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Fortunato-Silva J, de Rezende LP, Ferreira-Neto ML, Bispo-da-Silva LB, Balbi APC. Intrauterine exposure to a high-fat diet, with different levels of lipids, and its gastrointestinal repercussions: a model of fetal programming in rats. J Dev Orig Health Dis 2024; 15:e33. [PMID: 39711030 DOI: 10.1017/s2040174424000382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2024]
Abstract
It is known that adverse stimuli, such as altered diets during pregnancy and lactation, can result in deleterious effects on the progeny. The aim of this study was to evaluate the possible gastrointestinal repercussions in the offspring of Wistar rats exposed to high-fat diets. Pregnant rats were divided into three groups: normolipidic diet (3.5% lipids), a diet containing 28% lipids, and a diet with 40% lipids. Body weight and food, water, daily caloric, and macronutrient intake were evaluated in the pregnant rats. Structural and functional gastrointestinal parameters were assessed in 30-day-old male pups. Depending on the lipid content of the maternal diet, the pups may exhibit gastric mucosal thickening, an increase in the relative weight of the small intestine, a reduction in the jejunal and ileal mucosa, and a decrease in the total thickness of the ileum. Additionally, there may be a reduction in the number of villi per area in these organs and a thinning of the muscular layer in the large intestine. The structural changes induced by the maternal high-fat diet seem to reduce the stomach's sensitivity to ethanol-induced ulcers, which is the only functional alteration observed. Therefore, the offspring of dams exposed to high-fat diets during pregnancy and lactation exhibits impaired gastrointestinal development, with alterations depending on dietary fat content and specific gastrointestinal regions. Structural changes did not always result in functional abnormalities and, in some cases, appeared protective. The long-term consequences of the observed morphological alterations require further investigation.
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Affiliation(s)
- Jéssica Fortunato-Silva
- Program in Applied Structural and Cellular Biology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil
| | - Lívia Prometti de Rezende
- Program in Applied Structural and Cellular Biology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil
| | - Marcos Luiz Ferreira-Neto
- Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil
| | - Luiz Borges Bispo-da-Silva
- Department of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil
| | - Ana Paula Coelho Balbi
- Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Brazil
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Brinsi C, Jedidi S, Sammari H, Selmi H, Sebai H. Antidiarrheal, anti-inflammatory and antioxidant effects of Anethum graveolens L. fruit extract on castor oil-induced diarrhea in rats. Neurogastroenterol Motil 2024; 36:e14892. [PMID: 39115258 DOI: 10.1111/nmo.14892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 07/04/2024] [Accepted: 07/29/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND Between food and medicine, nutraceuticals are widely used in human health for the prevention and treatment of various diseases. This study aims to determine the cytoprotective effects of Anethum gravelons fruit extract (AGFAE) on castor oil-induced diarrhea in rats due to its phytochemical and antioxidant properties. METHODS Male rats were divided into six groups of six animals each: Control (C), Castor oil (CO), CO + different doses of AGFAE (50, 100, and 200 mg/kg, b.w., p.o.), and the CO + loperamide group (LOP, 10 mg/kg, b.w., p.o.). KEY RESULTS In vitro, the chemical composition of aqueous Dill fruit extract showed strong antioxidant activity, with a high content of total polyphenols, flavonoids, and tannins. In our in vivo studies, pre-treatment with AGFAE reduced malondialdehyde and hydrogen peroxide levels and maintained normal activity of enzymatic and non-enzymatic antioxidants in the gastric and intestinal mucosa. In addition, we found that AGFAE prophylaxis improved the stability of many plasma biochemical parameters altered by castor oil intoxication, such as C-reactive protein concentrations and alkaline phosphatase activities. CONCLUSIONS & INFERENCES We suggest that AGFAE phenolic compounds had significant protection against diarrhea involving several mechanisms such as reducing hypersecretion, peristaltic, inflammation, and preserving the endogenous antioxidant levels.
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Affiliation(s)
- Chirine Brinsi
- Laboratory of Functional Physiology and Valorization of Bio-Resources (LR23ES08), University of Jendouba, Higher Institute of Biotechnology of Béja, Béja, Tunisia
| | - Saber Jedidi
- Laboratory of Functional Physiology and Valorization of Bio-Resources (LR23ES08), University of Jendouba, Higher Institute of Biotechnology of Béja, Béja, Tunisia
- Laboratory of Sylvo-Pastoral Resources, Institution of Agricultural Research and Higher Education (IRESA), University of Jendouba, Sylvo- Pastoral Institute of Tabarka, Tabarka, Tunisia
| | - Houcem Sammari
- Laboratory of Functional Physiology and Valorization of Bio-Resources (LR23ES08), University of Jendouba, Higher Institute of Biotechnology of Béja, Béja, Tunisia
| | - Houcine Selmi
- Laboratory of Sylvo-Pastoral Resources, Institution of Agricultural Research and Higher Education (IRESA), University of Jendouba, Sylvo- Pastoral Institute of Tabarka, Tabarka, Tunisia
| | - Hichem Sebai
- Laboratory of Functional Physiology and Valorization of Bio-Resources (LR23ES08), University of Jendouba, Higher Institute of Biotechnology of Béja, Béja, Tunisia
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Ma YL, Wu ZM, Liu X, Lan JE, Zai WJ, Jin X, Xie H, Mu Q, Liu HR. Antidiarrheal activity of the extracts of Valeriana jatamansi Jones on castor oil-induced diarrhea mouse by regulating multiple signal pathways. JOURNAL OF ETHNOPHARMACOLOGY 2022; 298:115560. [PMID: 35863616 DOI: 10.1016/j.jep.2022.115560] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 07/10/2022] [Accepted: 07/13/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Valeriana jatamansi Jones, a traditional medicine, is used for various medicinal purposes worldwide. This species is popular for its gastro-protective properties and has been verified to exert antidiarrheal effects. Qiuxieling mixture, an oral liquid preparation used to treat diarrhea in children in clinical practice, was extracted from V. jatamansi Jones. AIM OF THE STUDY Although Qiuxieling mixture has a good preventive effect on diarrhea children, the disgusting smell makes it intolerable. Therefore, we extracted odorless products from V. jatamansi Jones and Qiuxieling mixture. The present study is aimed to investigate the protective effects of two ethanolic extracts of V. jatamansi Jones and Qiuxieling mixture against castor oil-induced diarrhea and their possible mechanisms in mice. MATERIALS AND METHODS The two extracts of V. jatamansi Jones and Qiuxieling mixture were detected by HPLC. A castor oil-induced diarrheal model was used to evaluate the antidiarrheal effects. The expression of Occludin in the small intestine was measured by IHC. Western blotting and immunofluorescence were used to detect the expression of proteins related to the oxidative stress and GSDMD-mediated pyroptosis signaling pathways. ELISA was used to detect the expression of IL-6 and IL-1β in the small intestine of mice with diarrhea. RESULTS The two extracts of V. jatamansi Jones and Qiuxieling mixture dose-dependently reduced the diarrhea index and the diarrhea rate, delayed the onset of diarrhea, and decreased the weight of the intestinal content. Meanwhile, they reversed the decreased expression of Occludin and restored the activity of Na+-K+-ATPase in the intestines of diarrheal mice. In addition, they reversed the depletion of GSH, attenuated the activation of the ERK/JNK pathway, promoted the Nrf2/SOD1 signaling pathways, and decreased the release of ROS in the intestines of diarrheal mice. Moreover, they suppressed GSDMD-mediated pyroptosis by downregulating the NLRP3/caspase-1/GSDMD signaling pathway. CONCLUSIONS The two extracts of V. jatamansi Jones and Qiuxieling mixture exerted protective effects on castor oil-induced diarrhea in mice through a variety of mechanisms, including antioxidant stress, restoration of tight junctions between intestinal mucosal cells and regulation of the GSDMD-mediated pyroptosis pathway.
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Affiliation(s)
- Yu-Lei Ma
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, PR China
| | - Zi-Mei Wu
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, PR China; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, PR China
| | - Xiao Liu
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, PR China
| | - Jiang-Er Lan
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, PR China
| | - Wen-Jing Zai
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, PR China
| | - Xin Jin
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, PR China
| | - Hui Xie
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, PR China
| | - Qing Mu
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, PR China.
| | - Hong-Rui Liu
- Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, 201203, PR China.
