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Biomedicine & Pharmacotherapy =... May 2023Constipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian Capsule (SHTB) is a traditional Chinese medicine (TCM) which...
Shouhui Tongbian Capsules induce regression of inflammation to improve intestinal barrier in mice with constipation by targeted binding to Prkaa1: With no obvious toxicity.
Constipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian Capsule (SHTB) is a traditional Chinese medicine (TCM) which effectively improve the symptoms of constipation. However, the mechanism has not been fully evaluated. The purpose of this study was to evaluate the effect of SHTB on the symptoms and intestinal barrier of mice with constipation. Our data showed that SHTB effectively improved the constipation induced by diphenoxylate, which was confirmed by shorter first defecation time, higher internal propulsion rate and fecal water content. Additionally, SHTB improved the intestinal barrier function, which was manifested by inhibiting the leakage of Evans blue in intestinal tissues and increasing the expression of occludin and ZO-1. SHTB inhibited NLRP3 inflammasome signaling pathway and TLR4/NF-κB signaling pathway, reduced the number of proinflammatory cell subsets and increased the number of immunosuppressive cell subsets to relieve inflammation. The photochemically induced reaction coupling system combined with cellular thermal shift assay and central carbon metabolomics technology confirmed that SHTB activated AMPKα through targeted binding to Prkaa1 to regulate Glycolysis/Gluconeogenesis and Pentose Phosphate Pathway, and finally inhibited intestinal inflammation. Finally, no obvious toxicity related to SHTB was found in a repeated drug administration toxicity test for consecutive 13 weeks. Collectively, we reported SHTB as a TCM targeting Prkaa1 for anti-inflammation to improve intestinal barrier in mice with constipation. These findings broaden our knowledge of Prkaa1 as a druggable target protein for inflammation inhibition, and open a new avenue to novel therapy strategy for constipation injury.
Topics: Animals; Mice; Constipation; Inflammation; Intestines; NF-kappa B; Signal Transduction; AMP-Activated Protein Kinases
PubMed: 36906969
DOI: 10.1016/j.biopha.2023.114495 -
Indian Journal of Pharmacology May 2011The objective of the study was to investigate the effect of the leaf extract of Rosa canina L. against experimental diarrhea induced by castor oil in rodents.
OBJECTIVES
The objective of the study was to investigate the effect of the leaf extract of Rosa canina L. against experimental diarrhea induced by castor oil in rodents.
MATERIALS AND METHODS
The methanol extract of Rosa canina L. (30 and 60 mg/kg body weight) was administered orally to two groups of mice (five animals per group) in order to evaluate the activity of the extract against the castor oil-induced diarrhea model in mice. Two other groups received normal saline and diphenoxylate (5 mg/kg) as positive control. The effect of the extract on intestinal transit and castor oil-induced intestinal fluid accumulation (enteropooling) was assessed. The effects of the extract on the isolated rabbit jejunum and on the isolated rat ileum were studied.
RESULTS
The preliminary phytochemical screening of the leaf extract of Rosa Canina L. revealed the presence of alkaloids, flavonoids, glycosides, saponins, and volatile oil. Intraperitoneal LD50 of the extract was found to be 455.19 ± 23 mg/kg in mice. The antidiarrheal effect of the methanolic extract exhibited a concentration-dependent inhibition of the spontaneous pendular movement of the isolated rabbit jejunum and inhibited acetylcholine-induced contraction of the rat ileum. A dose-dependent decrease in gastrointestinal transit was observed with extracts (30 and 60 mg/kg), which also protected mice against castor oil-induced diarrhea and castor oil-induced fluid accumulation, respectively.
CONCLUSIONS
The presence of some of the phytochemicals in the leaf extract may be responsible for the observed effects, and also the basis for its use in traditional medicine as an antidiarrheal drug.
PubMed: 21713098
DOI: 10.4103/0253-7613.81510 -
Bioscience Reports May 2019Slow transit constipation (STC) is a common disease characterized by markedly delayed colonic transit time as a result of colonic motility dysfunction. It is well...
