinal tract of the host and by increasing the levels of the short-chain fatty acids (SCFAs) acetic acid, propionic acid, and isovaleric acid. It also increased the relative abundance of Lactobacillus and Bifidobacterium and reduced that of Faecalibaculum, Mucispirillum, Staphylococcus, and Lachnoclostridium, which are among the beneficial microbiota in the host intestine. Furthermore, PE0401 decreased the levels of constipation-induced host inflammatory factors. Therefore, the two microbial ecological agents can regulate the intestinal microbiota of constipation mice, and PE0401 has a stronger ability to relieve constipation.


Assuntos
Constipação Intestinal , Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Loperamida , Probióticos , Animais , Loperamida/efeitos adversos , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Camundongos , Probióticos/administração & dosagem , Probióticos/farmacologia , Probióticos/uso terapêutico , Masculino , Bifidobacterium , Lacticaseibacillus paracasei , Modelos Animais de Doenças , Lactobacillus , Motilina/metabolismo , Fezes/microbiologia , Fezes/química , Peptídeo Intestinal Vasoativo/metabolismo
3.
Geriatr Psychol Neuropsychiatr Vieil ; 22(1): 28-33, 2024 Mar 01.
Artigo em Francês | MEDLINE | ID: mdl-38573141

RESUMO

The aim was to perform a systematic review of cases published in the literature to describe the management of high-output ileostomy (HOI) in older adults. A literature search was performed in PubMed©, and Scopus© for all publications up to March 1st, 2023. Case reports and/or case series reporting data from older adults on HOI management were included. Publication year, country, sex, age, aetiology of the stomy, time from ileostomy to HOI, daily volume threshold, Treatment regimen, and effectiveness were extracted. In total, 428 studies were identified, of which 9 (describing 10 cases) were included in this review. The mean age was 69.9 ± 4.7 years. The most frequent aetiology of ileostomy was occlusion. The daily volume considered to be excessive ranged from 1 to 2 litres per 24-hour period. The main side effects of HOI were dehydration, acute renal failure, and weight loss. Loperamide was the most frequently used drug. Most studies reported that non-pharmacological therapies were also used. No death was reported in any of the studies. In all, ileostomy exposes older individuals to complications. Medical therapy with loperamide coupled with rehydration seems to be efficacious in the medium term. Multidisciplinary management is advisable, in order to increase the chances of achieving ostomy reversal as early as possible, when indicated.


Assuntos
Ileostomia , Loperamida , Humanos , Idoso
4.
Sci Rep ; 14(1): 7152, 2024 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531966

RESUMO

Constipation is a major health problem worldwide that requires effective and safe treatment options. Increasing evidence indicates that disturbances in gut microbiota may be a risk factor for constipation. Administration of lacidophilin tablets shows promising therapeutic potential in the treatment of inflammatory bowel disease owing to their immunomodulatory properties and regulation of the gut microbiota. The focus of this study was on investigating the ability of lacidophilin tablets to relieve constipation by modulating the gut microbiome. Rats with loperamide hydrochloride induced constipation were treated with lacidophilin tablets via intragastric administration for ten days. The laxative effect of lacidophilin tablets was then evaluated by investigating the regulation of intestinal microflora and the possible underlying molecular mechanism. Our results reveal that treatment with lacidophilin tablets increased the intestinal advancement rate, fecal moisture content, and colonic AQP3 protein expression. It also improved colonic microflora structure in the colonic contents of model rats mainly by increasing Akkermansia muciniphila and decreasing Clostridium_sensu_stricto_1. Transcriptome analysis indicated that treatment with lacidophilin tablets maintains the immune response in the intestine and promotes recovery of the intestinal mechanical barrier in the constipation model. Our study shows that lacidophilin tablets improve constipation, possibly by promoting Akkermansia colonization and by modulating the intestinal immune response.