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Pharmacological Potential of Avicennia alba Leaf Extract: An Experimental Analysis Focusing on Antidiabetic, Anti-inflammatory, Analgesic, and Antidiarrheal Activity. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7624189. [PMID: 35572728 PMCID: PMC9106461 DOI: 10.1155/2022/7624189] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 04/21/2022] [Indexed: 02/07/2023]
Abstract
Avicennia alba is a mangrove plant that is extensively used to treat severe health issues. This focus of this study was to investigate the antidiabetic, anti-inflammatory, analgesic, and antidiarrheal activities of methanolic extract of A. alba leaves in Swiss albino mouse model. The antidiabetic, anti-inflammatory, analgesic, and antidiarrheal activities of the leaf extract were performed using alloxan-monohydrate, carrageenan-induced paw edema, acetic acid-induced writhing test and the hot plate method, and castor oil-induced method, respectively. The extract was used at doses ranging from 200 to 500 mg/kg to conduct the investigation. Leaf extract at 400 and 500 mg/kg showed potent antidiabetic activity in alloxan-induced diabetic mice. Advanced research is needed to control blood glucose levels and carrageenan paw edema-based anti-inflammatory effects. Both tests showed statistically significant result in a dose-dependent manner. The maximum dose (500 mg/kg) demonstrated potent analgesic activity in both writhing test and hot plate method. The plant extract also showed significant antidiarrheal activity at 400 and 500 mg/kg in experimental mice. However, more research is needed to explore the possible mechanisms and isolate the compounds associated with these bioactivities from the leaf extract of A. alba.
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Ateba SB, Njamen D, Krenn L. The Genus Eriosema (Fabaceae): From the Ethnopharmacology to an Evidence-Based Phytotherapeutic Perspective? Front Pharmacol 2021; 12:641225. [PMID: 34025412 PMCID: PMC8138667 DOI: 10.3389/fphar.2021.641225] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Accepted: 02/17/2021] [Indexed: 01/13/2023] Open
Abstract
The genus Eriosema (Fabaceae) includes approximately 150 species widely distributed across tropical and subtropical regions of the world (Africa, Neotropics, Asia and Australia). Throughout these regions, several species are used since centuries in different traditional medicinal systems, while others are used as food or food supplement. The present review attempts to critically summarize current information concerning the uses, phytochemistry and pharmacology of the Eriosema genus and to evaluate the therapeutic potential. The information published in English and French (up to September 2020) on ethnopharmacology or traditional uses, chemistry, pharmacology and toxicology of Eriosema genus was collected from electronic databases [SciFinder, PubMed, Google, Google Scholar, Scopus, Web of Science, Prelude Medicinal Plants—http://www.ethnopharmacologia.org/recherche-dans-prelude/?plant, The Plant List (http://www.theplantlist.org/), POWO (http://powo.science.kew.org/) and IUCN Red List Categories (https://www.iucnredlist.org/)], conference proceedings, books, M.Sc. and Ph.D. dissertations. The information retrieved on the ethnomedicinal indications of Eriosema genus allowed to list 25 species (∼16.6% of the genus). The majority of uses is recorded from Africa. Phytochemical analyses of 8 species led to the identification and/or isolation of 107 compounds, with flavonoids (69.2%), chromones (7.5%) and benzoic acid derivatives (3.7%) as the main chemical classes. Pharmacological investigations with crude extracts and isolated compounds showed a broad range of activities including aphrodisiac, estrogenic, anti-osteoporosis, hypolipidemic, anti-diabetic, anti-diarrheal, anti-microbial, anti-oxidant, anthelmintic, anti-cancer, and acetylcholinesterase inhibitory activities. Despite the low number of Eriosema species tested, there is convincing evidence in vitro and in vivo studies validating some traditional and ethnobotanical uses. However, the utility of several of the described uses has not yet been confirmed in pharmacological studies. Reviewed data could serve as a reference tool and preliminary information for advanced research on Eriosema species.
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Affiliation(s)
- Sylvin Benjamin Ateba
- Department of Biology of Animal Organisms, Faculty of Science, University of Douala, Douala, Cameroon
| | - Dieudonné Njamen
- Laboratory of Animal Physiology, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon
| | - Liselotte Krenn
- Department of Pharmacognosy, University of Vienna, Vienna, Austria
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Zewdie KA, Bhoumik D, Wondafrash DZ, Tuem KB. Evaluation of in-vivo antidiarrhoeal and in-vitro antibacterial activities of the root extract of Brucea antidysenterica J. F. Mill (Simaroubaceae). BMC Complement Med Ther 2020; 20:201. [PMID: 32605618 PMCID: PMC7325256 DOI: 10.1186/s12906-020-03001-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 06/25/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Diarrhoea has been the major cause of death especially in children of developing countries. Brucea antidysenterica is one of the several medicinal plants used traditionally for the treatment of diarrhoea in Ethiopia. Hence, the present study was undertaken to investigate the antidiarrhoeal and antibacterial activities of the root extract of B. antidysenterica. METHODS Plant material was extracted by maceration technique using 80% methanol. The antidiarrhoeal activity was tested using castor oil-induced diarrhoea, castor oil-induced charcoal meal test, and castor oil-induced enteropooling models in mice. Whilst, the antibacterial activity of the crude extract was evaluated using agar well diffusion and broth microdilution methods. RESULTS The 80% methanolic crude extract significantly delayed the diarrhoeal onset at the two higher doses (p < 0.001) and it has also inhibited the number and weight of faecal output at all tested doses as compared with the negative control. Moreover, it showed a significant anti-motility effect (p < 0.001) at all tested doses. Whereas it displayed a significant reduction in the weight and volume of intestinal contents at the doses of 200 and 400 mg/kg (p < 0.01). The highest concentration (800 mg/mL) of test extract showed maximum zone of inhibition in all tested standard strains of bacteria (18.3 mm-22 mm). While MIC and MBC values (0.39 mg/mL and 1.56 mg/mL) showed that S. flexneri was the most susceptible pathogen for test extract. CONCLUSION The study revealed that the root extract of B. antidysenterica has antidiarrhoeal and antibacterial activities.
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Affiliation(s)
- Kaleab Alemayehu Zewdie
- Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, 1871, Mekelle, Ethiopia.
| | - Dayananda Bhoumik
- Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, 1871, Mekelle, Ethiopia
| | - Dawit Zewdu Wondafrash
- Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, 1871, Mekelle, Ethiopia
| | - Kald Beshir Tuem
- Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, 1871, Mekelle, Ethiopia
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Unveiling Pharmacological Responses and Potential Targets Insights of Identified Bioactive Constituents of Cuscuta reflexa Roxb. Leaves through In Vivo and In Silico Approaches. Pharmaceuticals (Basel) 2020; 13:ph13030050. [PMID: 32245131 PMCID: PMC7151675 DOI: 10.3390/ph13030050] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 03/18/2020] [Accepted: 03/19/2020] [Indexed: 01/02/2023] Open
Abstract
Cuscuta reflexa Roxb. is traditionally used by the indigenous communities of Bangladesh to treat different diseases, such as pain, edema, tumor, jaundice, and skin infections. This study tested neuro-pharmacological, anti-nociceptive, and antidiarrheal activities by in vivo and in silico experiments for the metabolites extracted (methanol) from the leaves of Cuscuta reflexa (MECR). During the anxiolytic evaluation analyzed by elevated plus maze and hole board tests, MECR (200 and 400 mg/kg) exhibited a significant dose-dependent reduction of anxiety-like behavior in mice. Similarly, mice treated with MECR demonstrated a dose-dependent decrease in the time of immobility in both forced swimming and tail suspension tests. In addition, anti-nociceptive activity was assessed by the chemical-induced (acetic acid and formalin) pain models. In both cases, 400 mg/kg was found to be most effective and significantly (p < 0.001) inhibited acetic acid stimulated writhing and formalin-induced licking (pain response) in mice. Furthermore, antidiarrheal efficacy determined by the castor-oil induced diarrheal model manifested an evident inhibition of diarrheal stool frequency. In parallel, previously isolated bioactive compounds were documented based on the biological activities and subjected to in silico studies to correlate with the current pharmacological outcomes. The selected isolated compounds (15) displayed favorable binding affinities to potassium channels, human serotonin receptor, COX-1, COX-2, M3 muscarinic acetylcholine receptor, and 5-HT3 receptor proteins. Additionally, the ADME/T and toxicological properties were justified to unveil their drug-like properties and toxicity level. Overall, Cuscuta reflexa is bioactive and could be a potential source for the development of alternative medicine.
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Methanol soluble fraction of fruits of Annona muricata possesses significant antidiarrheal activities. Heliyon 2020; 6:e03112. [PMID: 31909276 PMCID: PMC6940681 DOI: 10.1016/j.heliyon.2019.e03112] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 07/05/2019] [Accepted: 10/31/2019] [Indexed: 11/21/2022] Open
Abstract
Medicinal plants are the major sources of traditional treatment of disease in Indian subcontinent due to abundant presence of plants and vast side effects of synthetic drug. The present study was subjected to observe in vitro thrombolytic, antibacterial, and in vivo antidiarrheal activities of methanol soluble fraction of fruits of Annona muricata. In thrombolytic activity assay, various concentrations (2 ─ 10 mg/ml) of methanol soluble fraction was used and dose dependently less potent activity was found. The maximum clot lysis 18.33% (p* < 0.05) was achieved at 10 mg/ml of methanolic fruit extract, whereas standard drug streptokinase showed 55.50% (p*** < 0.001) clot lysis. In antibacterial assay, disc diffusion method was used comprising two gram positive (S. aureus and Micrococcus luteus) and two gram negative (E. coli and P. aeruginosa) bacteria. None of four (0.25, 0.5, 1, and 5 mg/disc) concentration of fruit extract showed antibacterial potentiality, whereas standard amikacin (3 mg/disc) revealed strong antibacterial activities (=~ 23 ─ 24 mm of MIC). To evaluate antidiarrheal activity, castor oil induced diarrhea was created in Swiss albino mice and different doses (100, 200, and 400 mg/kgbw) of fruit extract was introduced post orally. All of three different doses of fruit extract showed significant (p < 0.05 ─ 0.001) antidiarrheal activities. Notably, the percent inhibition of diarrhea by methanolic extract of fruits of Annona muricata was found to be 58.38% at a dose of 400 mg/kgbw. The effect of vehicle saline (10 ml/kgbw) was considered as control and loperamide (5 mg/kgbw) as standard that provided 67.01% inhibition of diarrhea. The results suggest that, the fruits of Annona muricata possess potent antidiarrheal properties, providing scientific basis of using the plant parts in the treatment of diarrheal disease.