Slow transit constipation (STC) is a common disease characterized by markedly delayed colonic transit time as a result of colonic motility dysfunction. It is well established that STC is mostly caused by disorders of relevant nerves, especially the enteric nervous system (ENS). Colonic electrical stimulation (CES) has been regarded as a valuable alternative for the treatment of STC. However, little report focuses on the underlying nervous mechanism to normalize the delayed colonic emptying and relieve symptoms. In the present study, the therapeutic effect and the influence on ENS triggered by CES were investigated in STC beagles. The STC beagle model was established by oral administration of diphenoxylate/atropine and alosetron. Histopathology, electron microscopy, immunohistochemistry, Western blot analysis and immunofluorescence were used to evaluate the influence of pulse train CES on myenteric plexus neurons. After 5 weeks of treatment, CES could enhance the colonic electromyogram (EMG) signal to promote colonic motility, thereby improving the colonic content emptying of STC beagles. HE staining and transmission electron microscopy confirmed that CES could regenerate ganglia and synaptic vesicles in the myenteric plexus. Immunohistochemical staining showed that synaptophysin (SYP), protein gene product 9.5 (PGP9.5), cathepsin D (CAD) and S-100B in the colonic intramuscular layer were up-regulated by CES. Western blot analysis and immunofluorescence further proved that CES induced the protein expression of SYP and PGP9.5. Taken together, pulse train CES could induce the regeneration of myenteric plexus neurons, thereby promoting the colonic motility in STC beagles.
Topics: Animals; Colon; Constipation; Dogs; Electric Stimulation; Female; Myenteric Plexus; Neurons; Regeneration; Synaptophysin
PubMed: 31064818
DOI: 10.1042/BSR20182405 -
Asian Pacific Journal of Tropical... Feb 2012To investigate the antidiarrheal activity of the methanol leaf extract of Pterocarpus erinaceus in vivo.
OBJECTIVE
To investigate the antidiarrheal activity of the methanol leaf extract of Pterocarpus erinaceus in vivo.
METHODS
The methanol leaf extract of Pterocarpus erinaceus was evaluated using different doses (100, 200 and 400 mg/kg body weight) orally for antidiarrheal activity using castor oil-induced diarrhea, charcoal meal transit time and castor oil-induced enteropooling in different groups of albino Wistar mice. The activity of the extract at different doses were compared to diphenoxylate (5 mg/kg) and atropine sulphate (3 mg/kg) which were used as standard reference drugs and also to the distilled water administered negative control group of mice.
RESULTS
The extract at the doses used caused a significant (P< 0.01) reduction in the wet faeces passed by the mice in the castor oil-induced diarrhea, decreased the distance travelled by the charcoal meal by up to 54.8% and also caused a dose dependent and significant (P< 0.001) reduction in the intraluminal fluid accumulation in the castor oil-induced enteropooling.
CONCLUSIONS
Our results indicate that Pterocarpus erinaceus extract produced significant antidiarrheal activity and the action may attribute to inhibition of gastrointestinal movement and fluid secretion.
Topics: Animals; Antidiarrheals; Castor Oil; Diarrhea; Gastrointestinal Motility; Male; Methanol; Mice; Plant Extracts; Plant Leaves; Pterocarpus; Rats, Wistar
PubMed: 22221760
DOI: 10.1016/S1995-7645(12)60014-5 -
Medical Science Monitor : International... Jul 2019BACKGROUND The aim of this study was to evaluate the effects of a new type of dietary fiber - high specific volume polysaccharide (HSVP) - on fecal properties, serum...