Assuntos
Microbioma Gastrointestinal , Ratos , Animais , Akkermansia , Constipação Intestinal/tratamento farmacológico , Intestinos , Loperamida
5.
Anticancer Res ; 44(3): 1063-1070, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38423641

RESUMO

BACKGROUND/AIM: Osteosarcoma is an aggressive malignant bone tumor, with unfavorable outcomes in patients with metastatic and recurrent disease. To improve patient survival new treatment options are needed. By using the drug repurposing approach, which takes advantage of already approved drugs with non-oncology primary use, we investigated the activity of loperamide, a peripheral opiate receptor agonist, a drug widely used in clinical practice to treat acute non-specific and chronic diarrhea, on human osteosarcoma. MATERIALS AND METHODS: Human osteosarcoma cell lines (143B, Saos-2, HOS and MG-63) and multidrug-resistant MG-63DXR30 cells were treated with loperamide. Proliferation and cell viability were determined by viable cell count and acid phosphatase assay. Loperamide activity on cell cycle and apoptosis induction were evaluated by flow cytometry and a luminescence assay testing caspase 3/7 activity, respectively. RESULTS: Loperamide significantly inhibited cell proliferation, through alteration of cell cycle profile at G0/G1 phase and apoptotic death in human osteosarcoma cells. Furthermore, loperamide significantly inhibited the growth of multidrug-resistant osteosarcoma cells. CONCLUSION: Our findings provide new perspectives for loperamide and its therapeutic repositioning for the treatment of osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Loperamida/farmacologia , Reposicionamento de Medicamentos , Osteossarcoma/tratamento farmacológico , Bioensaio , Proliferação de Células , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Apoptose
6.
Scand J Gastroenterol ; 59(5): 543-546, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38343268

RESUMO

The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.


Chronic diarrhoea without an established cause is common.There are a small number of clinical trials, often with a limited number of patients or healthy volunteers.Treatment is often carried out on a trial-and-error basis, with considerable variation in the choice of treatment.There is a paucity of guidelines, and there is a gap in knowledge concerning treatment goals, such as the frequency, consistency and form of stool.The stepwise approach to the treatment of chronic idiopathic diarrhoea described in this article is based on clinical knowledge and experience.


Assuntos
Antidiarreicos , Diarreia , Humanos , Diarreia/tratamento farmacológico , Diarreia/etiologia , Antidiarreicos/uso terapêutico , Loperamida/uso terapêutico , Octreotida/uso terapêutico , Clonidina/uso terapêutico , Clonidina/análogos & derivados
7.
PLoS One ; 19(1): e0282769, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38265977

RESUMO

Targeted therapies have increased cancer therapy-related diarrhea (CTD) burden, with high incidence and/or severity of diarrhea for some agents that inhibit epidermal growth factor receptor and receptor tyrosine kinases. Neratinib is a pan-HER tyrosine kinase inhibitor approved for breast cancer treatment and causes severe diarrhea in >95% of patients. Crofelemer, a novel intestinal chloride ion channel modulator, is an approved antidiarrheal drug for symptomatic relief of noninfectious diarrhea in patients with HIV/AIDS receiving antiretroviral therapy. The objective of this study was to evaluate the effectiveness of crofelemer prophylaxis in reducing the incidence /severity of neratinib-induced diarrhea without concomitant administration of loperamide in female beagle dogs. A pilot study using 3 dogs determined a maximum daily tolerated dose of neratinib was between 40 and 80 mg; this dose would induce a consistent incidence/severity of diarrhea without risking severe dehydration. In the definitive study, 24 female beagle dogs (8/group) received neratinib once daily and placebo capsules (CTR) four times/day, or neratinib once daily and crofelemer 125 mg delayed-release tablets given two times (BID), or neratinib once daily and crofelemer 125 mg delayed-release tablets given four times per day (QID). Fecal scores were collected twice daily using an established canine stool scoring scale called the Purina Fecal Scoring (PFS) System. After 28 days, using analysis of covariance (ANCOVA), dogs in the CTR group had a significantly higher average number of weekly loose/watery stools (PFS of 6 or 7) when compared to either crofelemer BID (8.71±2.2 vs. 5.96±2.2, p = 0.028) or crofelemer QID (8.70±2.2 vs. 5.74±2.2, p = 0.022) treatment groups. The average number of weekly loose/watery stools were not different between the crofelemer BID and QID treatment groups (p = 0.84). This study showed that crofelemer prophylaxis reduced the incidence/severity of neratinib-associated diarrhea in female beagle dogs without the need for any loperamide administration.