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Investigation of the Biological Activities and Characterization of Bioactive Constituents of Ophiorrhiza rugosa var. prostrata (D.Don) & Mondal Leaves through In Vivo, In Vitro, and In Silico Approaches. Molecules 2019; 24:molecules24071367. [PMID: 30965575 PMCID: PMC6480688 DOI: 10.3390/molecules24071367] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 03/29/2019] [Accepted: 04/04/2019] [Indexed: 11/17/2022] Open
Abstract
Ophiorrhiza rugosa var. prostrata is one of the most frequently used ethnomedicinal plants by the indigenous communities of Bangladesh. This study was designed to investigate the antidiarrheal, anti-inflammatory, anthelmintic and antibacterial activities of the ethanol extract of O. rugosa leaves (EEOR). The leaves were extracted with ethanol and subjected to in vivo antidiarrheal screening using the castor oil-induced diarrhea, enteropooling, and gastrointestinal transit models. Anti-inflammatory efficacy was evaluated using the histamine-induced paw edema test. In parallel, in vitro anthelmintic and antibacterial activities were evaluated using the aquatic worm and disc diffusion assays respectively. In all three diarrheal models, EEOR (100, 200 and 400 mg/kg) showed obvious inhibition of diarrheal stool frequency, reduction of the volume and weight of the intestinal contents, and significant inhibition of intestinal motility. Also, EEOR manifested dose-dependent anti-inflammatory activity. Anthelmintic action was deemed significant (P < 0.001) with respect to the onset of paralysis and helminth death. EEOR also resulted in strong zones of inhibition when tested against both Gram-positive and Gram-negative bacteria. GC-MS analysis identified 30 compounds within EEOR, and of these, 13 compounds documented as bioactive showed good binding affinities to M3 muscarinic acetylcholine, 5-HT3, tubulin and GlcN-6-P synthase protein targets in molecular docking experiments. Additionally, ADME/T and PASS analyses revealed their drug-likeness, likely safety upon consumption and possible pharmacological activities. In conclusion, our findings scientifically support the ethnomedicinal use and value of this plant, which may provide a potential source for future development of medicines.
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Ferraz CR, Silva DB, Prado LCDS, Canabrava HAN, Bispo-da-Silva LB. Antidiarrhoeic effect and dereplication of the aqueous extract of Annona crassiflora (Annonaceae). Nat Prod Res 2017; 33:563-567. [DOI: 10.1080/14786419.2017.1396589] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Camila Rodrigues Ferraz
- Department of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia, Minas Gerais, Brazil
| | - Denise Brentan Silva
- Faculty of Pharmaceutical Science at Ribeirão Preto, Núcleo de Pesquisas em Produtos Naturais e Sintéticos (NPPNS), University of São Paulo (FCFRP-USP), São Paulo, Brazil
- Laboratório de Produtos Naturais e Espectrometria de Massas (LAPNEM), Federal University of Mato Grosso do Sul (UFMS), Mato Grosso do Sul, Brazil
| | - Ligia Carolina da Silva Prado
- Department of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia, Minas Gerais, Brazil
| | | | - Luiz Borges Bispo-da-Silva
- Department of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia, Minas Gerais, Brazil
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Formiga RDO, Quirino ZGM, Diniz MDFFM, Marinho AF, Tavares JF, Batista LM. Maytenus erythroxylon Reissek (Celastraceae) ethanol extract presents antidiarrheal activity via antimotility and antisecretory mechanisms. World J Gastroenterol 2017; 23:4381-4389. [PMID: 28706420 PMCID: PMC5487501 DOI: 10.3748/wjg.v23.i24.4381] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 02/24/2017] [Accepted: 03/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the acute toxicity, phytochemical profile, antidiarrheal activity and mechanisms of action of Maytenus erythroxylon (M. erythroxylon) ethanol extract.
METHODS A castor oil-induced diarrhea model was used to evaluate antidiarrheal activity. Intestinal transit and gastric emptying protocols were used to evaluate a possible antimotility effect. KATP channels, nitric oxide, presynaptic α2-adrenergic and tissue adrenergic receptors were investigated to uncover antimotility mechanisms of action and castor oil-induced enteropooling to elucidate antisecretory mechanisms.
RESULTS All tested doses of the extract (62.5, 125, 250 and 500 mg/kg) possessed antidiarrheal activity, with a significant decrease of the evacuation index. This activity is possibly related to a reduced gastric emptying (125, 250 and 500 mg/kg) and to a decreased percentage of intestinal transit for all tested doses. That last effect seems to be modulated by nitric oxide, KATP channels and tissue adrenergic receptors. Besides, the extract also presented antisecretory effect due to a decrease of intestinal fluid accumulation.
CONCLUSION The antidiarrheal effect of M. erythroxylon found in this study involves antimotility and antisecretory mechanisms that may be attributed to the chemical compounds found in this species: saponins, flavonoids, tannins, triterpenes and steroids.
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Tadesse E, Engidawork E, Nedi T, Mengistu G. Evaluation of the anti-diarrheal activity of the aqueous stem extract of Lantana camara Linn (Verbenaceae) in mice. Altern Ther Health Med 2017; 17:190. [PMID: 28376868 PMCID: PMC5379525 DOI: 10.1186/s12906-017-1696-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 03/17/2017] [Indexed: 11/20/2022]
Abstract
Background Diarrheal disease remains a public health problem in developing countries, including Ethiopia. In order to alleviate this disease, Ethiopian traditional healers use a wide range of medicinal plants from which Lantana camara is one of them. The stem of this plant is traditionally used for the treatment of diarrhoea. In addition, this plant is scientifically evaluated to have an antispasmodic effect on in vitro study. The aim of this study was to evaluate the antidiarrheal activity of the aqueous stem extract of L. camara Linn in mice. Methods The antidiarrheal activity of the extract was investigated using castor oil induced diarrhoea, enteropooling and small intestine transit models. The test groups received various doses (100, 200, and 400 mg/kg) of the extract, whereas positive controls received Loperamide (3 mg/kg) and negative controls received distilled water (10 ml/kg). Results In castor oil induced diarrhoea model, the extract, at all test doses, significantly (p < 0.001) prolonged diarrhoea onset, decreased the frequency of defecation, and weight of faeces. Similarly, the extract produced a significant (p < 0.001) decline in the weight and volume of intestinal contents at all tested doses. In addition, a significant (P < 0.001) reduction in the gastrointestinal motility in charcoal meal test was also observed in all doses of the extract. Phytochemical screening of the extract revealed the presence of flavonoids, alkaloids, tannins, and phytosterols that may play a key role in its antidiarrheal activity. Conclusion The obtained results of the present study confirm antidiarrheal activity of the stem of L. camara, thus provide the scientific basis for the traditional uses of this plant as a treatment for diarrhoea.
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Bello FH, Maiha BB, Anuka JA. The effect of methanol rhizome extract of Nymphaea lotus Linn. (Nymphaeaceae) in animal models of diarrhoea. JOURNAL OF ETHNOPHARMACOLOGY 2016; 190:13-21. [PMID: 27215682 DOI: 10.1016/j.jep.2016.05.036] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2015] [Revised: 02/22/2016] [Accepted: 05/16/2016] [Indexed: 05/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Nymphaea lotus, which is widely distributed throughout tropical Africa, enjoys a number of ethnomedical uses in Nigeria. Traditionally, the rhizomes of N. lotus are used to cure diarrhoea. AIM OF STUDY This study aims to evaluate the antidiarrhoeal activity of the methanol rhizome extract of N. lotus plant in laboratory animals. MATERIALS AND METHODS The extract was screened for activity against castor oil-induced diarrhoea and magnesium sulphate-induced diarrhoea as well as effect on gastric transit time in mice. The effect of methanol rhizome extract of Nymphaea lotus on the perfused isolated tissue preparation was also determined. RESULTS For castor oil-induced diarrhoea, the extract at doses of 200, 400 and 800mg/kg produced significant reduction in the frequency of diarrhoea (at p<0.001, p<0.001 and p<0.01 respectively). The extract at 800mg/kg produced a significant delay in onset of diarrhoea (p<0.05) comparable to loperamide (3mg/kg). The frequency of magnesium sulphate-induced diarrhoea was also significantly reduced in the groups treated with 200, 400 and 800mg/kg of the extract at p<0.001, p<0.001 and p<0.01 respectively. At doses of 200mg/kg and 400mg/kg, the protection produced was comparable to loperamide, 3mg/kg. All treated groups produced significant reduction in the transit of charcoal meal along the intestinal tract at p<0.001. The extract at low concentration (4×10(-4)-6.4×10(-2)mg/ml) had contractile effect on the tone of contraction of the rabbit jejunum while at higher concentrations (8×10(-2)-512×10(-2)mg/ml) produced significant reduction in the tone and rate of spontaneous contraction of rabbit jejunum. The extract at lower concentrations (4×10(-4)-2×10(-2)mg/ml) has no effect on contraction of the guinea pig ileum while higher concentrations (4×10(-2)-512×10(-2)mg/ml) produced significant relaxant activity on guinea pig ileum. CONCLUSION This study has shown that the methanol rhizome extract of N. lotus has antidiarrhoeal properties thus justifying its use by the local population for this purpose.
