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Tabassum N, Spriha SE, Saha P, Rahman FI, Hossain AMA, Rahman SMA. Synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic, anti-inflammatory, antidiarrheal and cytotoxic agents. Heliyon 2024; 10:e40630. [PMID: 39660188 PMCID: PMC11629273 DOI: 10.1016/j.heliyon.2024.e40630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Revised: 10/23/2024] [Accepted: 11/20/2024] [Indexed: 12/12/2024] Open
Abstract
Six heteroarylamide derivatives were synthesized in good yields and screened for several biological activities. Compounds 1-5 demonstrated analgesic activity with percentage inhibition of writhing between 77.10 and 95.79 %, comparable to that of the standard aceclofenac having 91.12 % writhing inhibition. Evaluation of anti-inflammatory activity unveiled that compound 4 exhibited 36.9 %, 64.17 %, 82.9 % and 93.9 % inhibition of paw edema as compared to aceclofenac's inhibition of 35.5 %, 78.6 %, 79.3 % and 91.2 % at the 1st, 2nd, 3rd and 4th hours, respectively. Compounds 5 and 6 exerted considerable antidiarrheal effects with 85.00 % and 71.67 % inhibition of defecation at 25 mg/kg dose, respectively, whereas, the standard loperamide showed 85.00 % inhibition. Compounds 4-6 manifested promising activity in brine shrimp lethality bioassay as well as in trypan blue dye exclusion assay, resulting in 10-20 % cell viability on HeLa cell line and compound 5 was found to have the lowest IC50 of 281.96 μM in the MTT assay. Molecular docking analysis suggested that certain macromolecular targets such as cyclooxygenase-2, muscarinic M3 receptor and matrix metalloproteinase 9 (MMP9) might be involved for the observed activities. As predicted by in silico ADME/T analysis, the compounds also possessed good pharmacokinetic properties.
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Affiliation(s)
- Nazifa Tabassum
- Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Sabiha Enam Spriha
- Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Poushali Saha
- Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Fahad Imtiaz Rahman
- Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, Bangladesh
| | | | - S. M. Abdur Rahman
- Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, 1000, Bangladesh
- Biomedical Research Center, University of Dhaka, Dhaka, 1000, Bangladesh
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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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Obsa Terfa T, Abera Kebede F, Kitessa Beyene M, Tesfaye Abebe T, Basazn Mekuria A, Seid Yesuf J. Evaluation of In Vivo Antidiarrheal Activities of 80% Methanol Extract and Solvent Fractions of Peels of Colocasia esculenta (Araceae). EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2024; 2024:2728282. [PMID: 39035348 PMCID: PMC11259501 DOI: 10.1155/2024/2728282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 04/20/2024] [Accepted: 04/24/2024] [Indexed: 07/23/2024]
Abstract
Background Diarrhea is the common gastrointestinal disorder accounting for 2.5 billion episodes and 1.5 million deaths annually. Limitations and inaccessibility of currently available medications are the main problem associated with treatment of diarrhea. Hence, medicinal plants are usually preferred to manage diarrhea because they may contain constituents with high activity and fewer side effects. Even though the dose, safety, and efficacy of Colocasia esculenta (L.) Schott are not substantiated scientifically, several societies use it for the treatment of diarrhea. Objective This study was targeted at exploring the in vivo antidiarrheal activities of 80% methanol extract and solvent fractions of peels of Colocasia esculenta (L.) Schott in Swiss albino mice. Methods The plant was collected and extracted with 80% methanol, followed by fractionation with distilled water, chloroform, and diethyl ether. Castor oil-induced diarrhea, enteropooling, and motility tests were used to evaluate antidiarrheal activity. The test groups received graded doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg. Negative controls received 10 ml/kg of 2% Tween 80 while positive controls received loperamide (3 mg/kg) or atropine (5 mg/kg). Results The crude and solvent fractions of the plant extract have induced significant effects in reduction of the number and weight of wet stools at all tested doses. However, delay in onset of diarrhea was observed only at 400 mg/kg (P < 0.001) for both crude extract and solvent fractions. In antienteropooling test, 80% methanol extract and solvent fractions have significantly reduced the weight and volume of intestinal contents, especially at 200 mg/kg and 400 mg/kg. Regarding the antimotility test, the crude extract reduced motility at all tested doses, whereas the solvent fractions reduced intestinal motility mainly at 400 mg/kg (P < 0.001). Conclusion The study has revealed that the 80% methanol extract and solvent fractions of the plant possess antidiarrheal activities supporting the traditional antidiarrheal claims of the plant.
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Affiliation(s)
- Temesgen Obsa Terfa
- Department of MedicineCollege of Medicine and Health SciencesJigjiga University, P. O. Box 1020, Jigjiga, Ethiopia
| | - Fekadu Abera Kebede
- Department of NursingCollege of Health SciencesOda Bultum University, Chiro, Ethiopia
| | - Monas Kitessa Beyene
- School of PharmacyCollege of Health and Medical SciencesHaramaya University, P.O. Box 138, Dire Dawa, Ethiopia
| | - Tilahun Tesfaye Abebe
- Department of PharmacyCollege of Medicine and Health SciencesAmbo University, P.O. Box 251, Ambo, Ethiopia
| | - Abebe Basazn Mekuria
- Department of PharmacologySchool of PharmacyCollege of Medicine and Health SciencesUniversity of Gondar, Gondar, Ethiopia
| | - Jibril Seid Yesuf
- Department of PharmacologySchool of PharmacyCollege of Medicine and Health SciencesUniversity of Gondar, Gondar, Ethiopia
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Saptarini NM, Kelutur FJ, Corpuz MJAT. Exploring the Antidiarrheal Properties of Papaya Leaf: Insights In Vivo Study in Mice-Model and In Silico Analysis at M3 Muscarinic Acetylcholine Receptor Interaction. SCIENTIFICA 2024; 2024:1558620. [PMID: 38962530 PMCID: PMC11221971 DOI: 10.1155/2024/1558620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 04/23/2024] [Accepted: 05/13/2024] [Indexed: 07/05/2024]
Abstract
Diarrhea caused by gut motility involves 5-HT3 serotonin receptor (5-HT3R) antagonist, M3 muscarinic acetylcholine receptor (M3-AchR), and H1 histamine receptor (H1R) via their respective agonist. Papaya (Carica papaya L.) leaf is an herbal medicine to treat diarrhea in Indonesia, though this has not yet been proven scientifically. This study aimed to determine the antidiarrheal properties of papaya leaf through in vivo and in silico studies. In the mice model, papaya leaves were infused with distilled water and subjected to in vivo antidiarrheal study using castor oil-induced diarrhea. In silico molecular docking study of nineteen secondary metabolites was carried out on the M3-AchR (PDB ID: 5ZHP) using AutoDock Tools 1.5.6, while ADMET was predicted by pre-ADMET. The results showed that papaya leaf infusion caused a decrease in the total number of feces, an increase in the onset time of diarrhea, a reduction in the frequency of diarrhea, and an increase in the percentage of inhibition of diarrhea. Quercetin 3-rutinoside, a flavonoid glycoside, is potentially an antidiarrheal remedy at M3-AchR. ADMET prediction showed good distribution on the target and was not toxic, but absorption needed to be considered. We concluded that the antidiarrheal activity of papaya leaf infusion was dose-dependent. Based on a molecular docking study, the flavonoid glycoside was very effective as an antidiarrheal remedy. ADMET prediction showed a specific distribution to the target and was not toxic.
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Affiliation(s)
- Nyi Mekar Saptarini
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
| | - Faruk Jayanto Kelutur
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
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Ahmad I, Alotaibi BS, Malak N, Asad F, Ullah B, Nasreen N, Khan A, Chen CC. Antidiarrheal Potential of Viola canescens: In Vivo and In Silico Approaches. Pharmaceuticals (Basel) 2023; 16:ph16040489. [PMID: 37111246 PMCID: PMC10143657 DOI: 10.3390/ph16040489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/17/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
Viola canescens Wall. is an important medicinal plant with reported therapeutic benefits. The current work sought to investigate the antidiarrheal properties of V. canescens extracts both in vivo and in silico. This study applied molecular docking to unravel the molecular mechanism of V. canescens and to find the most effective phytocompounds with antidiarrheal effects. The antidiarrheal activity of V. canescens was assessed utilizing the castor oil-induced diarrhea assay and the charcoal meal assay. Antidiarrheal characteristics were evaluated by measuring parameters such as intestinal motility, fecal score, and hypersecretion. The V. canescens extract had a dose-dependent and statistically significant impact in the charcoal meal assay and castor oil-induced diarrhea assay. In the castor oil-induced diarrhea assay, the ethyl acetate fraction (65.96%) showed the highest percentage of defecation inhibition at the highest dose (300 mg/kg (bw)), followed by the uncorrected crystalline compound (63.83%), crude alkaloids (63.83%), chloroform fraction (63.83%), and crude flavonoids (55.32%), while the aqueous fraction (40.43%) and n-Hexane fraction (42.55%) revealed the lowest antidiarrheal potential. In addition, the molecular docking investigation showed emetine, quercetin, and violanthin, isolated chemicals of V. canescens, to have the highest binding affinity to the target μ and δ opioid receptors with significant inhibitory capacity. These pharmacologically active metabolites in V. canescens were effective in treating diarrhea. This study lends credence to the traditional usage of V. canescens in treating gastrointestinal disorders.
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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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Andargie Y, Sisay W, Molla M, Adela M. Evaluation of In vivo antidiarrheal activity of hydro-methanolic extract of the root of Rumex nepalensis in Swiss Albino mice. Metabol Open 2022; 15:100197. [PMID: 35785136 PMCID: PMC9243151 DOI: 10.1016/j.metop.2022.100197] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/14/2022] [Accepted: 06/16/2022] [Indexed: 11/30/2022] Open
Abstract
Background Natural products have been utilized by human beings for thousands of years to relieve a variety of ailments, including diarrhea. Conventional antidiarrheal drugs are associated with multiple adverse effects and contraindications. Traditionally, Rumex nepalensis by crushing the root, mix with water and then drunk the juice is extensively used for treating diarrhea. However, no scientific research has been done yet to support its antidiarrheal efficacy and safety. Hence, the aim of the study was to evaluate the antidiarrheal activity and safety profile of the plant in mice. Methods The hydro-methanolic extract was extracted through a cold maceration technique using 80% methanol. Castor oil-induced diarrheal, gastro-intestinal transit, and enteropooling models have been employed to assess the antidiarrheal activity of the test extract at doses of 100, 200, and 400 mg/kg. Results The crude root extract caused no mortality at a single limit test dose of 2 g/kg throughout the first 24 h and for the rest of the 14 days. In a castor oil-induced diarrheal model, the hydro-methanolic extract markedly delayed the onset of diarrhea, reduced the weight of wet and total feces at 100 (P<.05), 200 (P<.01), and 400 mg/kg (P<.001) test doses. Meanwhile, at 200 (P<.01) and 400 mg/kg (P<.001) doses, the plant extract considerably lowered the weight and volume of intestinal contents. In the gastro-intestinal transit model, however, a dramatic inhibition in the charcoal meal travel was noticed at 100 (P<.05), 200 (P<.01), and 400 mg/kg (P<.001) test doses. The peak antidiarrheal index was exhibited at the highest dose of the test extract. Conclusion The study speculated that Rumex nepalensis root extract possesses antidiarrheal activity, which could be owing to its inhibitory effect on both gastro-intestinal motility and fluid secretion.