Assuntos
Diarreia , Loperamida , Proantocianidinas , Quinolinas , Humanos , Feminino , Animais , Cães , Incidência , Projetos Piloto , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/veterinária
8.
J Pediatr Surg ; 59(3): 528-536, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37858392

RESUMO

BACKGROUND: Within the premature infant intestine, oxygenation and motility play key physiological roles in healthy development and disease such as necrotizing enterocolitis. To date, there are limited techniques to reliably assess these physiological functions that are also clinically feasible for critically ill infants. To address this clinical need, we hypothesized that photoacoustic imaging (PAI) can provide non-invasive assessment of intestinal tissue oxygenation and motility to characterize intestinal physiology and health. METHODS: Ultrasound and photoacoustic images were acquired in 2-day and 4-day old neonatal rats. For PAI assessment of intestinal tissue oxygenation, an inspired gas challenge was performed using hypoxic, normoxic, and hyperoxic inspired oxygen (FiO2). For intestinal motility, oral administration of ICG contrast agent was used to compare control animals to an experimental model of loperamide-induced intestinal motility inhibition. RESULTS: PAI demonstrated progressive increases in oxygen saturation (sO2) as FiO2 increased, while the pattern of oxygen localization remained relatively consistent in both 2-day and 4-day old neonatal rats. Analysis of intraluminal ICG contrast enhanced PAI images yielded a map of the motility index in control and loperamide treated rats. From PAI analysis, loperamide significantly inhibited intestinal motility, with a 32.6% decrease in intestinal motility index scores in 4-day old rats. CONCLUSION: These data establish the feasibility and application of PAI to non-invasively and quantitatively measure intestinal tissue oxygenation and motility. This proof-of-concept study is an important first step in developing and optimizing photoacoustic imaging to provide valuable insight into intestinal health and disease to improve the care of premature infants.


Assuntos
Técnicas Fotoacústicas , Humanos , Recém-Nascido , Ratos , Animais , Animais Recém-Nascidos , Técnicas Fotoacústicas/métodos , Loperamida , Oxigênio , Intestinos/diagnóstico por imagem , Biomarcadores
9.
Curr Opin Gastroenterol ; 40(3): 196-202, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37903075

RESUMO

PURPOSE OF REVIEW: Chronic diarrhea is a common disorder that interferes with normal daily activities and results in poor quality of life. Fecal urgency and incontinence often necessitate clinical consultation, but the pathophysiological mechanisms are difficult to differentiate in a clinical setting. Therefore, drugs targeting the opioid receptors, such as diphenoxylate and loperamide, are typically used, as they reduce both gut motility and secretion. RECENT FINDINGS: For severe diarrhea, morphine-containing extemporaneous opium tincture drops have recently been reprofiled to a pharmaceutical. The drug is indicated for severe diarrhea in adults when other antidiarrheals do not give sufficient fecal emptying control. The pronounced effect is due to the liquid formulation with rapid onset as a drug dissolution step is avoided. A recent prospective, noninterventional study (CLARIFY) of patients treated with opioid drops demonstrates a rapid and sustained therapeutic effect. Tolerance does not develop for the antidiarrheal effect and no dependence was observed after discontinuation. SUMMARY: This mini-review discusses the use of opium derivates for treatment of diarrhea, with an emphasis on opium drops as a new medicinal grade opium for the use as additional treatment of severe diarrhea, emphasizing its mechanism of action and evaluation of the risk-benefit ratio in the clinical setting.