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Affiliation(s)
- Fatima Hauwa Bello
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria.
| | - Bilkisu B Maiha
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
| | - Joseph A Anuka
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria
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Sadraei H, Asghari G, Shahverdi F. Antidiarrhoeal assessment of hydroalcoholic and hexane extracts of Dracocephalum kotschyi Boiss. and apigenin in mice. Res Pharm Sci 2016; 11:200-9. [PMID: 27499789 PMCID: PMC4962300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Dracocephalum kotschyi Boiss, a member of Labiatae family, is a native plant to Iran, which has been reported to have immunomodulatory, antihyperlipidemic and antispasmodic activities. The objective of this research was to study the antispasmodic and antidiarrhoeal activities of hydroalcoholic and hexane extracts of D. kotschyi in mice. Furthermore, the antidiarrhoeal and antispasmodic effect of apigenin, a flavonoid constituent of D. kotschyi, was also studied. Hydroalcoholic and hexane extracts were obtained from aerial part of D. kotschyi using percolation method. Antispasmodic effect of the test compounds was assessed by measurement of small intestine transit following oral administration of a charcoal meal. Diarrhoea was induced by administration of either castor oil (0.5 ml) or magnesium sulphate (MgSO4) (10% w/v solution). Both the hydroalcoholic and hexane extracts of D. kotschyi (10 and 20 mg/kg) reduced the intestinal charcoal meal transit. Loperamide (2 mg/kg) and apigenin (2 and 10 mg/kg) inhibited intestinal movement of the charcoal meal and also inhibited castor oil and MgSO4-induced diarrhoea. The hydroalcoholic and hexane extracts of D. kotschyi (10 and 20 mg/kg) also significantly inhibited the castor oil and MgSO4-induced diarrhoea in mice in comparison with the vehicle-treated control groups. This study confirms that both the hydroalcoholic and hexane extracts of D. kotschyi has antispasmodic and antidiarrhoeal properties in vivo and could be a suitable remedy for treatment of gastrointestinal disorders in which smooth muscle spasm and/or diarrhoea plays a significant roles.
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Affiliation(s)
- Hassan Sadraei
- Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| | - Gholamreza Asghari
- Department of Pharmacognosy and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| | - Farzaneh Shahverdi
- Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
- Department of Pharmacognosy and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
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Sousa NA, Barros FCN, Araújo TS, Costa DS, Souza LKM, Sousa FBM, Leódido ACM, Pacífico DM, Araújo SD, Bezerra FF, Freitas ALP, Medeiros JVR. The efficacy of a sulphated polysaccharide fraction from Hypnea musciformis against diarrhea in rodents. Int J Biol Macromol 2016; 86:865-75. [DOI: 10.1016/j.ijbiomac.2016.02.028] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 02/04/2016] [Accepted: 02/10/2016] [Indexed: 10/22/2022]
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The mechanistic basis of hyperoxaluria following gastric bypass in obese rats. Urolithiasis 2015; 44:221-30. [PMID: 26584912 DOI: 10.1007/s00240-015-0836-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Accepted: 11/02/2015] [Indexed: 01/06/2023]
Abstract
Roux-en-Y gastric bypass (RYGB) surgery is a popular and extremely effective procedure for sustained weight loss in the morbidly obese. However, hyperoxaluria and oxalate kidney stones frequently develop after RYGB and steatorrhea has been speculated to play a role. We examined the effects of RYGB and the role of dietary fat in an obese rat model by measuring fecal fat content and transmural oxalate fluxes across the distal colon compared to sham-operated controls (SHAM). Direct measurements of fecal fat content confirmed that RYGB on a 10 % fat diet excreted 40-fold more fecal fat than SHAM and, on a 40 % fat diet, RYGB excreted sevenfold more fecal fat than SHAM fed similarly. Results from the transport studies revealed a clear effect of high dietary fat (40 %) on colonic oxalate permeability and tissue conductance (G T) with comparable oxalate fluxes in RYGB and in SHAM. Administering a diet containing 10 % fat to both groups distinguished differences between RYGB and SHAM, revealing a 40 % increase in G T in RYGB and a reversal in the direction of net oxalate flux from absorption in SHAM to secretion in RYGB. These changes in colonic oxalate permeability were associated with a fourfold increase in urinary oxalate excretion in RYGB compared to SHAM. Therefore, oxalate solubility and permeability in the RYGB model are promoted by steatorrhea and result in enhanced passive oxalate absorption and hyperoxaluria. To our knowledge, these are the first measurements of intestinal oxalate transport in rats with RYGB.
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Pongkorpsakol P, Wongkrasant P, Kumpun S, Chatsudthipong V, Muanprasat C. Inhibition of intestinal chloride secretion by piperine as a cellular basis for the anti-secretory effect of black peppers. Pharmacol Res 2015; 100:271-80. [PMID: 26297981 DOI: 10.1016/j.phrs.2015.08.012] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2015] [Revised: 08/09/2015] [Accepted: 08/17/2015] [Indexed: 12/31/2022]
Abstract
Piperine is the principal alkaloid in black peppers (Piper nigrum L.), which is a commonly included spice in anti-diarrheal formulations. Piperine has antispasmodic activities, but its anti-secretory effect is not known. Therefore, this study investigated the anti-secretory effect of piperine and its underlying mechanism. Piperine inhibited cAMP-mediated Cl- secretion in human intestinal epithelial (T84) cells, similar to black pepper extract. Intraluminal administration of piperine (2 μg/loop) suppressed cholera toxin-induced intestinal fluid accumulation by ∼85% in mice. The anti-secretory mechanism of piperine was investigated by evaluating its effects on the activity of transport proteins involved in cAMP-mediated Cl- secretion. Notably, piperine inhibited CFTR Cl- channel activity (IC50#8'6#10 μM) without affecting intracellular cAMP levels. The mechanisms of piperine-induced CFTR inhibition did not involve MRP4-mediated cAMP efflux, AMPK or TRPV1. Piperine also inhibited cAMP-activated basolateral K+ channels, but it had no effect on Na+-K+-Cl- cotransporters or Na+-K+ ATPases. Piperine suppressed Ca2+-activated Cl- channels (CaCC) without affecting intracellular Ca2+ concentrations or Ca2+-activated basolateral K+ channels. Collectively, this study indicates that the anti-secretory effect of piperine involves the inhibition of CFTR, CaCC and cAMP-activated basolateral K+ channels. Piperine represents a novel class of drug candidates for the treatment of diarrheal diseases caused by the intestinal hypersecretion of Cl-.
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Affiliation(s)
- Pawin Pongkorpsakol
- Department of Physiology, Faculty of Science, Mahidol University, Rama 6 Road, Ratchathewee, Bangkok, Thailand
| | - Preedajit Wongkrasant
- Department of Physiology, Faculty of Science, Mahidol University, Rama 6 Road, Ratchathewee, Bangkok, Thailand
| | - Saowanee Kumpun
- Department of Chemistry, Faculty of Science and Technology, Suan Sunandha Rajabhat University, Dusit, Bangkok, Thailand
| | - Varanuj Chatsudthipong
- Department of Physiology, Faculty of Science, Mahidol University, Rama 6 Road, Ratchathewee, Bangkok, Thailand; Excellent Center for Drug Discovery, Thailand Center of Excellence for Life Sciences (TCELS), Bangkok, Thailand
| | - Chatchai Muanprasat
- Department of Physiology, Faculty of Science, Mahidol University, Rama 6 Road, Ratchathewee, Bangkok, Thailand; Excellent Center for Drug Discovery, Thailand Center of Excellence for Life Sciences (TCELS), Bangkok, Thailand; Center of Excellence on Environmental Health and Toxicology, Ministry of Education, Bangkok, Thailand.