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Affiliation(s)
- Yared Andargie
- School of Pharmacy, College of Medicine and Health Science, Debre Tabor University, Debre Tabor, Ethiopia
| | - Woretaw Sisay
- School of Pharmacy, College of Medicine and Health Science, Debre Tabor University, Debre Tabor, Ethiopia
| | - Mulugeta Molla
- School of Pharmacy, College of Medicine and Health Science, Debre Tabor University, Debre Tabor, Ethiopia
| | - Muluken Adela
- School of Pharmacy, College of Medicine and Health Science, Debre Tabor University, Debre Tabor, Ethiopia
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Dietary polysaccharides from guavira pomace, a co-product from the fruit pulp industry, display therapeutic application in gut disorders. Food Res Int 2022; 156:111291. [DOI: 10.1016/j.foodres.2022.111291] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 04/19/2022] [Accepted: 04/21/2022] [Indexed: 12/22/2022]
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Sarkar KK, Mitra T, Rahman MA, Raja IM, Aktaruzzaman M, Abid MA, Zilani MNH, Roy DN. In Vivo Bioactivities of Hoya parasitica (Wall.) and In Silico Study against Cyclooxygenase Enzymes. BIOMED RESEARCH INTERNATIONAL 2022; 2022:1331758. [PMID: 35528171 PMCID: PMC9071894 DOI: 10.1155/2022/1331758] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 04/04/2022] [Indexed: 11/18/2022]
Abstract
Hoya parasitica (Wall.) is extensively used in traditional medicine for the treatment of various diseases including rheumatism, kidney problems, jaundice, urinary tract disorders, fever, and pain. The present study was designed to explore new lead compound(s) to alleviate pain, pyresis, and diarrhea from methanol, ethyl acetate, and n-hexane extracts of H. parasitica (Wall.) leaves (MHP, EAHP, and NHP, respectively). Analgesic activity of the extracts was assessed through acetic acid induced writhing, tail immersion, and hot plate tests while brewer's yeast-induced pyrexia test was employed for the assessment of antipyretic activity. Besides, castor oil and magnesium sulfate induced diarrheal tests were utilized for the evaluation of antidiarrheal properties. Moreover, in silico study of the isolated compounds was undertaken to seek out best-fit phytoconstituent(s) against cyclooxygenase enzymes. MHP revealed substantial antioxidant activities in different in vitro assays compared to EAHP and NHP. In the acetic acid-induced writhing test, among the extracts, MHP (400 mg/kg) revealed maximum 74.15 ± 1% inhibition of writhing comparable to that of standard (85.77 ± 1.39%). Again, in tail immersion and hot plate tests, higher doses of all the test samples exhibited a significant increase of latent period in a time-dependent manner. In brewer yeast-induced pyrexia test, at 3rd and 4th hour of treatment, significant (P < 0.05) antipyretic action was found in the test samples. In both castor oil and magnesium induced diarrheal tests, MHP at 400 mg/kg showed the highest percent inhibition of diarrhea (68.62 ± 4.74 and 64.99 ± 2.90, respectively). Moreover, molecular docking analysis corroborated the results of the present study. The findings of the present study supported the traditional uses of this plant for the alleviation of pain and fever. Furthermore, hoyasterone was found to be the most effective lead compound as cyclooxygenase enzyme inhibitor.
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Affiliation(s)
- Kishore Kumar Sarkar
- Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Trina Mitra
- Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Md Asibur Rahman
- Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Iqbal Mahmud Raja
- Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Md Aktaruzzaman
- Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Md Ahsan Abid
- Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Md Nazmul Hasan Zilani
- Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
| | - Debendra Nath Roy
- Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore 7408, Bangladesh
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Ethnopharmacological-Based Validation of Polyalthia suberosa Leaf Extract in Neurological, Hyperalgesic, and Hyperactive Gut Disorders Using Animal Models. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:1345006. [PMID: 35222665 PMCID: PMC8872661 DOI: 10.1155/2022/1345006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 11/24/2021] [Accepted: 01/29/2022] [Indexed: 01/02/2023]
Abstract
Polyalthia suberosa (Roxb.) is a plant used to cure coughs, dysentery, fevers, joint aches, rheumatic pain, inflammation, and a variety of skin diseases. The aim of the study was to evaluate the ethyl acetate extract of Polyalthia suberosa (P. suberosa) leaves and their effects on mice for neuropharmacological, analgesic, and antidiarrheal activities. For neurological studies, the hole cross, hole board, open field, and thiopental sodium-induced sleep duration measurement methodologies were used. The castor oil-induced diarrhea inhibition test was used to assess antidiarrheal action, and the acetic acid-induced writhing inhibition test was used to determine analgesic effectiveness. The extract was given in doses of 250 and 500 mg kg−1 body weight. As a standard drug, diazepam at a dosage of 3 mg kg−1 was used. The extract was also given to groups, and sleep time was measured and recorded. The onset of the anxiolytic effect of the extract at both doses was found to be significant (p < 0.001), and sleep time increased to 273 minutes. For assessing analgesic activity, the extract along with standard diclofenac was administered and found to be 55.02 percent and 64.33 percent, respectively, for the extracts, and diclofenac was found to be 67.44 percent (p < 0.001). For antidiarrheal activity, it was compared with the standard drug, loperamide. The decrease for plant extracts was 50.07 percent and 70.06 percent at 250 mg kg−1 and 500 mg kg−1, respectively, whereas it was 85.01 percent for loperamide (3 mg kg−1) (p < 0.00). In this study, it was found that ethyl acetate extract of Polyalthia suberosa leaves had strong CNS depressant, analgesic, and antidiarrheal activities, which indicates that it may be used in contemporary medicine.
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Mariott M, Mariano LNB, Boeing T, Cechinel Zanchett CC, Salamanca E, Bella Cruz A, Giménez A, Cechinel Filho V, da Silva LM. Preparations from Campomanesia reitziana reduce the gastrointestinal motility and castor oil-induced diarrhea in a non-opioid and non-dopaminergic pathway in mice and display antimicrobial activity in vitro. Neurogastroenterol Motil 2022; 34:e14277. [PMID: 34662472 DOI: 10.1111/nmo.14277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/27/2021] [Accepted: 09/20/2021] [Indexed: 01/15/2023]
Abstract
BACKGROUND This study investigated the antidiarrheal potential of the aqueous extract (AECR) and hydroalcoholic extract of Campomanesia reitziana leaves (HECR), its ethyl acetate (EAF) and dichloromethane fractions (DCMF), and myricitrin isolated from EAF. METHODS The total phenols and flavonoids were measured, followed by chromatography and myricitrin isolation. The 2,2-diphenyl-1-picryl-hydrazyl scavenger activity, the cytotoxicity, and the effects on LPS-induced nitrite production in intestinal epithelial cells (IEC-6) were quantified. The effect of HECR, EAF, DCMF, and AECR on intestinal motility (IT), gastric emptying (GE), and castor oil-induced diarrhea in mice was determined, as well as its antimicrobial activity. KEY RESULTS The administration of AECR 10% (10 ml/kg, p.o), but not HECR (300 mg/kg), reduced the GE and IT by 52 and 51%. The EAF and DCMF at 300 mg/kg also reduced IT but did not change GE. Moreover, AECR and EAF, but not DCMF, inhibited the castor oil-induced diarrhea and naloxone or metoclopramide pretreatment did not change these effects. Myricitrin did not change IT and the evacuation index of mice. Finally, the dry residue of AECR inhibited bacterial growth and EAF showed bacteriostatic activity against S. aureus, E. coli, and S. typhimurium and antifungal for C. albicans. However, none of the preparations alter the viability of Giardia spp. trophozoites. CONCLUSIONS The AECR and EAF can be effective to treat diarrhea acting through opioid- or dopaminergic type 2 receptor-independent mechanisms and by its antimicrobial actions.
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Affiliation(s)
- Marihá Mariott
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações QuímicoFarmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Santa Catarina, Brasil
| | - Luísa Nathália Bolda Mariano
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações QuímicoFarmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Santa Catarina, Brasil
| | - Thaise Boeing
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações QuímicoFarmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Santa Catarina, Brasil
| | - Camile Cecconi Cechinel Zanchett
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações QuímicoFarmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Santa Catarina, Brasil
| | - Efrain Salamanca
- Instituto de Investigaciones Fármaco Bioquímicas (IIFB), Universidad Mayor de San Andrés - UMSA, La Paz, Bolívia
| | - Alexandre Bella Cruz
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações QuímicoFarmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Santa Catarina, Brasil
| | - Alberto Giménez
- Instituto de Investigaciones Fármaco Bioquímicas (IIFB), Universidad Mayor de San Andrés - UMSA, La Paz, Bolívia
| | - Valdir Cechinel Filho
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações QuímicoFarmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Santa Catarina, Brasil
| | - Luisa Mota da Silva
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações QuímicoFarmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Santa Catarina, Brasil
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Antidiarrheal Effect of 80% Methanol Extract and Fractions of the Roasted Seed of Coffea arabica Linn (Rubiaceae) in Swiss Albino Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:9914936. [PMID: 35096121 PMCID: PMC8791727 DOI: 10.1155/2022/9914936] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/01/2021] [Accepted: 01/07/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Globally in 2019, diarrhea was the second leading cause of mortality in children, accounting for more than half a million under-five deaths yearly. Several societies use Coffea arabica Linn for the treatment of diarrhea. However, its use is not scientifically validated. OBJECTIVE The study was conducted to evaluate antidiarrheal activity of 80% methanol extract and solvent fractions of roasted seed of Coffea arabica Linn in mice. METHODS Coffea arabica Linn seed was roasted, milled, extracted, and fractionated using hexane, ethyl acetate, and distilled water. Castor oil-induced diarrhea, enteropooling, and motility tests were conducted. Effects on onset, number of feces, weight of feces, fluid content, volume and weight of intestinal content, and motility were evaluated by administering 100 mg/kg, 200 mg/kg, and 400 mg/kg of each extract. Negative controls received 10 ml/kg of the vehicle, and positive controls received either loperamide (3 mg/kg) or atropine (1 mg/kg). Data were analyzed using one-way ANOVA followed by Tukey's post hoc test. RESULTS Ethyl acetate fraction at all tested doses significantly prolonged (p < 0.05) onset of diarrhea. The number and weight of feces were also reduced significantly by crude extract and ethyl acetate fraction. Reduction in fluid content was observed at 200 mg/kg and 400 mg/kg of the crude extract (p < 0.01) and aqueous fraction (p < 0.001) as well as all tested doses of ethyl acetate fraction (p < 0.001). Similarly, the crude extract, ethyl acetate fraction, and aqueous fraction showed a significant reduction in the volume and weight of intestinal content. At 400 mg/kg, the crude extract, hexane fraction, aqueous fraction, and all doses of ethyl acetate fraction showed significant antimotility activity. CONCLUSION The results of this study revealed that the roasted seed of Coffea arabica Linn has antidiarrheal activity.