Assuntos
Ópio , Qualidade de Vida , Adulto , Humanos , Ópio/uso terapêutico , Diarreia/tratamento farmacológico , Diarreia/etiologia , Antidiarreicos/uso terapêutico , Loperamida/uso terapêutico , Estudos Observacionais como Assunto
10.
J Adolesc Health ; 74(2): 392-394, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37843479

RESUMO

Loperamide, an oral over-the-counter µ-opioid receptor agonist used to treat diarrhea, acts primarily in the gut and, when used as recommended, has little to no systemic effect. At high doses, it may cause a "high" like other opioids. Recent literature describes an increasing incidence of loperamide misuse and overdose in the setting of the US opioid epidemic. In this case, we describe a 16-year-old with anorexia nervosa who developed dizziness, syncope, and constipation at the time of weight loss. These symptoms were originally attributed to malnutrition; however, after weight restoration, her symptoms worsened. She did not respond to initial management of suspected postural orthostatic tachycardia syndrome (POTS). She then developed acute urinary retention requiring hospitalization. Her symptoms were ultimately found to be caused by chronic surreptitious high-dose loperamide use. Her symptoms rapidly improved after cessation. This case illustrates the non-specific symptoms associated with loperamide misuse and the potential overlap with other common adolescent conditions. Adolescent medicine clinicians must be aware of the signs and symptoms of loperamide misuse as well as familiar with recommendations for both the management of acute complications and the treatment of the substance misuse.


Assuntos
Overdose de Drogas , Desnutrição , Feminino , Adolescente , Humanos , Loperamida/efeitos adversos , Analgésicos Opioides/uso terapêutico , Desnutrição/complicações
11.
Int J Radiat Oncol Biol Phys ; 118(3): 616-625, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37742773

RESUMO

PURPOSE: There is currently no gold standard for the management of acute radiation enteritis. We compared the efficacy and safety of Racecadotril, an anti-hypersecretory drug, versus Loperamide, an anti-motility agent, in acute radiation enteritis. METHODS AND MATERIALS: We conducted a randomized, double-masked, non-inferiority trial at a single research institute. Patients receiving curative radiation for pelvic malignancies, who developed grade 2 or 3 diarrhea (as per Common Terminology Criteria for Adverse Events, v 4.0) were included in the study. Patients in the intervention arm received Racecadotril and placebo. Patients in the control arm received Loperamide and placebo. The primary outcome was the resolution of diarrhea, 48 hours after the start of treatment. RESULTS: 162 patients were randomized between 2019 and 2022. On intention-to-treat analysis, 68/81 patients, 84%, (95% CI, 74.1%-91.2%) in the Racecadotril arm and 70/81, 86.4%, (95% CI, 77.0%-93.0%) in the Loperamide arm improved from grade 2 or 3 diarrhea to grade 1 or 0, (P= .66, χ2 test). The difference in proportion was 2.4% (95% CI: -8.5% to 13.4%). Since the upper boundary of the 95% CI crossed our non-inferiority margin of 10% (13.4%) we could not prove the non-inferiority of Racecadotril over Loperamide. Rebound constipation was more in the Loperamide arm compared to Racecadotril (17.3% vs 6.2%; P = .028) CONCLUSIONS: The non-inferiority of Racecadotril to Loperamide in acute radiation enteritis could not be demonstrated. However, Racecadotril can be the preferred drug of choice in acute radiation enteritis because Racecadotril does not affect bowel motility, achieved a high clinical success rate similar to that of Loperamide, and was associated with lesser side effects.


Assuntos
Síndrome Aguda da Radiação , Enterite , Tiorfano , Humanos , Doença Aguda , Síndrome Aguda da Radiação/tratamento farmacológico , Antidiarreicos/efeitos adversos , Diarreia/tratamento farmacológico , Diarreia/etiologia , Método Duplo-Cego , Enterite/etiologia , Enterite/induzido quimicamente , Loperamida/efeitos adversos , Tiorfano/análogos & derivados
12.
Eur J Pharmacol ; 965: 176289, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38158111