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19
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Rahman MK, Chowdhury MAU, Islam MT, Chowdhury MA, Uddin ME, Sumi CD. Evaluation of Antidiarrheal Activity of Methanolic Extract of Maranta arundinacea Linn. Leaves. Adv Pharmacol Sci 2015; 2015:257057. [PMID: 26346095 PMCID: PMC4543376 DOI: 10.1155/2015/257057] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 07/07/2015] [Accepted: 07/08/2015] [Indexed: 11/17/2022] Open
Abstract
Diarrhea is one of the most common causes for thousands of deaths every year. Therefore, identification of new source of antidiarrheal drugs becomes one of the most prominent focuses in modern research. Our aim was to investigate the antidiarrheal and cytotoxic activities of methanolic extract of Maranta arundinacea linn. (MEMA) leaves in rats and brine shrimp, respectively. Antidiarrheal effect was evaluated by using castor oil-induced diarrhea, enteropooling, and gastrointestinal motility tests at 200 mg/kg and 400 mg/kg body weight in rats where the cytotoxic activity was justified using brine shrimp lethality bioassay at different concentrations of MEMA. The extract showed considerable antidiarrheal effect by inhibiting 42.67% and 57.75% of diarrheal episode at the doses of 200 and 400 mg/kg, respectively. MEMA also significantly (p < 0.01) reduced the castor oil-induced intestinal volume (2.14 ± 0.16 to 1.61 ± 0.12 mL) in enteropooling test as well as intestinal transit (33.00 to 43.36%) in GI motility test, compared to their respective control. These observed effects are comparable to that of standard drug loperamide (5 mg/kg). On the other hand, in brine shrimp lethality test after 24 h, surviving brine shrimp larvae were counted and LD50 was assessed. Result showed that MEMA was potent against brine shrimp with LD50 value of 420 µg/mL. So the highest dose of 400 µg/mL of MEMA was not toxic to mice. So these results indicate that bioactive compounds are present in methanolic extract of Maranta arundinacea leaves including significant antidiarrheal activity and could be accounted for pharmacological effects.
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Affiliation(s)
- Md. Khalilur Rahman
- Department of Pharmacology, Dongguk University, Gyeongju 780-714, Republic of Korea
| | | | - Mohammed Taufiqual Islam
- Department of Systems Immunology, Kangwon National University, Chuncheon 200-701, Republic of Korea
| | | | - Muhammad Erfan Uddin
- Department of Pharmacy, International Islamic University Chittagong, Chittagong 4203, Bangladesh
| | - Chandra Datta Sumi
- Department of Systems Biotechnology, Chung-Ang University, Anseong 456-756, Republic of Korea
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20
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Galheigo MRU, Prado LCDS, Mundin AMM, Gomes DO, Chang R, Lima AMC, Canabrava HAN, Bispo-da-Silva LB. Antidiarrhoeic effect of Eugenia dysenterica DC (Myrtaceae) leaf essential oil. Nat Prod Res 2015; 30:1182-5. [DOI: 10.1080/14786419.2015.1043633] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Maria Raquel Unterkircher Galheigo
- Laboratory of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, Bloco 2A, Campus Umuarama, Uberlândia Minas, Gerais 38400-902, Brazil
| | - Ligia Carolina da Silva Prado
- Laboratory of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, Bloco 2A, Campus Umuarama, Uberlândia Minas, Gerais 38400-902, Brazil
| | - Angélica Martins Moreira Mundin
- Laboratory of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, Bloco 2A, Campus Umuarama, Uberlândia Minas, Gerais 38400-902, Brazil
| | - Dayane Olímpia Gomes
- Laboratory of Infection Disease, Veterinary Faculty, Federal University of Uberlândia, Av. Pará, 1720, Bloco 2T, Campus Umuarama, Uberlâdia, Minas, Gerais 38400-902, Brazil
| | - Roberto Chang
- Institute of Chemistry, Center of Exact Sciences and Technology, Federal University of Uberlândia, Av. João Naves de Ávila, 2160, Campus Santa Mônica, Uberlândia, Minas, Gerais 38408-100, Brazil
| | - Anna Monteiro Correia Lima
- Laboratory of Infection Disease, Veterinary Faculty, Federal University of Uberlândia, Av. Pará, 1720, Bloco 2T, Campus Umuarama, Uberlâdia, Minas, Gerais 38400-902, Brazil
| | - Hudson Armando Nunes Canabrava
- Laboratory of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, Bloco 2A, Campus Umuarama, Uberlândia Minas, Gerais 38400-902, Brazil
| | - Luiz Borges Bispo-da-Silva
- Laboratory of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, Bloco 2A, Campus Umuarama, Uberlândia Minas, Gerais 38400-902, Brazil
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21
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Medicinal potential of Passiflora foetida L. plant extracts: biological and pharmacological activities. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2014; 12:121-6. [DOI: 10.1016/s2095-4964(14)60017-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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22
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Abraham BP, Sellin JH. Drug-induced, factitious, & idiopathic diarrhoea. Best Pract Res Clin Gastroenterol 2012; 26:633-48. [PMID: 23384808 DOI: 10.1016/j.bpg.2012.11.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2012] [Revised: 11/07/2012] [Accepted: 11/07/2012] [Indexed: 01/31/2023]
Abstract
The aetiology of diarrhoea can often be simple to identify, but in some cases may pose a challenge. The diagnosis of drug-induced diarrhoea can easily be sorted based on timing of the symptom with onset of a new drug. Treatment can vary from simply monitoring and eventual resolution with continuation of the drug, to discontinuation of the offending agent. In cases where a drug cannot always be stopped, additional medications can help control the symptom. Factitious diarrhoea can present a diagnostic challenge if the evaluating physician does not suspect its possibility. Typically a careful history, and in some cases, stool testing can provide clues. The diagnosis of idiopathic diarrhoea is often made when exhaustive testing provides no definite aetiology and the goal of management is supportive care and symptomatic treatment.
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Affiliation(s)
- Bincy P Abraham
- Baylor College of Medicine, 1709 Dryden St., Suite 800, Houston, TX 77030, USA.
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23
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Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors. Proc Natl Acad Sci U S A 2012; 109:9179-84. [PMID: 22615395 DOI: 10.1073/pnas.1201627109] [Citation(s) in RCA: 121] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP(3) prostanoid receptor is specifically activated by ricinoleic acid and that it mediates the pharmacological effects of castor oil. In mice lacking EP(3) receptors, the laxative effect and the uterus contraction induced via ricinoleic acid are absent. Although a conditional deletion of the EP(3) receptor gene in intestinal epithelial cells did not affect castor oil-induced diarrhea, mice lacking EP(3) receptors only in smooth-muscle cells were unresponsive to this drug. Thus, the castor oil metabolite ricinoleic acid activates intestinal and uterine smooth-muscle cells via EP(3) prostanoid receptors. These findings identify the cellular and molecular mechanism underlying the pharmacological effects of castor oil and indicate a role of the EP(3) receptor as a target to induce laxative effects.
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24
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Karmakar U, Sadhu S, Biswas S, Chowdhury A, Shill M, Das J. Cytotoxicity, Analgesic and Antidiarrhoeal Activities of Asparagus racemosus. ACTA ACUST UNITED AC 2012. [DOI: 10.3923/jas.2012.581.586] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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25
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Muanprasat C, Sirianant L, Soodvilai S, Chokchaisiri R, Suksamrarn A, Chatsudthipong V. Novel Action of the Chalcone Isoliquiritigenin as a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Inhibitor: Potential Therapy for Cholera and Polycystic Kidney Disease. J Pharmacol Sci 2012; 118:82-91. [DOI: 10.1254/jphs.11153fp] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2011] [Accepted: 11/10/2011] [Indexed: 10/14/2022] Open
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Medhi B, Kishore K, Singh U, Seth SD. Comparative clinical trial of castor oil and diclofenac sodium in patients with osteoarthritis. Phytother Res 2009; 23:1469-73. [DOI: 10.1002/ptr.2804] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Afroz S, Alamgir M, Khan MTH, Jabbar S, Nahar N, Choudhuri MSK. Antidiarrhoeal activity of the ethanol extract of Paederia foetida Linn. (Rubiaceae). JOURNAL OF ETHNOPHARMACOLOGY 2006; 105:125-30. [PMID: 16298094 DOI: 10.1016/j.jep.2005.10.004] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2005] [Revised: 10/07/2005] [Accepted: 10/07/2005] [Indexed: 05/05/2023]
Abstract
Paederia foetida L. is used as a remedy for diarrhoea and dysentery in Asia, but has not been investigated for its antidiarrhoeal properties. Antidiarrhoeal activity of 90% ethanol extract of Paederia foetida was investigated in this study using castor oil and magnesium sulphate-induced diarrhoea models in mice. The extract significantly increased the latent period of diarrhoea in both the models. In the castor oil study, the purging index (PI) value lowered in 1 h of the study at (100, 250 and 500 mg/kg) doses. The effect continued up to 6-h period only at 500 mg/kg dose. The plant notably reduced the purging index value in a dose-dependent manner in magnesium sulphate-induced diarrhoea. Paederia foetida, in general, reduced the gastrointestinal motility with barium sulphate milk both in 15- and 30-min time intervals. The extract significantly decreased the cisplatin-induced gastrointestinal motility at all doses at both time intervals. The extract also enhanced the morphine-induced reduction of motility at 500 mg/kg dose level at both time intervals. The results suggest that Paederia foetida showed antidiarrhoeal activity by inhibiting intestinal motility and justify its use in traditional medicine.