BACKGROUND The aim of this study was to evaluate the effects of a new type of dietary fiber - high specific volume polysaccharide (HSVP) - on fecal properties, serum vasoactive intestinal peptide (VIP) concentration, intestinal flora count, and expression of the VIP-cAMP-PKA-AQP3 signaling pathway. MATERIAL AND METHODS Compound diphenoxylate was used in 48 healthy Wistar rats to establish a constipation model. Rats were divided into a normal control group, a constipation model group, an HSVP low-dose group, an HSVP medium-dose group, an HSVP high-dose group, and a fructose control group. We used colony count method, ELISA, WB, and RT-PCR to determine fecal moisture content, fecal hardness, fecal passage time, serum VIP concentration, number of intestinal bacteria, and VIP-cAMP-PKA-AQP3 signal pathway protein expression. RESULTS The constipation model was established successfully. HSVP (the medium dose was 10% and the high dose was 15%) improved fecal moisture content, reduced hardness, shortened fecal emptying time, increased intestinal bacteria, reduced serum VIP concentration, downregulated cAMP and PKAm RNA transcription, reduced protein expression, and reduced intestinal AQP3 expression. CONCLUSIONS HSVP improved constipation, increased the number of intestinal bacteria, and elevated expression of the VIP-cAMP-PKA-AQP3 signaling pathway. The mechanism of HSVP in regulating intestinal water metabolism in constipated rats may occur through the VIP-cAMP-PKA-AQP3 signaling pathway, and be closely related to changes in intestinal bacteria. The important role of the brain-gut-microbiome axis in the pathogenesis of constipation has been confirmed in this study.
Topics: Animals; Aquaporin 3; Constipation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dietary Fiber; Feces; Gastrointestinal Microbiome; Gastrointestinal Transit; Hardness; Humidity; Intestines; Polysaccharides; RNA, Messenger; Rats, Wistar; Transcription, Genetic; Treatment Outcome; Vasoactive Intestinal Peptide; Water
PubMed: 31280283
DOI: 10.12659/MSM.916526 -
Hong Kong Medical Journal = Xianggang... Dec 2005We report two cases of unintentional poisoning with anticholinergic agents. The first patient, a 7-year-old girl, was prescribed four different medications by a general...
We report two cases of unintentional poisoning with anticholinergic agents. The first patient, a 7-year-old girl, was prescribed four different medications by a general practitioner for treatment of abdominal colic and diarrhoea. All drugs had anticholinergic properties. The second patient, a 16-month-old boy, ingested his mother's cyproheptadine tablets. Both children presented with central and peripheral symptoms and signs compatible with acute anticholinergic syndrome. They recovered spontaneously following intravenous fluid replacement and close observation. Gastric lavage was also performed on the boy. Poisoning with cholinergic antagonists in children is a potentially serious hazard in Hong Kong. It may be avoided by careful prescribing on the part of general practitioners and safe storage of all medicinal products in the home environment.
Topics: Antidiarrheals; Atropine; Child; Cholinergic Antagonists; Colic; Cyproheptadine; Diphenoxylate; Drug Combinations; Drug Overdose; Drug Therapy, Combination; Female; Gastric Lavage; Hong Kong; Humans; Infant; Male; Medication Errors; Radiography
PubMed: 16340032
DOI: No ID Found -
BMC Complementary and Alternative... Mar 2012Constipation is a very common health problem in the world. Intake of sufficient amount of dietary fibers is a cornerstone in the prevention and treatment of...
BACKGROUND
Constipation is a very common health problem in the world. Intake of sufficient amount of dietary fibers is a cornerstone in the prevention and treatment of constipation. As a traditional medicine, flaxseed has been used to treat constipation for centuries, but the controlled trials are rare. The purpose of the present study was to assess that whether partially defatted flaxseed meal (PDFM) has the potential role to facilitate fecal output in normal and experimental constipated mice.
METHODS
After supplemented with 2.5%, 5% and 10% (w/w) PDFM (L-, M- and H-PDFM) for 14 days, the constipation models of mice were induced by atropine-diphenoxylate. The small intestinal transit rates, start time of defecation, amount of defecation and wet weight of feces were researched in normal and constipation model mice.
RESULTS
M- and H-PDFM significantly increase small intestinal transit rates in constipation model mice. All dose of PDFM markedly shortened the start time of defecation and M- and H-PDFM significantly increase stool frequency and weight in both normal and constipation model mice.
CONCLUSIONS
PDFM may be a useful laxative to facilitate fecal output in normal and constipation conditions.