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Ayalew M, Bekele A, Mengistie MG, Atnafie SA. Evaluation of the antidiarrheal activity of 80% methanol extract and solvent fractions of the leaf of Bersama abyssinica fresen (Melianthaceae) in mice. BMC Complement Med Ther 2022; 22:8. [PMID: 34991582 PMCID: PMC8734363 DOI: 10.1186/s12906-021-03498-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 12/23/2021] [Indexed: 11/10/2022] Open
Abstract
Introduction The use of traditional medicinal plants in the management of diarrhea has long been practiced in Ethiopia. B. abyssinica fresen is one of the plants traditionally used to treat diarrhea whereas an in vivo study had not yet been conducted. Thus, this study aimed to evaluate the antidiarrheal activity of crude extract and solvent fractions of the leaf of B. abyssinica in mice. Methods Cold maceration within 80% methanol was used to extract the leaf powder and extract of the leaf was fractionated using n-hexane, chloroform, and distilled water. The in vivo antidiarrheal activity of crude extracts and solvent fractions were tested in experimental models of castor oil-induced diarrhea, enteropooling, and antimotility test. Five groups each with 6 mice were used under the three antidiarrheal models. Positive controls were treated with loperamide 3 mg/kg and atropine 5 mg/kg and 2% tween 80 was used in the treatment of negative controls. The extract and solvent fractions were administered at doses of 100, 200, and 400 mg/kg. Time of onset of diarrhea, number and weight of total and wet feces, the percent reduction in the number of wet feces, weight and volume of intestinal contents, and percent inhibition of intestinal motility were recorded. Data were analyzed using SPSS version 20. Result Defecation of castor oil-induced diarrheal or loose stools was inhibited (p < 0.01 to p < 0.001) at 200 mg/kg and 400 mg/kg of crude extract and aqueous fraction. The crude extract and the aqueous fraction at three doses (p < 0.01 to p < 0.001), the chloroform fraction at 200 mg/kg and 400 mg/kg (p < 0.01 to p < 0.001), and the n-hexane fraction at 400 mg/kg (p < 0.05) reduced intraluminal fluid accumulation compared with the negative control. Castor oil-induced intestinal motility was significantly suppressed with the three-doses of aqueous fraction (p < 0.05 to p < 0.001), 200 mg/kg and 400 mg/kg of crude extract (p < 0.05 to p < 0.01), 400 mg/kg of chloroform and n-hexane (p < 0.01 to p < 0.001) compared with negative control. Conclusion The crude extract, aqueous, and chloroform fractions of B. abyyssinica leaves have promising anti-diarrheal effects, supporting the plant's traditional use to treat diarrhea.
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Affiliation(s)
- Mihret Ayalew
- Department of Pharmacology, Institute of Health, Jimma University, Jimma, Ethiopia.
| | - Azmeraw Bekele
- Department of Social and Administrative Pharmacy, Institute of Health, Jimma University, Jimma, Ethiopia
| | - Mestayet Geta Mengistie
- Department of Pharmacology, School of Pharmacy, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Seyfe Asrade Atnafie
- Department of Pharmacology, School of Pharmacy, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
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Bibi H, Ali N, Nabi M, Altaf IUK, Shahid M, bukhari SH, Niazi ZR, Shah KU. Flavonoids containing Vitex negundo extract displayed calcium channels blocking property underlying its anti-diarrheal and anti-spasmodic activities. MAIN GROUP CHEMISTRY 2021. [DOI: 10.3233/mgc-210118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Diarrhea is a major health problem and despite of interventions, it remains a substantial cause of mortality and morbidity. In this study, a flavonoids-rich Vitex negundo extract was mechanistically evaluated for its effectiveness in diarrheal diseases. The Vitex negundo ethanolic extract was subjected to extraction for isolation of total flavonoids and qualitative phytochemical analysis. The acute toxicity of flavonoids-extract was done in mice to assess its safety and tolerability. The anti-diarrhoeal activity was determined using the castor oil induced diarrhea mouse model at doses of 10, 30 and 100 mg/kg in relation to loperamide (10 mg/kg, oral). The antispasmodic profile was determined by using cut pieces of rabbit’s jejunum in Tyrode’s solutions, employing acetylcholine (0.03μM) as a tissue stabilizer and verapamil, as a calcium channel blocker. The preliminary qualitative analysis of extract revealed different phytochemicals, in addition to flavonoids. The acute toxicity profile showed that the flavonoids-extract is safe and tolerable (LD50 = 1678 mg/kg). In the tissue experiments, the total flavonoids exhibited an EC50 of 1.52 mg/mL and showed maximum relaxation of spontaneous contractions at 5.0 mg/mL and against high-K + induced contractions at 3 mg/mL (EC50 = 0.43 mg/mL). The spasmolytic activity of total flavonoids was comparable to verapamil which suggests that the activity might be due to the blockade of calcium channels. The flavonoids extract (0.1, 0.3 and 1.0 mg/mL) produced an adequate right shift in the calcium concentration response curve as compared to the control (EC50 value = –2.67 mg/mL), which confirmed that the extract has calcium channel blocking activity.
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Affiliation(s)
- Hadia Bibi
- Department of Pharmacology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, KPK, Pakistan
- Department of Pharmacy, Women Institute of Learning (WIL), Abbottabad, KPK, Pakistan
| | - Niaz Ali
- Department of Pharmacology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, KPK, Pakistan
| | - Muhammad Nabi
- Department of Pharmacology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, KPK, Pakistan
| | | | - Muhammad Shahid
- Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK, Pakistan
| | | | - Zahid Rasul Niazi
- Faculty of Pharmacy, Gomal University, Dera Ismail Khan, KPK, Pakistan
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Evaluation of Antidiarrheal Activity of 80% Methanolic Extract of the Leaves of Cordia africana (Lamiaceae) in Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:3627878. [PMID: 34873407 PMCID: PMC8643234 DOI: 10.1155/2021/3627878] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 10/29/2021] [Accepted: 11/06/2021] [Indexed: 11/26/2022]
Abstract
Background Diarrheal disease is a major cause of morbidity and mortality throughout the world, particularly in developing countries. Currently available drugs are linked with adverse effects, contraindications, and risk of resistance. Traditionally, the leaf concoction of Cordia africana is claimed to be used for diarrhea. However, the safety and efficacy of the leaf extract have not been scientifically approved yet. Therefore, the study was conducted to validate its antidiarrheal activity and safety profile in mice. Method The hydromethanolic extract was obtained by the cold maceration technique in 80% methanol. Phytochemical screening tests were done for secondary metabolites by using standard tests. The antidiarrheal activity of the test extract at the doses of 100, 200, and 400 mg/kg was evaluated by using castor oil-induced diarrheal, gastrointestinal transit, and enteropooling models in mice. Result In an acute toxicity study, there were no visible signs of toxicity and mortality following a single oral administration of 2000 mg/kg. Phytochemical screening tests revealed the presence of alkaloids, saponins, flavonoids, terpenoids, phenols, and tannins. The hydromethanolic extract significantly prolonged the onset of diarrhea and reduced the weight of wet and total feces at 100 (P < 0.01), 200 (P < 0.001), and 400 mg/kg (P < 0.001) in the castor oil-induced diarrheal model. However, in the gastrointestinal transit model, a significant (P < 0.001) reduction in the charcoal meal travel was observed in the middle (200 mg/kg) and higher (400 mg/kg) test doses. Similarly, the extract produced a significant (P < 0.001) reduction in the weight and volume of intestinal contents at the aforementioned doses. Conclusion The study demonstrated that the test extract showed promising antidiarrheal activity. Hence, this study supports its antidiarrheal use in Ethiopian folklore medicine.
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Sammari H, Jedidi S, Selmi H, Rtibi K, Jabri MA, Jridi M, Zouari N, Toumi L, Sebai H. Protective effects of Crataegus azarolus L. berries aqueous extract against castor oil-induced diarrhea, oxidative stress, and inflammation in rat. Neurogastroenterol Motil 2021; 33:e14065. [PMID: 33320393 DOI: 10.1111/nmo.14065] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 10/02/2020] [Accepted: 11/25/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Diarrhea is a multifactorial gastrointestinal disorder responsible for about 5 million deaths annually. The chemical composition, the antioxidant activity of Crataegus azarolus berries aqueous extract (CABAE) as well as its protective effects against castor oil-induced diarrhea, oxidative stress, and inflammation in rat were studied. METHODS Sixty male rats were used and divided into six groups of ten animals in each: Control (C), castor oil (CO), CO+various doses of CABAE (100, 200, and 400 mg/kg b.w., p.o.), and CO+loperamide (LOP, 10 mg/kg b.w., p.o.). KEY RESULTS The CABAE showed relatively high levels of total polyphenols, flavonoids, and tannins. The LC-HRESIMS technique allowed the identification of 5 phenolic compounds and the major component is quinic acid. In vivo studies showed that CABAE protected against castor oil-induced diarrhea and intestinal fluid accumulation. The CABAE counteracted castor oil-induced lipoperoxidation, preserved GSH and thiol groups levels, and prevented the depletion of antioxidant enzyme activities, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). The CABAE administration also protected against castor oil-induced inflammatory markers (ALP and CRP) increase. More importantly, castor oil induced an increase of intracellular mediators, such as hydrogen peroxide, free iron, and calcium, while CABAE pretreatment significantly reversed them to near control levels. CONCLUSION The Crataegus azarolus berries aqueous extract significantly protected against diarrhea due in part to its antioxidant and anti-inflammatory properties.