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Affiliation(s)
- S Afroz
- Department of Pharmacy, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh
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Krishnan S, Rajendran VM, Binder HJ. Apical NHE isoforms differentially regulate butyrate-stimulated Na absorption in rat distal colon. Am J Physiol Cell Physiol 2003; 285:C1246-54. [PMID: 12878493 DOI: 10.1152/ajpcell.00598.2002] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Bicarbonate and butyrate stimulate electroneutral Na absorption via apical membrane Na-H exchange (NHE) in rat distal colon. cAMP downregulates NHE-3 isoform and inhibits HCO3-dependent, but not butyrate-dependent, Na absorption. This study sought to determine whether 1) the apical membrane NHE-2 and NHE-3 isoforms differentially mediated HCO3- and butyrate-dependent Na absorption, and 2) cAMP had different effects on NHE-2 and NHE-3 isoforms. The effect of specific inhibitors of NHE-2 and NHE-3 isoforms (50 microM HOE 694 and 2 microM S3226, respectively) on unidirectional 22Na transepithelial fluxes performed across isolated mucosa from rat distal colon under voltage-clamp conditions was examined. HCO3 stimulation of Na absorption was inhibited by EIPA, a nonspecific inhibitor of all NHE isoforms, by S3226 and dibutyryl cAMP but not by HOE 694. In contrast, butyrate stimulation of Na absorption was not altered by dibutyryl cAMP and was not inhibited by HOE 694 in the absence of dibutyryl cAMP, but in the presence of dibutyryl cAMP was HOE694 sensitive. In contrast, S3226 inhibited butyrate-stimulated Na absorption in the absence of dibutyryl cAMP, but not in its presence. We conclude that 1) HCO3-stimulated Na absorption is mediated solely by NHE-3 isoform, whereas butyrate-stimulated Na absorption is mediated by either NHE-3 or NHE-2 isoform, and 2) dibutyryl cAMP selectively inhibits NHE-3 isoform but stimulates NHE-2 isoform. Dibutyryl cAMP does not inhibit butyrate-stimulated Na absorption as a result of its differential effects on NHE-2 and NHE-3 isoforms.
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Affiliation(s)
- Selvi Krishnan
- Department of Internal Medicine, Yale University, PO Box 208019, New Haven, CT 06520-8019, USA
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Affiliation(s)
- Michael Field
- Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
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31
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Field M. Intestinal ion transport and the pathophysiology of diarrhea. J Clin Invest 2003; 111:931-43. [PMID: 12671039 PMCID: PMC152597 DOI: 10.1172/jci18326] [Citation(s) in RCA: 180] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Michael Field
- Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
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Abstract
Constipation is a common symptom that may be idiopathic or due to various identifiable disease processes. Laxatives are agents that add bulk to intestinal contents, that retain water within the bowel lumen by virtue of osmotic effects, or that stimulate intestinal secretion or motility, thereby increasing the frequency and ease of defecation. Drugs which improve constipation by stimulating gastrointestinal motility by direct actions on the enteric nervous system are under development. Other modalities used to treat constipation include biofeedback and surgery. Laxatives and lavage solutions are also used for colon preparation and evacuation of the bowels after toxic ingestions.
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Affiliation(s)
- L R Schiller
- Baylor University Medical Center, Dallas, Texas 75246, USA.
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Abstract
Laxatives and lavage solutions are used in the treatment of constipation and toxic ingestion and also for preparation of the colon before endoscopic or surgical procedures. Several different categories of agents are available for use. These include bulking agents, osmotic agents, secretagogues and agents with direct effects on epithelial nerve or smooth muscle cells, and lubricating agents. Each category has different pharmacologic effects, side effects, and clinical indications. This review summarizes current information about these agents.
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Affiliation(s)
- L R Schiller
- Baylor University Medical Center, Dallas, Texas 75246, USA
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34
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Capasso F, Mascolo N, Izzo AA, Gaginella TS. Dissociation of castor oil-induced diarrhoea and intestinal mucosal injury in rat: effect of NG-nitro-L-arginine methyl ester. Br J Pharmacol 1994; 113:1127-30. [PMID: 7889264 PMCID: PMC1510485 DOI: 10.1111/j.1476-5381.1994.tb17113.x] [Citation(s) in RCA: 76] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
1. Castor oil (2 ml orally) produced diarrhoea in rats 1-7 h after challenge, which was associated with gross damage to the duodenal and jejunal mucosa. 2. The injury was accompanied by release of acid phosphatase into the gut lumen, indicating cellular injury. 3. Intraperitoneal injection of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 2.5-50 mg kg-1 twice), prevented the diarrhoea. The dose of L-NAME (50 mg kg-1) completely blocked the diarrhoea but increased the release of acid phosphatase and worsened the gross damage. 4. The NO donating compound, isosorbide-5-mononitrate (IMN, 150 mg kg-1 twice) reversed the effects of L-NAME (50 mg kg-1) on castor oil-induced diarrhoea, gross damage and acid phosphatase release. 5. The apparent dissociation of the diarrhoeal and intestinal mucosal damaging effects of castor oil suggest that NO has a protective effect on the rat duodenal and jejunal mucosa, but that NO mediates, in part, the diarrhoea effect of this laxative.
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Affiliation(s)
- F Capasso
- Department of Experimental Pharmacology, University of Naples Federico II, Italy
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35
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Ramakrishna BS, Mathan M, Mathan VI. Alteration of colonic absorption by long-chain unsaturated fatty acids. Influence of hydroxylation and degree of unsaturation. Scand J Gastroenterol 1994; 29:54-8. [PMID: 7907428 DOI: 10.3109/00365529409090437] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Unabsorbed dietary unsaturated fatty acids may cause diarrhea in patients with steatorrhea, but their ability to cause colonic fluid secretion is not known. The present study investigated the effect of several dietary long-chain unsaturated fatty acids on colonic absorption and morphology in the rat colon in vivo. The fatty acids tested induced concentration-dependent net water secretion. The ability of these fatty acids to induce net water secretion varied as follows: linolenic acid (18:3) > linoleic acid (18:2), ricinoleic acid (18:1 OH) > oleic acid (18:1), palmitoleic acid (16:1). Net absorption of sodium and chloride were decreased in fatty acid perfusions. Mucosal activity of sodium potassium adenosine triphosphate and adenyl cyclase were not significantly altered by fatty acids. Epithelial cell damage was noted and correlated with the ability of the fatty acid to induce fluid secretion. Unsaturated fatty acids induce epithelial cell damage and fluid secretion in the colon, their effect being related to the degree of unsaturation.
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Affiliation(s)
- B S Ramakrishna
- Wellcome Trust Research Laboratory, Dept. of Gastrointestinal Sciences, Christian Medical College Hospital, Vellore, India
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36
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Kiyohara T, Okuno M, Nakanishi T, Shinomura Y, Matsuzawa Y. Effect of endothelin 1 on ion transport in isolated rat colon. Gastroenterology 1993; 104:1328-36. [PMID: 8482447 DOI: 10.1016/0016-5085(93)90341-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Endothelin may play a significant role in the regulation of gastrointestinal function because it has a variety of biological activities and because endothelin-like immunoreactivity as well as its specific binding sites have been found in the gastrointestinal tract. This study investigated the secretory effect and mechanism of action of endothelin 1 in mammalian large intestine. METHODS Distal colonic segments from Sprague-Dawley rats were stripped of their muscle layers and mounted in Ussing chambers. The effects of endothelin 1 on short-circuit current in rat colonic mucosa were studied in the absence or presence of specific inhibitors. Transmural unidirectional 22Na+ and 36Cl- fluxes and endothelin 1-induced prostacyclin release were also measured. RESULTS Serosal addition of endothelin 1 evoked a sustained increase in short-circuit current that was significantly reduced by tetrodotoxin or atropine, and virtually abolished by a selective endothelin A receptor antagonist (BQ-123), furosemide, piroxicam, d,I-verapamil, or removal of serosal calcium. Hexamethonium, amiloride, diphenhydramine, or a specific platelet-activating factor antagonist (CV-6209) did not influence the response to endothelin 1. Endothelin 1 significantly decreased net sodium and net chloride absorption and induced a marked increase in prostacyclin release from the serosal surface of stripped colonic mucosa. CONCLUSIONS Endothelin 1 has a secretory effect in rat colon. Its action seems to be mediated by cyclo-oxygenase products and enteric nerves via the activation of an endothelin A receptor.