RESUMO

Piperine is a natural alkaloid that possesses a variety of therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and anticarcinogenic activities. The present study aims to assess the medicinal benefits of piperine as an anti-diarrheal agent in a chick model by utilizing in vivo and in silico techniques. For this, castor oil was administered orally to 2-day-old chicks to cause diarrhea. Bismuth subsalicylate (10 mg/kg), loperamide (3 mg/kg), and nifedipine (2.5 mg/kg) were used as positive controls, while the vehicle was utilized as a negative control. Two different doses (25 and 50 mg/kg b.w.) of the test sample (piperine) were administered orally, and the highest dose was tested with standards to investigate the synergistic activity of the test sample. In our findings, piperine prolonged the latent period while reducing the number of diarrheal feces in the experimental chicks during the monitoring period (4 h). At higher doses, piperine appears to reduce diarrheal secretion while increasing latency in chicks. Throughout the combined pharmacotherapy, piperine outperformed bismuth subsalicylate and nifedipine in terms of anti-diarrheal effects with loperamide. In molecular docking, piperine exhibited higher binding affinities towards different inflammatory enzymes such as cyclooxygenase 1 (-7.9 kcal/mol), cyclooxygenase 2 (-8.4 kcal/mol), nitric oxide synthases (-8.9 kcal/mol), and L-type calcium channel (-8.8 kcal/mol), indicating better interaction of PP with these proteins. In conclusion, piperine showed a potent anti-diarrheal effect in castor oil-induced diarrheal chicks by suppressing the inflammation and calcium ion influx induced by castor oil.


Assuntos
Alcaloides , Benzodioxóis , Bismuto , Loperamida , Compostos Organometálicos , Piperidinas , Alcamidas Poli-Insaturadas , Salicilatos , Humanos , Loperamida/efeitos adversos , Antidiarreicos/farmacologia , Óleo de Rícino/efeitos adversos , Nifedipino , Simulação de Acoplamento Molecular , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Alcaloides/efeitos adversos , Inflamação/tratamento farmacológico
13.
Mol Nutr Food Res ; 68(4): e2300615, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38152983

RESUMO

SCOPE: Torreya grandis kernel has traditionally been used to remove intestinal parasites and increases intestinal motility. However, the effect of Torreya grandis kernel oil (TKO) on constipation has not yet been investigated. Therefore, mouse model is used to investigate the effect of TKO on slow transit constipation (STC) and its possible mechanism. METHODS AND RESULTS: The effects of TKO on intestinal motility of STC mice are evaluated by fecal weight, fecal water content, colon length, defecation test, and intestinal propulsion test. The mechanism of TKO alleviating STC is explored by detecting biochemical analysis, histological analysis, western blot, qRT-PCR, immunohistochemistry, and gut microbiota analysis. The results reveal that TKO effectively promotes defecation and intestinal motility, increases the level of endothelin-1, and restores the histopathological morphology of the colon under LOP pretreatment. The expression levels of occludin, claudin-1, and zonula occludens-1 (ZO-1) mRNA and protein are up-regulated in mice receiving TKO treatment. The colonic 5-hydroxytryptamine 3R/4R (5-HT3R/5-HT4R) expressions are also increased by TKO supplementation. Additionally, TKO rescues LOP-caused disorders of the gut microbiota. CONCLUSION: Consumption of TKO is beneficial to STC recovery, and it can alleviate LOP-induced STC by up-regulating the colonic expressions of Occludin/Claudin-1/ZO-1 and 5-HT3R/5-HT4R.


Assuntos
Loperamida , Junções Íntimas , Camundongos , Animais , Loperamida/efeitos adversos , Loperamida/metabolismo , Claudina-1/genética , Claudina-1/metabolismo , Ocludina/genética , Ocludina/metabolismo , Camundongos Endogâmicos BALB C , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/metabolismo
14.
J Ethnopharmacol ; 319(Pt 3): 117378, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37923254