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Affiliation(s)
- Houcem Sammari
- Unité de Physiologie Fonctionnelle et Valorisation des Bio-Ressources, Institut Supérieur de Biotechnologie de Beja, Université de Jendouba, Beja, Tunisia.,Laboratoire des Ressources Sylvo-Pastorales, Institut Sylvo-Pastoral de Tabarka, Université de Jendouba, Tabarka, Tunisia.,Faculté des Sciences de Bizerte, Université de Carthage, Bizerte, Tunisia
| | - Saber Jedidi
- Unité de Physiologie Fonctionnelle et Valorisation des Bio-Ressources, Institut Supérieur de Biotechnologie de Beja, Université de Jendouba, Beja, Tunisia.,Laboratoire des Ressources Sylvo-Pastorales, Institut Sylvo-Pastoral de Tabarka, Université de Jendouba, Tabarka, Tunisia
| | - Houcine Selmi
- Laboratoire des Ressources Sylvo-Pastorales, Institut Sylvo-Pastoral de Tabarka, Université de Jendouba, Tabarka, Tunisia
| | - Kais Rtibi
- Unité de Physiologie Fonctionnelle et Valorisation des Bio-Ressources, Institut Supérieur de Biotechnologie de Beja, Université de Jendouba, Beja, Tunisia
| | - Mohamed-Amine Jabri
- Unité de Physiologie Fonctionnelle et Valorisation des Bio-Ressources, Institut Supérieur de Biotechnologie de Beja, Université de Jendouba, Beja, Tunisia
| | - Mourad Jridi
- Laboratoire de Génie Enzymatique et de Microbiologie, Ecole Nationale d'Ingénieurs de Sfax, Université de Sfax, Sfax, Tunisia
| | - Nacim Zouari
- Laboratoire de Génie Enzymatique et de Microbiologie, Ecole Nationale d'Ingénieurs de Sfax, Université de Sfax, Sfax, Tunisia
| | - Lamjed Toumi
- Laboratoire des Ressources Sylvo-Pastorales, Institut Sylvo-Pastoral de Tabarka, Université de Jendouba, Tabarka, Tunisia
| | - Hichem Sebai
- Unité de Physiologie Fonctionnelle et Valorisation des Bio-Ressources, Institut Supérieur de Biotechnologie de Beja, Université de Jendouba, Beja, Tunisia
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Methanolic Crude Extract of Hagenia abyssinica Possesses Significant Antidiarrheal Effect: Evidence for In Vivo Antidiarrheal Activity. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:9944629. [PMID: 34055027 PMCID: PMC8143890 DOI: 10.1155/2021/9944629] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/08/2021] [Accepted: 05/10/2021] [Indexed: 11/17/2022]
Abstract
Background Hagenia abyssinica is one of the most commonly used medicinal plants for the treatment of diarrhea in Ethiopia. Therefore, this study aimed to evaluate the antidiarrheal effect of methanol crude extract of H. abyssinica leaves in mice. Methods Acute toxicity testing was conducted using Organization for Economic Cooperation and Development guidelines. The antidiarrheal activity of the crude extract of H. abyssinica was investigated using three animal models such as small intestine transit, enteropooling, and castor oil-induced diarrhea models. The extract was administered at three different doses (100, 200, and 400 mg/kg) to the test groups, while the positive control group received 3 mg/kg of loperamide and the negative control group received 10 ml/kg of vehicle (distilled water). Results The crude extract of H. abyssinica did not exhibit death at the limit dose (2 g/kg) throughout the observation period. In the castor oil-induced model, the crude extract at a dose of 200 and 400 mg/kg exhibited a significant (P < 0.05) antimotility effect as compared to the negative control. The crude extract revealed a significant reduction in the volume and weight of intestinal contents at 200 and 400 mg/kg doses of the extract. Moreover, the highest antidiarrheal index (ADI) was obtained with the dose of 400 mg/kg of crude extract, which was comparable to the standard drug. Conclusion The crude extract of Hagenia abyssinica possesses antidiarrheal activity and supports the traditional use of H. abyssinica for the management of diarrhea.
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Dhawefi N, Jedidi S, Rtibi K, Jridi M, Sammeri H, Abidi C, Zouari N, Sebai H. Antidiarrheal, Antimicrobial, and Antioxidant Properties of the Aqueous Extract of Tunisian Persimmon ( Diospyros kaki Thunb.) Fruits. J Med Food 2021; 24:1100-1112. [PMID: 33872072 DOI: 10.1089/jmf.2020.0202] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Medicinal plants were used to prevent and treat numerous gastrointestinal disorders owing, in part, to their antioxidant capacity. The protective effects of Diospyros kaki fruit aqueous extract (DKFAE) against castor oil (CO)-induced diarrhea was studied. The in vitro antioxidant and antibacterial properties were investigated using colorimetric and biochemical analyses. In vivo, 60 male rats were divided into 6 groups of 10 animals each (n = 10): control (C), CO, CO+various doses of DKFAE (100, 200, and 400 mg/kg, b.w., p.o.), and CO+loperamide (LOP, 10 mg/kg, b.w., p.o.).The DKFAE was rich in tannins and showed interesting antioxidant and antibacterial activities. The liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) analysis resulted in the identification of 16 phenolic compounds, among which quinic acid was the main one. The in vivo study showed that diarrhea was accompanied by an oxidative stress status as measured by an increase of lipid peroxidation, a decrease of glutathione and thiol group levels, as well as antioxidant enzyme activity depletion, such as glutathione peroxidase, superoxide dismutase, and catalase. The DKFAE administration significantly decreased the gastrointestinal transit in a dose-dependent manner. Besides, DKFAE protected against CO-induced diarrhea and intestinal fluid accumulation. Interestingly, DKFAE pretreatment counteracted all the oxidative stress status deregulation induced by CO intoxication. D. kaki fruit could be suggested for its strong protective effect against CO-induced acute diarrhea, which could be explained, in part, to its antimicrobial and antioxidant properties.
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Affiliation(s)
- Nourhène Dhawefi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Béja, Béja, Tunisia
- Faculty of Sciences of Bizerte, University of Carthage, Zarzouna, Tunisia
| | - Saber Jedidi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Béja, Béja, Tunisia
| | - Kais Rtibi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Béja, Béja, Tunisia
| | - Mourad Jridi
- Laboratory of Enzyme Engineering and Microbiology, National Engineering School of Sfax, University of Sfax, Sfax, Tunisia
| | - Houcem Sammeri
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Béja, Béja, Tunisia
- Faculty of Sciences of Bizerte, University of Carthage, Zarzouna, Tunisia
| | - Chaima Abidi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Béja, Béja, Tunisia
| | - Nacim Zouari
- Higher Institute of Applied Biology of Medenine, Unversity of Gabes, Medenine, Tunisia
| | - Hichem Sebai
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Béja, Béja, Tunisia
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Pessoa RF, Duarte Figueiredo IA, Dantas Ferreira SR, Lima de Farias Cavalcanti Silva AR, Marinho Paiva RL, Cordeiro LV, de Oliveira Lima E, Cabrera SP, Sarmento Silva TM, de Andrade Cavalcante F. Investigation of ethnomedicinal use of Commiphora leptophloeos (Mart.) J. B. Gillett (Burseraceae) in treatment of diarrhea. JOURNAL OF ETHNOPHARMACOLOGY 2021; 268:113564. [PMID: 33166628 DOI: 10.1016/j.jep.2020.113564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 10/07/2020] [Accepted: 11/05/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Commiphora leptophloeos (Mart.) J.B. Gillett, popularly known as "imburana", "imburana-de-cheiro" or "imburana-de-espinho", has been used in folk medicine for the treatment of gastrointestinal diseases, such as diarrhea. The indian tribes "Kairir-Shokó and shokó use the bark to treat diarrhea. However, there is no scientific evidence to justify the therapeutic use of this species. AIM OF THE STUDY To investigate the ethnomedicinal use of Commiphora leptophloeos, with respect to the antimicrobial, antisecretory, antimotility and antispasmodic activities of the crude ethanolic extract obtained from its leaves (CL-EtOHL) and the mechanism underlying this action in rodents. MATERIAL AND METHODS In the evaluation of antibacterial and antifungal activities was determined the minimum inhibitory concentration (MIC) of the extract, against different strains of bacteria and fungi. All experimental protocols were approved by the Animal Ethics Committee of the Federal University of Paraíba (045/2016). In addition, behavioral screening and acute toxicity assessment of CL-EtOHL were performed in female mice (n = 6). In the investigation of antidiarrheal activity (n = 6), frequency of defecation and number of liquid stools, were classified during 4 h, and intestinal fluid and transit were measured. In addition, the antispasmodic effect on rat ileum (n = 5) was also investigated. RESULTS The ethanolic extract is rich in flavonoids and the main were identified as C-glycosylated flavonoids (isoorientin, orientin, and vitexin). In the evaluation of antimicrobial and antifungal activity, the extract showed moderate efficacy only against the tested strains of Candida krusei ATCC-6258, Candida parapsilosis ATCC-22019 and Candida glabrata ATCC-90030. The extract had no toxic effect until 2000 mg/kg. In castor oil-induced diarrhea, CL-EtOHL inhibited, in a dose-dependent manner, both total defecation frequency (ED50 = 380.4 ± 145.4 mg/kg) and the number of watery stools (ED50 = 151.2 ± 76.3 mg/kg). The extract showed no effect on fluid accumulation or normal intestinal transit. On the other hand, when the animals were pretreated with castor oil, the extract decreased the distance traveled by the activated charcoal (ED50 = 177.0 ± 50.3 mg/kg). In the investigation of antispasmodic effect, CL-EtOHL antagonized the contractions induced by KCl 30 mM (IC50 = 208.2 ± 25.9 μg/mL) and CCh 10-6 M (IC50 = 95. ± 22.0 μg/mL). To verify the participation of muscarinic receptors in this effect, cumulative carbachol curves were performed in the absence and presence of the extract, and a non-competitive pseudo-irreversible antagonism of these receptors was observed. CONCLUSION The data indicate that ethanol extract obtained from the leaves of Commiphora leptophloeos has an antidiarrheal effect due to inhibition of the intestinal motility and antispasmodic effect, through the antagonism of muscarinic receptors. In addition, we suggest that flavonoids isolated from CL-EtOHL may be responsible for antidiarrheal activity of this extract. This explains its ethnomedicinal use in the treatment of diarrhea.