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Affiliation(s)
- T Kiyohara
- Second Department of Internal Medicine, Osaka University Medical School, Japan
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37
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Mascolo N, Izzo AA, Barbato F, Capasso F. Inhibitors of nitric oxide synthetase prevent castor-oil-induced diarrhoea in the rat. Br J Pharmacol 1993; 108:861-4. [PMID: 7683565 PMCID: PMC1908159 DOI: 10.1111/j.1476-5381.1993.tb13478.x] [Citation(s) in RCA: 73] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
1. Castor oil (2 ml orally) produced copious diarrhoea in rats 3 h after its administration. 2. Pretreatment (intraperitoneal, i.p.) of rats with the NO synthesis inhibitors NG-nitro-L-arginine methyl ester (L-NAME, 1-25 mg kg-1) and NG-monomethyl-L-arginine (L-NMMA, 2.5-100 mg kg-1) inhibited or prevented castor-oil-induced diarrhoea. L-Arginine (150-600 mg kg-1, i.p.) administered to rats pretreated with L-NAME 10 mg kg-1, drastically reduced the antidiarrhoeal activity of L-NAME in a dose-related manner. D-Arginine (900 mg kg-1) did not modify the protection by L-NAME. 3. Pretreatment (i.p.) of rats with L-NAME (2.5-25 mg kg-1) decreased the intestinal fluid accumulation and Na+ secretion induced by castor oil. L-Arginine (600 mg kg-1) but not D-arginine (900 mg kg-1) counteracted the inhibitory effect of L-NAME (10 mg kg-1). 4. L-NAME (10 and 25 mg kg-1) had no significant effect on the intestinal transit in normal rats or those given castor oil. 5. These results provide evidence that nitric oxide (NO) could play an important role in castor-oil-induced diarrhoea.
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Affiliation(s)
- N Mascolo
- Department of Experimental Pharmacology, University of Naples Federico II, Italy
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Thollander M, Hellström PM, Svensson TH. Suppression of castor oil-induced diarrhoea by alpha 2-adrenoceptor agonists. Aliment Pharmacol Ther 1991; 5:255-62. [PMID: 1679667 DOI: 10.1111/j.1365-2036.1991.tb00026.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The effects of systemic administration of alpha 2-adrenoceptor agonists on migrating myoelectric complexes and castor oil-induced diarrhoea of the small intestine were studied in conscious rats. Castor oil (1 mg/kg, intraduodenally) disrupted the migrating myoelectric complexes and induced irregular spiking activity with sporadic bursts of myoelectric activity. This change of motility pattern was present concomitant with diarrhoea 1-2 h after instillation of castor oil and during the whole period of diarrhoea. Pre-treatment with clonidine (5-10 micrograms/kg i.v.) or oxymetazoline (5.6-11.2 micrograms/kg i.v.), a peripherally active alpha 2-agonist, inhibited the irregular spiking induced by castor oil and no diarrhoea occurred during the experimental period of 6 h. Thus, the antidiarrhoeal action of peripherally acting alpha 2-adrenoceptor agonists such as oxymetazoline, may be of clinical value in the treatment of diarrhoea.
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Affiliation(s)
- M Thollander
- Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden
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39
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Hwang TC, Guggino SE, Guggino WB. Direct modulation of secretory chloride channels by arachidonic and other cis unsaturated fatty acids. Proc Natl Acad Sci U S A 1990; 87:5706-9. [PMID: 1696009 PMCID: PMC54396 DOI: 10.1073/pnas.87.15.5706] [Citation(s) in RCA: 100] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The effect of fatty acids on Cl- channels and transepithelial Cl- secretion is investigated. Patch-clamp experiments show that arachidonic acid blocks Cl- channels in a dose-dependent manner. Kinetic analysis shows that the mean open time is decreased 10-fold with 25 microM arachidonic acid. There is a linear relationship between the reciprocal of mean open time and blocker concentration within the range of 1 to 25 microM. The reciprocal of mean blocked time does not change with arachidonic acid concentration. Other cis unsaturated fatty acids, including oleic, linoleic, and ricinoleic acids, demonstrate similar blocks. Trans unsaturated acids such as elaidic acid and saturated fatty acids, including stearic, palmitic, and myristic acids, do not inhibit the channel at 20 microM. Ricinoleic acid decreases short circuit current in T84 cells, a colonic carcinoma cell line that secretes Cl-. Our results suggest that the direct effect of arachidonic and other fatty acids on Cl- secretion is to block Cl- channel current.
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Affiliation(s)
- T C Hwang
- Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205
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40
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Salafsky B, Fusco AC, Li LH, Mueller J, Ellenberger B. Schistosoma mansoni: experimental chemoprophylaxis in mice using oral anti-penetration agents. Exp Parasitol 1989; 69:263-71. [PMID: 2507345 DOI: 10.1016/0014-4894(89)90072-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The ability to prevent schistosomiasis by using an oral chemoprophylactic agent, which acts by preventing cercarial penetration, has been unexplored. We initially examined the effect of praziquantel (PZQ) as such an agent and found that it was moderately effective in blocking cercarial penetration, but that this effect was dependent on the vehicle used to administer the drug. ICR mice were given a total of 200 mg/kg PZQ per os over an 8-hr period in a divided dose of 50 mg/kg/2 hr. At time periods ranging from 0 to 92 hr after the last dose, mice were exposed to approximately 75 75Se-labeled cercariae via the tail. Twenty-four hours later, mice were sacrificed, their tails were removed and subjected to autoradiography, and the percentage of penetration was calculated. Cremophor El, 50% PEG 200, 50% propylene glycol, vegetable oil, and cod liver oil were used as PZQ vehicles. When Cremophor El (ethoxylated castor oil) was used to administer PZQ, a 93% reduction in cercarial penetration was seen at 0 hr and a 98%+ reduction rate was seen from 4 to 24 hr postexposure. However, Cremophor El alone had an essentially equivalent effect on cercarial penetration from 8 to 92 hr after administration. These unexpected results led us to investigate both castor oil and ricinoleic acid (castor oil is 87% ricinoleate as triglyceride) as oral anti-penetration agents. Mice were given the lipids orally by gavage for 7 days. On Day 8, each group of 12 mice was exposed to approximately 75 75Se-radiolabeled cercariae. Castor oil gave protection rate ranging from 90 to almost 100% at an optimal concentration of 0.3 ml/day x 3 or 7 days (approximately 9.8 g/kg/day). These observations suggest that chemoprophylaxis may be possible by dietary supplementation with lipids having anti-penetration activity or by molecules that resemble these lipids.
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Affiliation(s)
- B Salafsky
- University of Illinois College of Medicine, Rockford 61107
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41
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Abstract
This article discusses the various drugs that affect the equine gastrointestinal tract. Drugs that alter intestinal motility, that protect the gastrointestinal tract, and that alter secretions, as well as analgesics, appetite stimulants, and orally administered antimicrobial agents are reviewed.
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Knickelbein RG, Aronson PS, Dobbins JW. Oxalate transport by anion exchange across rabbit ileal brush border. J Clin Invest 1986; 77:170-5. [PMID: 3003149 PMCID: PMC423323 DOI: 10.1172/jci112272] [Citation(s) in RCA: 53] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
This study demonstrates the presence of oxalate transporters on the brush border membrane of rabbit ileum. We found that an inside alkaline (pH = 8.5 inside, 6.5 outside) pH gradient stimulated [14C]oxalate uptake 10-fold at 1 min with a fourfold accumulation above equilibrated uptake at 5 min. 1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonate (disodium salt; DIDS) profoundly inhibited the pH-gradient stimulated oxalate uptake. Using an inwardly directed K+ gradient and valinomycin, we found no evidence for potential sensitive oxalate uptake. In contrast to Cl:HCO3 exchange, HCO3 did not stimulate oxalate uptake more than was seen with a pH gradient in the absence of HCO3. An outwardly directed Cl gradient (50 mM inside, 5 mM outside) stimulated oxalate uptake 10-fold at 1 min with a fivefold accumulation above equilibrated uptake. Cl-stimulated oxalate uptake was largely inhibited by DIDS. Addition of K+ and nigericin only slightly decreased the Cl gradient-stimulated oxalate uptake, which indicates that this stimulation was not primarily due to the Cl gradient generating an inside alkaline pH gradient via Cl:OH exchange. Further, an outwardly directed oxalate gradient stimulated 36Cl uptake. These results suggested that both oxalate:OH and oxalate:Cl exchange occur on the brush border membrane. To determine if one or both of these exchanges were on contaminating basolateral membrane, the vesicle preparation was further fractionated into a brush border and basolateral component using sucrose density gradient centrifugation. Both exchangers localized to the brush border component. A number of organic anions were examined (outwardly directed gradient) to determine if they could stimulate oxalate and Cl uptake. Only formate and oxaloacetate were found to stimulate oxalate and Cl uptake. An inwardly directed Na gradient only slightly stimulated oxalate uptake, which was inhibited by DIDS.