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Crotonis Fructus (CF), the seeds of Croton tiglium L., have been commonly used in the treatment of constipation for more than two thousand years in traditional Chinese medicine (TCM). CF needs to be processed before clinical use and Crotonis Semen Pulveratum (CP) is the processed cream of CF, which could reduce the drastic purgative action and gastrointestinal damages. However, the mechanism of CF and CP in the treatment of constipation is still unclear. AIM OF THE STUDY: This study was to evaluate the effects of CF and CP on loperamide-induced constipation and the underlying mechanism. MATERIALS AND METHODS: The chemical compositions of CF and CP were analyzed by UPLC-Q-TOF-MS. Constipated mouse model was established by loperamide (9.6 mg/kg, b.w., i.g.) for two weeks. After successful modeling, the mice were treated with CF or CP (45.5 and 136.5 mg/kg, b.w., i.g.) once a day for seven days. The physiological status, defecation indices, defecation time, and intestinal propulsion rate in mice were measured. Histopathologic examination and serum biochemical parameters were further estimated. 16S rDNA gene sequencing was carried out to characterize the effects of CF and CP on intestinal microbiome structure. Spearman correlation analysis was also performed to explore the association between gut microbiotic abundance and serum indices. RESULTS: The results verified the therapeutic effects of CF and CP on loperamide-induced constipation. CF and CP could significantly ameliorate the reduction of fecal number, fecal weight, fecal water content, and intestinal propulsion rate in mice with constipation, and the first stool defecation time was also obviously reduced. Moreover, CF and CP could regulate the secretion of gastrointestinal hormones and inflammatory factors induced by constipation. Histopathologic examination showed that CP was superior to CF in relieving pathological injury and inflammatory cell infiltration. According to 16S rDNA sequencing, CF and CP treatment could improve gut microbiota disturbance in mice with constipation and the abundance of opportunistic pathogens such as Parabacteroides, Parasutterella and Bacillus remarkably declined, while the levels of beneficial bacterial such as Candidatus_Arthromitus significantly increased. Besides, CP may play a better role in correcting the intestinal flora disorder than CF, which was more obvious in the high-dose group. In addition, phytochemical analysis revealed the presence of diterpenoids and alkaloids in CF and CP. CONCLUSIONS: CF and CP could ameliorate loperamide-induced constipation by regulating gastrointestinal hormones secretion, reducing the levels of inflammatory cytokines and improving the disturbance of gut microbiota. Moreover, CP was superior to CF in the enrichment of beneficial bacteria and reduction of harmful bacteria and histopathological damage induced by constipation, which may be related to the changes in the species and content of diterpenoids after processing. The study provides new evidence for the processing mechanism and clinical application of CF and CP.


Assuntos
Diterpenos , Hormônios Gastrointestinais , Microbioma Gastrointestinal , Camundongos , Animais , Loperamida/farmacologia , Hormônios Gastrointestinais/efeitos adversos , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , DNA Ribossômico/farmacologia , Diterpenos/farmacologia
15.
Braz. J. Pharm. Sci. (Online) ; 60: e23717, 2024. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1557201

RESUMO

Constipation is a disorder of the gastrointestinal (GI) and some of the main etiological mechanisms are directly related to changes in GI physiology. The capacity to carry out paired assessments and measure GI parameters under the influence of constipation is a relevant point in selecting a suitable methodology. We aimed to perform a non-invasive investigation of gastrointestinal motility in constipated rats using the alternating current biosusceptometry system (ACB). The animals were split into two groups: the pre-induction stage (CONTROL) and post-induction loperamide stage (LOP). We assessed GI motility parameters using the ACB system. Colon morphometric and immunohistochemical analyses were performed for biomarkers (C-kit) for interstitial cells of Cajal (ICC). Our results showed a significant increase in gastrointestinal transit in the LOP group in addition to a reduction in the dominant frequency of gastric contraction and an arrhythmic profile. A change in colonic contractility profiles was observed, indicating colonic dysmotility in the LOP group. We found a reduction in the number of biomarkers for intestinal cells of Cajal (ICC) in the LOP group. The ACB system can evaluate transit irregularities and their degrees of severity, while also supporting research into novel, safer, and more efficient treatments for constipation.


Assuntos
Animais , Masculino , Ratos , Trato Gastrointestinal/anormalidades , Motilidade Gastrointestinal , Loperamida/efeitos adversos , Constipação Intestinal/induzido quimicamente , Células Intersticiais de Cajal/classificação
16.
J Ethnopharmacol ; 322: 117637, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38135226