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Affiliation(s)
- Rayane Fernandes Pessoa
- Programa de Pós-graduação Em Produtos Naturais e Sintéticos Bioativos/Universidade Federal da Paraíba, Brazil
| | | | | | | | | | - Laísa Vilar Cordeiro
- Programa de Pós-graduação Em Produtos Naturais e Sintéticos Bioativos/Universidade Federal da Paraíba, Brazil
| | - Edeltrudes de Oliveira Lima
- Programa de Pós-graduação Em Produtos Naturais e Sintéticos Bioativos/Universidade Federal da Paraíba, Brazil; Departamento de Ciências Farmacêuticas/Universidade Federal da Paraíba, Brazil
| | | | | | - Fabiana de Andrade Cavalcante
- Programa de Pós-graduação Em Produtos Naturais e Sintéticos Bioativos/Universidade Federal da Paraíba, Brazil; Departamento de Fisiologia e Patologia/Universidade Federal da Paraíba, Brazil.
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Antidiarrheal Effect of Zornia brasiliensis Vogel (Leguminosae) on Mice Involves Adrenergic Pathway Activation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:1385606. [PMID: 33727938 PMCID: PMC7939745 DOI: 10.1155/2021/1385606] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Revised: 02/09/2021] [Accepted: 02/19/2021] [Indexed: 12/18/2022]
Abstract
Several secondary metabolites have been isolated from Zornia brasiliensis (Leguminosae), mainly flavonoids. These compounds are known for many pharmacological actions, such as antispasmodic and antidiarrheal. Therefore, we evaluated the antidiarrheal effect of the ethanolic extract obtained from Zornia brasiliensis aerial parts (ZB-EtOHAP), as well as its underlying mechanisms. Castor-oil-induced diarrhea, fluid accumulation, and intestinal transit (normal and castor oil induced) were performed to assess the antidiarrheal, antisecretory, and antipropulsive activities of the extract. The involvement of opioid and adrenergic pathways was also investigated. ZB-EtOHAP inhibited, in a dose-dependent manner, both total defecation frequency and the number of watery stools. The extract showed no effect on fluid accumulation or normal intestinal transit. On the other hand, when the animals were pretreated with castor oil, the extract decreased the distance traveled by the marker in the small intestine. Investigation of the involvement of opioid and adrenergic systems showed that the pharmacological potency of the extract did not change in the presence of naloxone, but it was reduced in the presence of yohimbine. The data indicate that Zornia brasiliensis has an antidiarrheal effect due to inhibition of the intestinal motility through adrenergic pathway activation.
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Mapesa WA, Waweru MP, Bukachi F, Wafula KD. Aqueous Tuber Extracts of Tylosema fassoglense (Kotschy ex Schweinf.) Torre and Hillc. (Fabaceae). Possess Significant In-Vivo Antidiarrheal Activity and Ex-Vivo Spasmolytic Effect Possibly Mediated by Modulation of Nitrous Oxide System, Voltage-Gated Calcium Channels, and Muscarinic Receptors. Front Pharmacol 2021; 12:636879. [PMID: 33796023 PMCID: PMC8007759 DOI: 10.3389/fphar.2021.636879] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 01/29/2021] [Indexed: 12/12/2022] Open
Abstract
Tylosema fassoglense (TFG) is used as an antidiarrheal traditional medicine in Western Kenya. This study aimed to investigate the antidiarrheal activity of its aqueous extracts in-vivo and the putative mechanism (s) of action ex-vivo using Sprague-Dawley rats and New Zealand white rabbits respectively. The in-vivo antidiarrheal effects of the extract were evaluated in castor oil-induced diarrhea, the castor oil-induced enteropooling, and phenol red gastric motility tests. On the other hand, isolated rabbit's jejunal segments were used to evaluate the spasmolytic effect of TFG on spontaneous contraction, in acetylcholine-induced contraction, in presence of 80mMK+, calcium chloride-induced contraction as well as in presence of the following antagonists: naloxone, methylene blue, L-NAME, prazosin, and propranolol in the ex-vivo studies. The data were express as Mean ± S.E.M and analyzed by one-way ANOVA and Tukey's post hoc test in cases of significance which was set at p < 0.05. The extract was phytochemically characterized using Liquid chromatography Mass spectroscopy (LC-MS).The extract possessed significant inhibitory effect in the in-vivo experiments. The extract exhibited significant spasmolytic effect on both spontaneous contraction and in jejunal segment pre-contracted acetylcholine as well as in presence of 80mMK+ solution. It also attenuated the spasmogenic effect of various concentration of calcium chloride. The extract's spasmolytic effect was, however, significantly attenuated in presence of several antagonists (methylene blue and L-NAME) but the adrenergic blockers (prazosin and propranolol) had no significant effect in the ex-vivo studies. LC-MS identified thirty compounds where Proathocyanidin (11.54%), Syringic acid (7.30%), and 4-Hydroxybenzoic acid (6.19%) had the highest percentage abundance. In conclusion, the results obtained in this study partially validate the traditional uses of the tubers of this plant species as an antidiarrheal. These antidiarrheal effects are probably mediated via modulation of nitrous oxide pathway, voltage gated calcium channels, and muscarinic receptors.
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Affiliation(s)
- Washika Amos Mapesa
- Department of Medical Physiology, School of Medicine, University of Nairobi, Nairobi, Kenya
| | - Mwangi Peter Waweru
- Department of Medical Physiology, School of Medicine, University of Nairobi, Nairobi, Kenya
| | - Frederick Bukachi
- Department of Medical Physiology, School of Medicine, University of Nairobi, Nairobi, Kenya
| | - Kayaja David Wafula
- Department of Medical Physiology, School of Medicine, University of Nairobi, Nairobi, Kenya
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Muhammad N, Ullah S, Rauf A, Atif M, Patel S, Israr M, Akbar S, Shehzad O, Saeed M, Bawazeer S, Uddin MS, Derkho M, Shariati MA, Mubarak MS. Evaluation of the anti-diarrheal effects of the whole plant extracts of Cuscuta reflexa Roxb in pigeons. Toxicol Rep 2021; 8:395-404. [PMID: 33717992 PMCID: PMC7921875 DOI: 10.1016/j.toxrep.2021.02.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 02/16/2021] [Accepted: 02/20/2021] [Indexed: 01/22/2023] Open
Abstract
The antidiarrheal activity of C. reflexa was evaluated in pigeons using the juice, aqueous, and methanol extracts. The antidiarrheal effect of C. reflexa was evaluated using different reported research models. The juice, aqueous, and methanol extract of C. reflexa exhibit significant anti-motility and anti-secretory potential. Background Cuscuta reflexa (dodder) belonging to the family Convolvulaceae has many ethno-medicinal uses such as antidiarrheal and antiemetic. This plant has been employed to treat diarrhea, where the antidiarrheal use of this plant is well established in different communities around the world without scientific bases. In addition, the antibacterial, anthelmintic, anticholinergic, and antihistaminic effects of this parasitic vine are partly responsible for the folkloric antidiarrheal use of this plant. In the present study, the antidiarrheal activity of C. reflexa was evaluated in pigeons (Columba livia) using the juice (JCR), aqueous (CRAE), and methanol (CRME) extracts. Methods The antidiarrheal effect of C. reflexa was evaluated using different reported research models, with few modifications. In pigeons, diarrhea was induced by administration of castor oil (6 mL/kg, PO), ampicillin (250 mg/kg, IP), magnesium sulfate (2 gm/kg, PO), and cisplatin (6 mg/kg, IV). In these experiments, loperamide (2 mg/kg, IM) was used as a positive control, whereas JCR (1 mL/kg (1%) and 1 mL/kg (2%), CRAE (50, 100 and 200 mg/kg) and CRME (50, 100 and 200 mg/kg) were administered intramuscularly at different doses into each pigeon in the test groups. Results In addition to cisplatin-induced diarrhea, all paradigms tested gave significant results (P < 0.01). The JCR, at different doses, exhibited a significant (p < 0.01) a dose-dependent antidiarrheal effect on both the frequency and the onset of diarrhea. Similarly, CRAE and CRME, at doses of 100 and 200 mg/kg, showed considerable (p < 0.001) inhibition against the onset and frequency of diarrhea. On the other hand, JCR, CRAE, and CRME exerted significant effects (p < 0.001) on the percentage inhibition (PI) of diarrhea and gastrointestinal charcoal transit in a dose-dependent manner. In this respect, the maximum PI (p < 0.01) of JCR, CRAE, and CRME in different experimental paradigms was 43.13, 49.14, and 55.99 %, respectively. Conclusions Taken all together, results from this study reveal that the juice, aqueous, and methanol extract of C. reflexa exhibit significant anti-motility and anti-secretory potential. These findings may explain the medicinal use of C. reflexa in folk medicine as an antidiarrheal medicinal plant.