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Kone BC, Racusen LC, Whelton A, Solez K. Renal morphology and function and urine electrolytes in experimental acute renal failure produced by cyclosporine and ischemia. UREMIA INVESTIGATION 1985; 9:119-26. [PMID: 3842027 DOI: 10.3109/08860228509088199] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
It has been difficult to produce a good animal model for cyclosporine nephrotoxicity. It has been suggested that by following 20 minutes of renal ischemia with four daily doses of cyclosporine 60 mg/kg intraperitoneally, one can create a model of reproducible renal failure. We observed excessive mortality (65%), due in part to cyclosporine's CNS effects, with these combined insults in the Munich Wistar rat. In contrast, cyclosporine alone in this dosage produced only 17% mortality and resulted in a similar degree of renal failure. Pair-fed and pair-watered vehicle and saline controls were used. The morphologic changes brought about by the castor oil vehicle of the parenteral cyclosporine solution were qualitatively similar to those brought about by cyclosporine by light microscopy, although the severity of the changes was considerably less in the vehicle-treated groups. However, by electron microscopy, pale lipid vacuoles were seen only in the cyclosporine-treated groups, whereas dense alterations in lysosomes and dilated endoplasmic reticulum also were seen in other groups. Urine sodium determined by flame photometry and urine chloride determined by Saltex reagent strips tended to be high in the initiation phase of cyclosporine-induced acute renal failure and low in the maintenance phase. In animals that developed acute renal failure following the combination of ischemia and cyclosporine, the initial urine sodium and chloride were significantly correlated with the eventual degree of renal failure. The use of Saltex urine chloride sticks in clinical urine samples showed that the readings correlated well with urine sodium and chloride determined by conventional methods, suggesting that these strips may be useful in making a quick diagnosis in the setting of acute renal failure.
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Lückhoff A, Horster M. Hormonal regulation of electrolyte and water transport in the colon. KLINISCHE WOCHENSCHRIFT 1984; 62:555-63. [PMID: 6384647 DOI: 10.1007/bf01728173] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
The colon participates in water and electrolyte homeostasis by the absorption of sodium (Na) and water as well as by potassium (K) secretion. The primary step of colonic transport is the active Na transport via a transcellular route. Steroidal hormones considerably increase Na absorption by utilizing two mechanisms: (1) passive Na entry into the cells in enhanced by an increased membrane permeability; (2) active transport capacity is increased by a stimulation of ATPase synthesis. Mineralocorticoid versus glucocorticoid actions of steroids have not yet been clearly differentiated; parallel influences are possible. Active chloride (Cl) secretion is found in the colon under certain pathological conditions and is induced by a number of factors, e.g., hormones produced by pancreas tumors. Cellular events involve a rise of intracellular cAMP and calcium (Ca) concentrations, and altered Cl permeabilities. Functional changes of colonic epithelial cells caused by hormones assume a significant role in the etiology of diarrhea, as well as in compensatory processes by which an intestinal loss of electrolytes and water is prevented.
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45
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Karlström L, Cassuto J, Jodal M, Lundgren O. The importance of the enteric nervous system for the bile-salt-induced secretion in the small intestine of the rat. Scand J Gastroenterol 1983; 18:117-23. [PMID: 6675168 DOI: 10.3109/00365528309181570] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
We have investigated the possible involvement of the enteric nervous system in the intestinal secretion induced by sodium deoxycholate. Hexamethonium, lidocaine, and tetrodotoxin significantly inhibited the fluid secretion in extrinsically innervated and denervated rat jejunal segments. Atropine had no effect. We conclude that the sodium-deoxycholate-induced intestinal secretion is partly caused by the activation of local nervous reflexes.
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Abstract
The principal anions transported by colonic epithelium are Cl-, HCO3- and organic anions (OA-), particularly acetate, butyrate and pyruvate, these last being formed by microbial degradation of carbohydrate. In the normal absorptive rat colon, Cl- is transported from lumen to plasma both by the transcellular and paracellular pathways. The transcellular route appears to depend on amiloride-insensitive coupling of Na+-Cl- at the mucosal (apical) membrane, the Na+ electrochemical gradient energizing Cl- uptake. Intraluminal [HCO3-] rises as Cl- as absorbed, and a mucosal Cl- -HCO3- exchange carrier has been postulated. In some species (and in distal colon of the rat when sodium-depleted), the putative Na+-Cl- carrier is absent so that Cl- absorption then depends largely on the paracellular electrochemical gradient. Absorption of OA- is independent of the transepithelial p.d., is associated with HCO3- secretion and is considerably reduced by acetazolamide. In the absence of Cl-, OA- supports Na+ absorption but does not depend on it continuing unchanged when the latter is blocked. Colonic epithelium can become secretory and an example of this state is congenital chloridorrhoea in which an elevated transepithelial p.d. is associated with excessive Cl- secretion. Here, it appears that the Na+-Cl- and Cl- -HCO3- carriers are lost and Cl- conductance of the mucosal membrane substantially increased. The transepithelial uphill movements of Cl- or HCO3- in the absorptive and secretory colon appear to depend on coupling to other ionic flows, and there seems to be no need to postulate active transport of these ions.
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47
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Maenz DD, Forsyth GW. Ricinoleate and deoxycholate are calcium ionophores in jejunal brush border vesicles. J Membr Biol 1982; 70:125-33. [PMID: 7186938 DOI: 10.1007/bf01870222] [Citation(s) in RCA: 38] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
The intestinal secretagogues ricinoleate and deoxycholate have been tested for a capacity to form complexes with Ca2+ ions and to affect the passive equilibration of Ca2+ ions across the jejunal brush border membrane. Both of these agents formed butanol-soluble Ca2+ complexes in a model phase distribution system. They also promote the passive uptake and efflux of Ca2+ across brush border vesicles in a concentration-dependent manner. The levels of ricinoleate and deoxycholate that increase the rate of transvesicular Ca2+ movement are in the 100 to 300 microM range. Concentrations as high as 1.0 mM had no significant detergent effects in vesicles as measured by release of entrapped sorbitol. The kinetics of Ca2+ uptake and efflux are similar in brush border vesicles treated with A23187, ricinoleate, or deoxycholate. The influx rates observed in this study were high enough to cause the collapse of a Ca2+ gradient, which had been generated by Ca--Mg ATPase enzyme activity in the brush border membrane. Ricinoleate did not affect Ca--Mg ATPase activity at concentrations used in this study, but deoxycholate was inhibitory, indicating two potential modes for elevation of intracellular Ca2+ content by deoxycholate. When compared with the effects of the Ca2+ ionophore, A23187, it appears that both ricinoleate and deoxycholate could have significant intestinal secretory activity due to this Ca2+ ionophore property. It is also noteworthy that, at least in this model system, potential secretory effects are expressed at concentrations significantly below levels that have been associated with detergent effects or altered epithelial morphology.
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Kelly DG, Kerlin P, Sarr MG, Phillips SF. Ricinoleic acid causes secretion in autotransplanted (extrinsically denervated) canine jejunum. Dig Dis Sci 1981; 26:966-70. [PMID: 7297376 DOI: 10.1007/bf01314756] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
To examine the role of extrinsic nerves and hormones in intestinal secretion of fluid, we studied the effect of ricinoleic acid on absorption by isolated, autotransplanted jejunal loops in four dogs. Compared to perfusion with control solution, the addition of ricinoleic acid caused reversible secretion of water and electrolytes and inhibition of glucose absorption, as previously described in the innervated intestine. In contrast, oral castor oil caused diarrhea but had no effect on absorption from the denervated loop. Thus, the secretory action of ricinoleic acid is maintained without the influence of extrinsic nerves; in addition, further support is added to the proposal that hormones do not mediate secretion in this model. These findings support a local mechanism for the secretion induced by ricinoleic acid.
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Brown BD, Ammon HV. Effect of glucose on jejunal water and solute absorption in the presence of glycodeoxycholate and oleate in man. Dig Dis Sci 1981; 26:710-7. [PMID: 7261835 DOI: 10.1007/bf01316860] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Jejunal perfusion studies were performed in 12 healthy volunteers to study the effects of 14 and 56 mM glucose on fluid secretion induced by 5 mM glycodeoxycholate on 7 mM oleate. Glucose enhanced water absorption under control conditions and reduced water secretion induced by glycodeoxycholate or oleate (P less than 0.01). As has been observed previously, glycodeoxycholate and oleate inhibited glucose absorption (P less than 0.001) and significant linear relationships existed between net water movement and glucose absorption. Glycodeoxycholate also reduced the absorption of 14 mM arabinose (P less than 0.05) and oleate reduced the absorption of 56 mM mannitol (P less than 0.05). Reduced solute absorption in the presence of glycodeoxycholate and oleate, therefore, cannot be attributed to an effect on active transport alone. The relationships between sodium transport and water absorption varied with the glucose concentration in the perfusion solutions. Similarly, the relationships between glucose absorption and sodium absorption varied with glucose concentration. The data suggest that a significant amount of glucose can be absorbed without concomitant absorption of sodium. The data indicate that glucose absorption can stimulate water absorption directly without the mediation of sodium and that water movement follows glucose at a rate which maintains isotonicity.
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50
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Rachmilewitz D, Karmeli F. Laxatives and the cAMP system. Dig Dis Sci 1981; 26:94-5. [PMID: 6161764 DOI: 10.1007/bf01307982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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