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Constipation is one of the most prevalent gastrointestinal tract diseases that seriously affects health-related quality of human life and requires effective treatments without side effect. The rhizome of Atractylodes macrocephala Koidz. (Compositae), called Atractylodes Macrocephala Rhizome (AMR), a commonly used traditional Chinese medicine, has been used to relieve the clinical symptoms of patients with constipation. AIM OF THE STUDY: To reveal the dose-dependent laxative effect and potential mechanism of AMR on loperamide-induced slow transit constipation (STC) rats. MATERIALS AND METHODS: Loperamide-induced constipation rat model was established and the dose-dependent laxative effect of AMR was investigated. Untargeted metabolomics based on an UPLC-Q/TOF-MS technique combined with western blot analysis was used to explain the potential mechanism of AMR relieve loperamide-induced constipation in rats. RESULTS: The results showed that medium dose of AMR (AMR-M, 4.32 g raw herb/kg) and high dose of AMR (AMR-H, 8.64 g raw herb/kg) treatments significantly increased the fecal water content, Bristol score, gastrointestinal transit rate, and recovered the damaged colon tissues of constipated rats, but low dose of AMR (AMR-L, 2.16 g raw herb/kg) did not show laxative effect. Both AMR-M and AMR-H treatments also remarkably reduced the serum levels of vasoactive intestinal peptide (VIP), somatostatin (SS) and dopamine (DA), and increased the levels of motilin (MTL), gastrin (GAS) and 5-hydroxytryptamine (5-HT). Urine metabolomics revealed that constipation development was mainly ascribed to the perturbed tryptophan metabolism, and AMR-M and AMR-H markedly corrected the abnormal levels of five urine tryptophan metabolites, namely 4,6-dihydroxyquinoline, indole, 4,8-dihydroxyquinoline, 5-hydroxytryptamine, and kynurenic acid. Additionally, western blot analysis confirmed that the abnormal expression of rate-limiting enzyme involving in tryptophan metabolism, including tryptophan hydroxylase (TPH), monoamine oxidase (MAO) and indoleamine-2,3-dioxygenase (IDO) in the colon of constipated rats, were mediated by AMR-M and AMR-H. CONCLUSIONS: The findings provide insight into the mechanisms of STC and AMR could be developed as new therapeutic agent for prevention or healing of constipation.


Assuntos
Atractylodes , Loperamida , Ratos , Humanos , Animais , Loperamida/uso terapêutico , Laxantes/farmacologia , Atractylodes/química , Triptofano , Rizoma/química , Serotonina , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico
17.
Rev Gastroenterol Mex (Engl Ed) ; 88(4): 404-428, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38097437

RESUMO

Fecal incontinence is the involuntary passage or the incapacity to control the release of fecal matter through the anus. It is a condition that significantly impairs quality of life in those that suffer from it, given that it affects body image, self-esteem, and interferes with everyday activities, in turn, favoring social isolation. There are no guidelines or consensus in Mexico on the topic, and so the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, neurogastroenterologists, and surgeons) to carry out the «Mexican consensus on fecal incontinence¼ and establish useful recommendations for the medical community. The present document presents the formulated recommendations in 35 statements. Fecal incontinence is known to be a frequent entity whose incidence increases as individuals age, but one that is under-recognized. The pathophysiology of incontinence is complex and multifactorial, and in most cases, there is more than one associated risk factor. Even though there is no diagnostic gold standard, the combination of tests that evaluate structure (endoanal ultrasound) and function (anorectal manometry) should be recommended in all cases. Treatment should also be multidisciplinary and general measures and drugs (lidamidine, loperamide) are recommended, as well as non-pharmacologic interventions, such as biofeedback therapy, in selected cases. Likewise, surgical treatment should be offered to selected patients and performed by experts.


Assuntos
Incontinência Fecal , Humanos , Incontinência Fecal/diagnóstico , Incontinência Fecal/terapia , Incontinência Fecal/etiologia , Consenso , México/epidemiologia , Qualidade de Vida , Loperamida/uso terapêutico
18.
Nutrients ; 15(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37960154