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Affiliation(s)
- Naveed Muhammad
- Department of Pharmacy, Abdul Wali Khan University, Mardan, KPK, Pakistan
| | - Sana Ullah
- Department of Pharmacy, Abdul Wali Khan University, Mardan, KPK, Pakistan
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, 23561, KPK, Pakistan
- Corresponding author at: Department of Chemistry, University of Swabi, KPK, Pakistan.
| | - Muhammad Atif
- Department of Chemistry, University of Swabi, Anbar, 23561, KPK, Pakistan
| | - Seema Patel
- Bioinformatics and Medical Informatics Research Center, San Diego State University, San Diego, 92182, USA
| | - Muhammad Israr
- Pakistan Science, Foundation, Islamabad, Islamabad, Pakistan
| | - Sajid Akbar
- Abbotabad University of Science and Technology, Abbotabad, KPK, Pakistan
| | - Omer Shehzad
- Department of Pharmacy, Abdul Wali Khan University, Mardan, KPK, Pakistan
| | - Muhammad Saeed
- Department of Pharmacy, University of Peshawar, Peshawar, KPK, Pakistan
| | - Saud Bawazeer
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah, P.O. Box 42, Saudi Arabia
| | - Md. Sahab Uddin
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh
- Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
| | - Marina Derkho
- South-Ural State Agrarian University, Troitsk, Russian Federation
| | - Mohammad Ali Shariati
- K.G. Razumovsky Moscow State University of Technologies and Management (the First Cossack University), Moscow, Russian Federation
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Evaluation of In Vivo Antidiarrheal Activity of Solvent Fractions of Hagenia abyssinica (Rosaceae) in Swiss Albino Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:8828331. [PMID: 33628317 PMCID: PMC7896859 DOI: 10.1155/2021/8828331] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 02/03/2021] [Accepted: 02/04/2021] [Indexed: 12/11/2022]
Abstract
Background Ethiopia has several medicinal plants that have been used for their antidiarrheal activity. Hagenia abyssinica is the most commonly used medicinal plant for the management of diarrhea in Ethiopia. Thus, this study's aim is to investigate the antidiarrheal effect of solvent fractions of H. abyssinica. Methods Antidiarrheal activity of extract fractions obtained from different solvents was evaluated by using small intestine transit, enteropooling, and castor oil-induced diarrhea animal models. In all animal models, the solvent fractions treated groups were treated with three different doses (100 mg/kg, 200 mg/kg, and 400 mg/kg) of the solvent fractions, while the negative control group was treated with a vehicle (distilled water), and positive control group was treated with loperamide. Results The acute toxicity test revealed that the LD50 of H. abyssinica is > 2000 mg/kg. In castor oil-induced, the solvent fractions of H. abyssinica (at 200 mg/kg and 400 mg/kg) significantly (P < 0.05–0.001) prolonged the stool frequency, reduced the weight of feces, and delayed diarrheal onset time as compared with the negative control group. The fractions produced a significant (P < 0.05) antimotility effect at the doses of 200 mg/kg and 400 mg/kg as compared to the negative control. All solvent fractions at the middle and higher doses showed a statistically significant dose-dependent reduction in the volume of intestinal contents and weight of the feces. However, the solvent fractions of H. abyssinica at a dose of 100 mg/kg failed to produce a statistically significant activity in all parameters (number of wet feces, the onset of diarrhea, and number of total feces) when compared with the negative control group. Conclusion The extract fractions obtained from different solvents have shown significant antidiarrheal activity. Thus, this finding supports the claimed traditional use of H. abyssinica leaves for the treatment of diarrhea.
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Pereira JC, Figueiredo IAD, de Oliveira FRMB, Ferreira SRD, Aires Moreno GT, da Silva TMS, Pinheiro UDS, Santos BVDO, da Silva BA, Cavalcante FDA. Oceanapia magna Sponge Presents Dual Effect on the Gastrointestinal Motility of Rodents: In Vitro and In Vivo Assays. Front Pharmacol 2021; 11:572574. [PMID: 33424588 PMCID: PMC7793637 DOI: 10.3389/fphar.2020.572574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 11/23/2020] [Indexed: 11/13/2022] Open
Abstract
Oceanapia magna Santos-Neto, Nascimento, Cavalcanti and Pinheiro sponges are distributed across tropical worldwide seas. Some studies of marine products have shown interesting activities in smooth muscle models. Hence, we assessed the effect of the ethanolic extract of Oceanapia magna. (OC-EtOH) on acute toxicity and gastrointestinal motility (in vitro and in vivo) in rodent models. On guinea pig ileum, OC-EtOH induced a concentration dependent contraction on basal tonus, which was not inhibited by atropine, but in the presence of pyrilamine or verapamil, the effect was antagonized. Contrastingly, on KCl- or histamine-induced contractions, OC-EtOH presented a transient contraction followed by a concentration-dependent relaxation. Moreover, OC-EtOH presented a relaxant profile on cumulative curves to CaCl2 and tonic contraction induced by S-(-)-BayK8644, through Cav blockade. The acute toxicity assay showed that OC-EtOH (2,000 mg/kg, p.o.) did not present any sign of toxicity in female mice. Additionally, OC-EtOH presented antidiarrheal effect in mice, increased the intestinal normal transit and reduced the castor oil-induced intestinal transit. Thus, OC-EtOH presented a dual effect on guinea pig ileum promoting contraction through activation of H1 and CaV, and relaxation through CaV blockade, besides the effect on upper gastrointestinal transit in mice, showing a potential medicinal use of this sponge in intestinal diseases such as diarrhea.
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Affiliation(s)
- Joedna Cavalcante Pereira
- Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, João Pessoa, Brazil
| | | | | | - Sarah Rebeca Dantas Ferreira
- Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, João Pessoa, Brazil
| | | | | | | | - Barbara Viviana de Oliveira Santos
- Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, João Pessoa, Brazil.,Departmento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa, Brazil
| | - Bagnólia Araújo da Silva
- Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, João Pessoa, Brazil.,Departmento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa, Brazil
| | - Fabiana de Andrade Cavalcante
- Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, João Pessoa, Brazil.,Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba, João Pessoa, Brazil
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Akuodor GC, Essiet GA, Ekenjoku JA, Udoh FV, Ogiji ED, Ibiam GA, Nnorom FO. Antidiarrhoael and antimicrobial effects of ethanol root bark extract from Salacia lehmbachii. JOURNAL OF HERBMED PHARMACOLOGY 2021. [DOI: 10.34172/jhp.2021.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Introduction: The roots of Salacia lehmbachii are used in Nigerian folklore medicine without scientific basis. The present study was aimed to investigate the antidiarrheal and antimicrobial activities of the ethanol extract of S. lehmbachii root bark. Methods: The antidiarrheal activity was examined using castor oil induced diarrhoea method. The ethanol root bark extract effects on intestinal transit time and enteropooling were also evaluated in rats, while antimicrobial activity was conducted on selected microorganisms. The acute toxicity test and phytochemical screening of the extract were also carried out. Results: The extract produced significant (P < 0.05) dose dependent protection on rats against castor oil induced diarrhoea. The extract inhibited intestinal transit time and caused significant dose related inhibition of castor oil induced enteropooling in rats, comparable to the standard drug, atropine (P < 0.05). The root bark extract significantly and dose dependently delayed the onset of castor oil induced diarrhoea, reduced the frequency of defecation and decreased the severity of diarrhoea in rats. S. lehmbachii ethanol root bark extract significantly and dose dependently decreased the volume of intestinal fluid accumulation in the castor oil induced enteropooling. The extract also significantly inhibited the growth of test organisms. The acute toxicity test produced no lethality in rats, whereas the phytochemical analysis revealed the presence of alkaloids, saponins, tannins, flavonoids, terpenoids, steroids, cardiac glycosides, resins and balsam. Conclusion: The results of this study confirm the ethnomedicinal use of S. lehmbachii root bark as a valuable natural agent for the treatment of diarrhoea and microbial infections.
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Affiliation(s)
- Godwin Christian Akuodor
- Department of Pharmacology and Therapeutics, Faculty of Medicine, College Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nigeria
| | - Grace Akanimo Essiet
- Department of Pharmacology, College of Medical Sciences, University of Calabar, Calabar, Nigeria
| | | | - Francis Vincent Udoh
- Department of Pharmacology, College of Medical Sciences, University of Calabar, Calabar, Nigeria
| | - Emeka Donald Ogiji
- Department of Pharmacology and Therapeutics, Faculty of Medicine, Ebonyi State University, Abakaliki, Nigeria
| | - Gideon Ama Ibiam
- Department of Medical Laboratory Science, Faculty of Health Sciences and Technology, Ebonyi State University, Abakaliki, Nigeria
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Pessoa MLDS, Silva LMO, Araruna MEC, Serafim CADL, Júnior EBA, Silva AO, Pessoa MMB, Neto HD, Lima EDO, Batista LM. Antifungal activity and antidiarrheal activity via antimotility mechanisms of (-)-fenchone in experimental models. World J Gastroenterol 2020; 26:6795-6809. [PMID: 33268962 PMCID: PMC7684460 DOI: 10.3748/wjg.v26.i43.6795] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 08/12/2020] [Accepted: 10/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND (-)-Fenchone is a bicyclic monoterpene present in essential oils of plant species, such as Foeniculum vulgare and Peumus boldus, used to treatment of gastrointestinal diseases. Pharmacological studies report its anti-inflammatory, antioxidant, and antinociceptive activity.
AIM To investigate antidiarrheal activity related to gastrointestinal motility, intestinal secretion and antimicrobial activity.
METHODS A castor oil-induced diarrhea model was used to evaluate antidiarrheal activity. Intestinal transit and gastric emptying protocols were used to assess a possible antimotility effect. Muscarinic receptors, presynaptic α2-adrenergic and tissue adrenergic receptors, KATP channels, nitric oxide were investigated to uncover antimotility mechanisms of action and castor oil-induced enteropooling to elucidate antisecretory mechanisms. The antimicrobial activity was evaluated in the minimum inhibitory concentration model, the fractional inhibitory concentration index using the (-)-fenchone association method with standard antifungal agents.
RESULTS (-)-Fenchone (75, 150 and 300 mg/kg) showed antidiarrheal activity, with a significant decrease in the evacuation index. This activity is possibly related to a percentage of reduced intestinal transit (75, 150 and 300 mg/kg). The antimotility effect of (-)-fenchone decreased in the presence of pilocarpine, yohimbine, propranolol, L-NG-nitroarginine methyl ester or glibenclamide. In the enteropooling model, no reduction in intestinal fluid weight was observed. (-)- Fenchone did not show antibacterial activity; on the other hand, inhibits the growth of strains of fungi with a minimum fungicide concentration of 32 μg/mL. However, when it was associated with amphotericin B, no synergism was observed.
CONCLUSION The antidiarrheal effect of (-)-fenchone in this study involves antimotility effect and not involve antisecretory mechanisms. (-)-Fenchone presents antifungal activity; however, it did not show antibacterial activity.