Topics: Animals; Constipation; Defecation; Dietary Fiber; Dietary Supplements; Disease Models, Animal; Feces; Flax; Gastrointestinal Transit; Intestine, Small; Laxatives; Male; Mice; Mice, Inbred Strains; Phytotherapy; Plant Preparations; Seeds
PubMed: 22400899
DOI: 10.1186/1472-6882-12-14 -
British Medical Journal Jun 1980In the 20 years 1958-77 598 deaths were registered as due to accidental poisoning in British children under the age of 10-343 boys and 255 girls. Drugs caused 484...
In the 20 years 1958-77 598 deaths were registered as due to accidental poisoning in British children under the age of 10-343 boys and 255 girls. Drugs caused 484 deaths, non-medicinal products 111, and plants three. The annual number of deaths reached a peak in 1964 but fell steadily thereafter; 16 deaths occurred in 1977. After 1970 tricyclic antidepressants replaced salicylates as the most commonly fatal poison. The next ten drugs most often recorded in 1970-7 were, in order, opiates (including diphenoxylate/atropine (Lomotil)), barbiturates, digoxin, orphenadrine (Disipal), quinine, potassium, iron, fenfluramine (Ponderax), antihistamines, and phenothiazines. In 20 years paracetamol caused one death, and before 1976 deaths caused by aspirin had fallen to fewer than two a year. Thus the introduction in 1976 and 1977 of safety packaging of these drugs can be expected to have little impact on the mortality from them in childhood.
Topics: Accidents, Home; Child; Child, Preschool; Female; Humans; Iatrogenic Disease; Infant; Infant, Newborn; Male; Plant Poisoning; Poisoning; Salicylates; United Kingdom
PubMed: 7427181
DOI: 10.1136/bmj.280.6231.1595 -
Cancer Management and Research 2016Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%-7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity...
Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%-7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg/d ceritinib dose.
PubMed: 27069372
DOI: 10.2147/CMAR.S96471 -
The Kaohsiung Journal of Medical... Jun 2024Slow transit constipation (STC) is one of the most common gastrointestinal disorders in children and adults worldwide. Paeoniflorin (PF), a monoterpene glycoside...
Slow transit constipation (STC) is one of the most common gastrointestinal disorders in children and adults worldwide. Paeoniflorin (PF), a monoterpene glycoside compound extracted from the dried root of Paeonia lactiflora, has been found to alleviate STC, but the mechanisms of its effect remain unclear. The present study aimed to investigate the effects and mechanisms of PF on intestinal fluid metabolism and visceral sensitization in rats with compound diphenoxylate-induced STC. Based on the evaluation of the laxative effect, the abdominal withdrawal reflex test, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry were used to detect the visceral sensitivity, fluid metabolism-related proteins, and acid-sensitive ion channel 3/extracellular signal-regulated kinase (ASIC3/ERK) pathway-related molecules. PF treatment not only attenuated compound diphenoxylate-induced constipation symptoms and colonic pathological damage in rats but also ameliorated colonic fluid metabolic disorders and visceral sensitization abnormalities, as manifested by increased colonic goblet cell counts and mucin2 protein expression, decreased aquaporin3 protein expression, improved abdominal withdrawal reflex scores, reduced visceral pain threshold, upregulated serum 5-hydroxytryptamine, and downregulated vasoactive intestinal peptide levels. Furthermore, PF activated the colonic ASIC3/ERK pathway in STC rats, and ASIC3 inhibition partially counteracted PF's modulatory effects on intestinal fluid and visceral sensation. In conclusion, PF alleviated impaired intestinal fluid metabolism and abnormal visceral sensitization in STC rats and thus relieved their symptoms through activation of the ASIC3/ERK pathway.
Topics: Animals; Glucosides; Monoterpenes; Acid Sensing Ion Channels; Constipation; Rats; Male; MAP Kinase Signaling System; Rats, Sprague-Dawley; Colon; Gastrointestinal Transit; Aquaporin 3; Serotonin; Visceral Pain
PubMed: 38634140
DOI: 10.1002/kjm2.12829