RESUMO

Structural changes in the gut microbiota are closely related to the development of functional constipation, and regulating the gut microbiota can improve constipation. Rifaximin is a poorly absorbed antibiotic beneficial for regulating gut microbiota, but few studies have reported its effects on constipation. The purpose of this study was to investigate the effect of rifaximin on loperamide-induced constipation in SD rats. The results showed that rifaximin improved constipation by increasing serum 5-HT, SP, and the mRNA expression of AQP3, AQP8, and reducing the mRNA expression of TLR2 and TLR4. In addition, rifaximin could regulate the gut microbiota of constipated rats, such as increasing the potentially beneficial bacteria Akkermansia muciniphila and Lactobacillus murinus, reducing the Bifidobacterium pseudolongum. According to metabolomics analysis, many serum metabolites, including bile acids and steroids, were changed in constipated rats and were recovered via rifaximin intervention. In conclusion, rifaximin might improve loperamide-induced constipation in rats by increasing serum excitatory neurotransmitters and neuropeptides, modulating water metabolism, and facilitating intestinal inflammation. Muti-Omics analysis results showed that rifaximin has beneficial regulatory effects on the gut microbiota and serum metabolites in constipated rats, which might play critical roles in alleviating constipation. This study suggests that rifaximin might be a potential strategy for treating constipation.


Assuntos
Microbioma Gastrointestinal , Loperamida , Ratos , Animais , Loperamida/efeitos adversos , Rifaximina/efeitos adversos , Ratos Sprague-Dawley , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , RNA Mensageiro
19.
Microbiome ; 11(1): 252, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37951983

RESUMO

BACKGROUND: Perturbations of animal-associated microbiomes from chemical stress can affect host physiology and health. While dysbiosis induced by antibiotic treatments and disease is well known, chemical, nonantibiotic drugs have recently been shown to induce changes in microbiome composition, warranting further exploration. Loperamide is an opioid-receptor agonist widely prescribed for treating acute diarrhea in humans. Loperamide is also used as a tool to study the impact of bowel dysfunction in animal models by inducing constipation, but its effect on host-associated microbiota is poorly characterized. RESULTS: We used conventional and gnotobiotic larval zebrafish models to show that in addition to host-specific effects, loperamide also has anti-bacterial activities that directly induce changes in microbiota diversity. This dysbiosis is due to changes in bacterial colonization, since gnotobiotic zebrafish mono-colonized with bacterial strains sensitive to loperamide are colonized up to 100-fold lower when treated with loperamide. Consistently, the bacterial diversity of gnotobiotic zebrafish colonized by a mix of 5 representative bacterial strains is affected by loperamide treatment. CONCLUSION: Our results demonstrate that loperamide, in addition to host effects, also induces dysbiosis in a vertebrate model, highlighting that established treatments can have underlooked secondary effects on microbiota structure and function. This study further provides insights for future studies exploring how common medications directly induce changes in host-associated microbiota. Video Abstract.


Assuntos
Loperamida , Microbiota , Humanos , Animais , Loperamida/efeitos adversos , Peixe-Zebra/microbiologia , Disbiose/induzido quimicamente , Constipação Intestinal/induzido quimicamente , Bactérias
20.
Cell Mol Biol (Noisy-le-grand) ; 69(10): 23-29, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37953588

RESUMO

Slow transit constipation (STC) is a prevalent chronic colonic dysfunction disease that significantly impairs the quality of life for affected individuals. Yunpi Tongbian Fang (YPTBF), a traditional Chinese medicine compound, has demonstrated promising clinical efficacy; however, its underlying mechanism remains elusive. In order to assess the laxative properties of YPTBF, which encompasses the influence on gut microbiota, gut metabolites, gut neurotransmitters, and colon histology, an oral administration of YPTBF was conducted for a duration of two consecutive weeks on STC rats induced by loperamide hydrochloride. The results showed that YPTBF improved the symptoms of STC, alleviated the decrease in total fecal volume and fecal water content caused by loperamide-induced constipation, restored intestinal transport function, and HE staining showed the recovery of pathological damage to the colon mucosa. In addition, YPTBF increased the concentrations of 5-HT and ACHE, while reducing the concentrations of VIP and NO. YPTBF adjusted the diversity and abundance of gut microbiota in STC rats, enabling the recovery of beneficial bacteria and promoting the production of acetic acid, propionic acid, and butyric acid. We found that YPTBF can improve constipation in STC rats, possibly by regulating the intestinal microbiota structure and improving SCFAs metabolism.


Assuntos
Microbioma Gastrointestinal , Loperamida , Ratos , Animais , Loperamida/efeitos adversos , Qualidade de Vida , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Ácidos Graxos Voláteis/efeitos adversos , Ácido Butírico
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