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Affiliation(s)
- Michelle Liz de Souza Pessoa
- Department of Pharmaceutical Sciences, IPeFarM, Federal University of Paraíba, João Pessoa 58051-970, Paraíba, Brazil
| | | | - Maria Elaine Cristina Araruna
- Department of Pharmaceutical Sciences, IPeFarM, Federal University of Paraíba, João Pessoa 58051-970, Paraíba, Brazil
| | | | - Edvaldo Balbino Alves Júnior
- Department of Pharmaceutical Sciences, IPeFarM, Federal University of Paraíba, João Pessoa 58051-970, Paraíba, Brazil
| | - Alessa Oliveira Silva
- Department of Pharmaceutical Sciences, IPeFarM, Federal University of Paraíba, João Pessoa 58051-970, Paraíba, Brazil
| | | | - Hermes Diniz Neto
- Department of Pharmaceutical Sciences, IPeFarM, Federal University of Paraíba, João Pessoa 58051-970, Paraíba, Brazil
| | - Edeltrudes de Oliveira Lima
- Department of Pharmaceutical Sciences, IPeFarM, Federal University of Paraíba, João Pessoa 58051-970, Paraíba, Brazil
| | - Leônia Maria Batista
- Postgraduate Program in Natural and Synthetic Bioactive Products, Universidade Federal da Paraiba, João Pessoa 58051-900, Brazil
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Rudra S, Tahamina A, Emon NU, Adnan M, Shakil M, Chowdhury MHU, Barlow JW, Alwahibi MS, Soliman Elshikh M, Faruque MO, Uddin SB. Evaluation of Various Solvent Extracts of Tetrastigma leucostaphylum (Dennst.) Alston Leaves, a Bangladeshi Traditional Medicine Used for the Treatment of Diarrhea. Molecules 2020; 25:molecules25214994. [PMID: 33126608 PMCID: PMC7662597 DOI: 10.3390/molecules25214994] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/24/2020] [Accepted: 10/26/2020] [Indexed: 12/23/2022] Open
Abstract
Tetrastigma leucostaphylum (TL) is an important ethnic medicine of Bangladesh used to treat diarrhea and dysentery. Hence, current study has been designed to characterize the antidiarrheal (in vivo) and cytotoxic (in vitro) effects of T. leucostaphylum. A crude extract was prepared with methanol (MTL) and further partitioned into n-hexane (NTL), dichloromethane (DTL), and n-butanol (BTL) fractions. Antidiarrheal activity was investigated using castor oil induced diarrhea, enteropooling, and gastrointestinal transit models, while cytotoxicity was evaluated using the brine shrimp lethality bioassay. In antidiarrheal experiments, all doses (100, 200, and 400 mg/kg) of the DTL extract significantly reduced diarrheal stool frequency, volume and weight of intestinal contents, and gastrointestinal motility in mice. Similarly, in the cytotoxicity assay, all extracts exhibited activity, with the DTL extract the most potent (LC50 67.23 μg/mL). GC-MS analysis of the DTL extract identified 10 compounds, which showed good binding affinity toward M3 muscarinic acetylcholine, 5-HT3, Gut inhibitory phosphodiesterase, DNA polymerase III subunit alpha, and UDP-N-acetylglucosamine-1 carboxyvinyltransferase enzyme targets upon molecular docking analysis. Although ADME/T analyses predicted the drug-likeness and likely safety upon consumption of these bioactive compounds, significant toxicity concerns are evident due to the presence of the known phytotoxin, 2,4-di-tert-butylphenol. In summary, T. leucostaphylum showed promising activity, helping to rationalize the ethnomedicinal use and importance of this plant, its safety profile following both acute and chronic exposure warrants further investigation.
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Affiliation(s)
- Sajib Rudra
- Ethnobotany and Pharmacognosy Lab, Department of Botany, University of Chittagong, Chattogram 4331, Bangladesh; (S.R.); (A.T.); (M.S.); (M.H.U.C.)
| | - Afroza Tahamina
- Ethnobotany and Pharmacognosy Lab, Department of Botany, University of Chittagong, Chattogram 4331, Bangladesh; (S.R.); (A.T.); (M.S.); (M.H.U.C.)
| | - Nazim Uddin Emon
- Department of Public Health, School of Science and Technology, Bangladesh Open University, Gazipur 1705, Dhaka, Bangladesh;
| | - Md. Adnan
- Department of Bio-Health Technology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Korea;
| | - Mohammad Shakil
- Ethnobotany and Pharmacognosy Lab, Department of Botany, University of Chittagong, Chattogram 4331, Bangladesh; (S.R.); (A.T.); (M.S.); (M.H.U.C.)
| | - Md. Helal Uddin Chowdhury
- Ethnobotany and Pharmacognosy Lab, Department of Botany, University of Chittagong, Chattogram 4331, Bangladesh; (S.R.); (A.T.); (M.S.); (M.H.U.C.)
| | - James W. Barlow
- Department of Chemistry, Royal College Surgeons, Dublin D02YN77, Ireland;
| | - Mona S. Alwahibi
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; (M.S.A.); (M.S.E.)
| | - Mohamed Soliman Elshikh
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; (M.S.A.); (M.S.E.)
| | - Mohammad Omar Faruque
- Ethnobotany and Pharmacognosy Lab, Department of Botany, University of Chittagong, Chattogram 4331, Bangladesh; (S.R.); (A.T.); (M.S.); (M.H.U.C.)
- Correspondence: (M.O.F.); (S.B.U.); Tel.: +88-018-1839-7345 (M.O.F.); +88-017-1106-5377 (S.B.U.)
| | - Shaikh Bokhtear Uddin
- Ethnobotany and Pharmacognosy Lab, Department of Botany, University of Chittagong, Chattogram 4331, Bangladesh; (S.R.); (A.T.); (M.S.); (M.H.U.C.)
- Correspondence: (M.O.F.); (S.B.U.); Tel.: +88-018-1839-7345 (M.O.F.); +88-017-1106-5377 (S.B.U.)
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de Souza ILL, de Vasconcelos MA, da Silva ADS, Silva PCB, Veloso CAG, de Araújo DIAF, Costa VCDO, Pessôa HLF, Tavares JF, da Silva MS, da Silva BA, Cavalcante FDA. Toxicological and Pharmacological Activities of Leptohyptis macrostachys (Benth.) Harley and J.F.B.Pastore (Lamiaceae) on Intestinal Smooth Muscle. Front Pharmacol 2020; 11:1042. [PMID: 32754035 PMCID: PMC7366869 DOI: 10.3389/fphar.2020.01042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 06/26/2020] [Indexed: 11/13/2022] Open
Abstract
Leptohyptis macrostachys, previously known as Hyptis macrostachys Benth., is used in folk medicine to relieve the symptoms of asthma, cough, and bronchitis. Recently, we showed that the ethanol extract obtained from Leptohyptis macrostachys has selective spasmolytic activity on guinea pig ileum. Therefore, the aim of this study was to characterize the spasmolytic mechanism of this extract, investigated whether it presents toxicological and antidiarrheal activities. Therefore, the crude ethanolic extract of Leptohyptis macrostachys was analyzed by high-performance liquid chromatographic-diode array detection (HPLC-DAD). The spasmolytic effect was evaluated on guinea pig ileum, toxicological activity using rats and antidiarrheal activity using male and female mice. In HPLC-DAD analysis, Rosmarinic acid (5.44%) was the most abundant phenolic compound, being considered as a chemical marker. The spasmolytic potency of the extract on histamine-induced contraction was reduced in the presence of 1 mM TEA+, a selective big-conductance K+ channels blocker (BKCa). The extract produces a dose-dependent antidiarrheal activity, inhibiting equipotently defecation frequency and liquid stool formation. In addition, the extract has inhibited in a dose-dependent manner both castor oil-induced intestinal transit and intestinal fluid content. Thus, the spasmolytic activity of the extract involves positive modulation of BKCa and its antidiarrheal activity is related to inhibition of intestinal motility and secretion.
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Affiliation(s)
- Iara Leão Luna de Souza
- Departamento de Ciências Biológicas e Saúde, Universidade Estadual de Roraima, Boa Vista, Brazil
| | | | - Anne Dayse Soares da Silva
- Programa de Pós-graduação em Química e Biotecnologia, Instituto de Química, Universidade Federal de Alagoas, Maceió, Brazil
| | | | | | | | | | - Hilzeth Luna Freire Pessôa
- Departamento de Biologia Molecular, Centro de Ciências Exatas e da Natureza, Universidade Federal da Paraíba, João Pessoa, Brazil
| | - Josean Fechine Tavares
- Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, João Pessoa, Brazil
- Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Brazil
| | - Marcelo Sobral da Silva
- Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, João Pessoa, Brazil
- Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Brazil
| | - Bagnólia Araújo da Silva
- Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, João Pessoa, Brazil
- Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Brazil
| | - Fabiana de Andrade Cavalcante
- Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, João Pessoa, Brazil
- Departamento de Fisiologia e Patologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Brazil
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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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Jedidi S, Rtibi K, Selmi S, Aloui F, Selmi H, Wannes D, Sammari H, Dhawefi N, Chaâbane A, Sebai H. Phytochemical/Antioxidant Properties and Individual/Synergistic Actions of Salvia officinalis L. Aqueous Extract and Loperamide on Gastrointestinal Altering Motor Function. J Med Food 2019; 22:1235-1245. [DOI: 10.1089/jmf.2019.0051] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Affiliation(s)
- Saber Jedidi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
- Laboratory of Sylvo-Pastoral Resources, University of Jendouba, Sylvo-Pastoral Institute of Tabarka, Tabarka, Tunisie
- Faculty of Sciences of Bizerte, University of Carthage, Zarzouna, Tunisia
| | - Kais Rtibi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
| | - Slimen Selmi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
| | - Foued Aloui
- Laboratory of Sylvo-Pastoral Resources, University of Jendouba, Sylvo-Pastoral Institute of Tabarka, Tabarka, Tunisie
| | - Houcine Selmi
- Laboratory of Sylvo-Pastoral Resources, University of Jendouba, Sylvo-Pastoral Institute of Tabarka, Tabarka, Tunisie
| | - Dalanda Wannes
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
| | - Houcem Sammari
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
| | - Nourhène Dhawefi
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
| | - Abbes Chaâbane
- Laboratory of Sylvo-Pastoral Resources, University of Jendouba, Sylvo-Pastoral Institute of Tabarka, Tabarka, Tunisie
| | - Hichem Sebai
- Unit of Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Higher Institute of Biotechnology of Beja, Beja, Tunisia
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Silveira ES, Bezerra SB, Ávila KS, Rocha TM, Pinheiro RG, de Queiroz MGR, Magalhães PJC, Santos FA, Leal LKAM. Gastrointestinal effects of standardized Brazilian phytomedicine (Arthur de Carvalho Drops®) containing Matricaria recutita, Gentiana lutea and Foeniculum vulgare. PATHOPHYSIOLOGY 2019; 26:349-359. [PMID: 31668916 DOI: 10.1016/j.pathophys.2019.09.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 08/22/2019] [Accepted: 09/06/2019] [Indexed: 12/13/2022] Open
Abstract
Arthur de Carvalho Drops® (ACD) is a traditional Brazilian herbal medicine used to treat functional gastrointestinal disorders (FGIDs). ACD is a formulation of herbal extracts from Matricaria recutita (chamomile), Foeniculum vulgare (fennel) and Gentiana lutea L. (gentian). Considering the popular use for FGIDs, the aim of this work was to investigate the ACD effect on gastric and intestinal parameters with emphasis in a mechanistic approach using isolated duodenal preparations of rodents. Analytical method was developed and validated for quantify three actives principles/markers (Apigenin-7-glucoside, gentiopicroside and anethole) in ACD. The treatment with ACD significantly reduced the emetogenic stimuli induced by cisplatin in rats, showed a laxative effect, reduced the bethanechol-enhanced gastrointestinal transit and completely reversed the contraction induced by carbachol in rat duodenum. However, ACD did not alter the secretory gastric volume or total gastric acidity. The ACD affect the contractions of duodenal smooth muscle mediated by Ca2+ channels and it is also able to inhibit the contractile response mediated by the release from its intracellular store. Furthermore, the relaxant effects of ACD appear independent of the nitric oxide pathway in rat duodenum. These results suggest that ACD could be beneficial for the treatment of disorders of the gastrointestinal tract.
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Affiliation(s)
- Elizama S Silveira
- Centro de Estudos Farmacêuticos e Cosméticos (CEFAC), Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
| | - Suzana B Bezerra
- Centro de Estudos Farmacêuticos e Cosméticos (CEFAC), Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
| | - Kalyane S Ávila
- Centro de Estudos Farmacêuticos e Cosméticos (CEFAC), Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
| | - Talita M Rocha
- Centro de Estudos Farmacêuticos e Cosméticos (CEFAC), Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil; Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
| | - Romelia G Pinheiro
- Centro de Estudos Farmacêuticos e Cosméticos (CEFAC), Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
| | - Maria Goretti R de Queiroz
- Centro de Estudos Farmacêuticos e Cosméticos (CEFAC), Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
| | - Pedro Jorge Caldas Magalhães
- Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
| | - Flávia Almeida Santos
- Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
| | - Luzia Kalyne A M Leal
- Centro de Estudos Farmacêuticos e Cosméticos (CEFAC), Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
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Antidiarrhoeal mechanism study of fulvic acids based on molecular weight fractionation. Fitoterapia 2019; 137:104270. [DOI: 10.1016/j.fitote.2019.104270] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 07/17/2019] [Accepted: 07/18/2019] [Indexed: 11/18/2022]
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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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Cavalcanti PMS, Martins MDOCC, Nunes PHM, Alves Filho FC, Silva JDP, Cavalcanti SMG. Antidiarrheal effect of extract from the bark of Combretum leprosum in mice. AN ACAD BRAS CIENC 2018; 91:e20170932. [PMID: 30569966 DOI: 10.1590/0001-3765201820170932] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 05/07/2018] [Indexed: 11/21/2022] Open
Abstract
This study investigated the effects of the ethanolic extract from the bark of Combretum leprosum (ECL) on intestinal transit and castor-oil induced diarrhea in mice. The oral administration of ECL (750 and 1000 mg/kg) slowed intestinal transit (ID50 of 455 mg/kg). The ECL (250-1000 mg/kg) reduced castor-oil induced diarrhea, in a time- and dose-dependent manner (p < 0.05). To determine if antidiarrheal effect of ECL involves α2-adrenergic or opioid receptor activation, the mice were pretreated with antagonists of these receptors, yohimbine or naloxone respectively. None of these drugs inhibited the antidiarrheal effect of ECL. To test if antidiarrheal effect of ECL is due to an antisecretory action, we realized the enteropooling assay on rats. The ECL increased bowel content and did not inhibit intestinal fluid secretion increase induced by misoprostol (100 µg/kg, s.c.). To determine if antimotility effect of ECL is due to a reduction on gastric motility, we realized the organ bath assay in the rat fundus stomach. Isotonic recordings show that the carbachol /KCl - induced contraction was not reversed by the addition of ECL. In conclusion, our results suggest that ECL contains antidiarrheal compounds and these compounds could induce a reduction of intestinal tract motility.
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Affiliation(s)
- Paulo M S Cavalcanti
- Departamento de Bioquímica e Farmacologia (setor SG8), Centro de Ciências da Saúde, Universidade Federal do Piauí, Avenida Universitária, s/n, Ininga, 64049-550 Teresina, PI, Brazil
| | - Maria DO Carmo C Martins
- Departamento de Biofísica e Fisiologia (setor SG8), Centro de Ciências da Saúde, Universidade Federal do Piauí, Avenida Universitária, s/n, Ininga, 64049-550 Teresina, PI, Brazil
| | - Paulo H M Nunes
- Departamento de Biofísica e Fisiologia (setor SG8), Centro de Ciências da Saúde, Universidade Federal do Piauí, Avenida Universitária, s/n, Ininga, 64049-550 Teresina, PI, Brazil
| | - Francisco C Alves Filho
- Departamento de Biofísica e Fisiologia (setor SG8), Centro de Ciências da Saúde, Universidade Federal do Piauí, Avenida Universitária, s/n, Ininga, 64049-550 Teresina, PI, Brazil
| | - Janyerson D P Silva
- Departamento de Biofísica e Fisiologia (setor SG8), Centro de Ciências da Saúde, Universidade Federal do Piauí, Avenida Universitária, s/n, Ininga, 64049-550 Teresina, PI, Brazil
| | - Suzana M G Cavalcanti
- Coordenação de Fisioterapia, Centro de Ciências da Saúde, Universidade Estadual do Piauí, Rua Olavo Bilac, 2335, Centro (Sul), 64001-280 Teresina, PI, Brazil
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Alonso-Castro AJ, Zapata-Morales JR, Arana-Argáez V, Torres-Romero JC, Ramírez-Villanueva E, Pérez-Medina SE, Ramírez-Morales MA, Juárez-Méndez MA, Infante-Barrios YP, Martínez-Gutiérrez F, Carranza-Álvarez C, Isiordia-Espinoza MA, Flores-Santos A. Pharmacological and toxicological study of a chemical-standardized ethanol extract of the branches and leaves from Eysenhardtia polystachya (Ortega) Sarg. (Fabaceae). JOURNAL OF ETHNOPHARMACOLOGY 2018; 224:314-322. [PMID: 29913299 DOI: 10.1016/j.jep.2018.06.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 05/21/2018] [Accepted: 06/14/2018] [Indexed: 06/08/2023]
Abstract
Eysenhardtia polystachya is used for the empirical treatment of cancer, infections, diarrhea, inflammation, and pain. This study identified, using GC-MS, the main chemical components in an ethanol extract of E. polystachya branches and leaves (EPE) and tested its cytotoxic, antimicrobial, anti-diarrheal, anti-inflammatory, and antinociceptive effects. The in vitro and in vivo toxicity of EPE was evaluated using the comet assay in human peripheral blood mononuclear cells (PBMC) and the acute toxicity test in mice, respectively. The cytotoxic and the antimicrobial effects were performed using the MTT assay and the minimum inhibitory concentration (MIC) test, respectively. The levels of pro-inflammatory mediators in LPS-stimulated macrophages were measured to evaluate the in vitro anti-inflammatory effects of EPE. The antidiarrheal (castor oil test, small intestine transit, and castor oil-induced enteropooling), and anti-inflammatory activities (TPA and carrageenan) of EPE were also performed. The antinociceptive actions of EPE were carried out with the following tests: acetic acid, formalin, and hot plate. The hypnotic and locomotor effects were analyzed using pentobarbital and a rotarod system, respectively. The main component in EPE was D-pinitol (26.93%). The antidiarrheal and antinociceptive effects of D-pinitol were also evaluated. EPE showed low in vitro toxicity (DNA damage in PBMC at concentrations higher than 200 µg/ml), and low in vivo toxicity (LD50 > 2000 mg/kg i.p. and p.o.). Furthermore, EPE lacked cytotoxic activity (IC50 > 300 µg/ml) on human cancer cells, but showed good antimicrobial effects in E. coli (MIC=1.56 µg/ml) and S. aureus (MIC = 0.78 µg/ml). In multi-drug resistant microorganisms, EPE showed MIC> 100 µg/ml. EPE exerted in vitro anti-inflammatory effects, mainly, by the decrease in the production of H2O2 (IC50 = 43.9 ± 3.8 µg/ml), and IL-6 (73.3 ± 6.9 µg/ml). EPE (ED50 =7.5 ± 0.9 mg/kg) and D-pinitol (ED50 = 0.1 ± 0.03 mg/kg) showed antidiarrheal activity, and antinociceptive effects in the acetic acid test with ED50 = 117 ± 14.5 mg/kg for EPE and 33 ± 3.2 mg/kg for D-pinitol. EPE showed also antinociceptive activity in the phase 2 of the formalin test (ED50 = 48.9 ± 3.9 mg/kg), without inducing hypnotic effects or altering the locomotor activity in mice. The results here presented corroborate the folk medicinal use of Eysenhardtia polystachya in the treatment of infections, diarrhea, inflammation, and pain. D-pinitol, the main metabolite of EPE, showed antinociceptive and antidiarrheal effects with similar potency compared to standard drugs.
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Affiliation(s)
- Angel Josabad Alonso-Castro
- Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Mexico.
| | - Juan Ramón Zapata-Morales
- Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Mexico
| | - Victor Arana-Argáez
- Facultad de Química, Universidad Autónoma de Yucatán, Mérida, Yucatán, Mexico
| | | | - Eyra Ramírez-Villanueva
- Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Mexico
| | - Sabino Eduardo Pérez-Medina
- Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Mexico
| | | | - Mario Alberto Juárez-Méndez
- Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Mexico
| | - Yessica Paola Infante-Barrios
- Unidad Académica Multidisciplinaria de la Zona Huasteca, Universidad Autónoma de San Luis Potosí, Ciudad Valles, San Luis Potosí, Mexico
| | | | - Candy Carranza-Álvarez
- Unidad Académica Multidisciplinaria de la Zona Huasteca, Universidad Autónoma de San Luis Potosí, Ciudad Valles, San Luis Potosí, Mexico.
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Bezerra FF, Lima GC, Sousa NAD, Sousa WMD, Costa LEC, Costa DSD, Barros FCN, Medeiros JVR, Freitas ALP. Antidiarrheal activity of a novel sulfated polysaccharide from the red seaweed Gracilaria cervicornis. JOURNAL OF ETHNOPHARMACOLOGY 2018; 224:27-35. [PMID: 29803569 DOI: 10.1016/j.jep.2018.05.033] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Accepted: 05/23/2018] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The use of marine seaweeds as a source of natural compounds with medicinal purposes is increasing in Western countries in the last decades, becoming an important alternative in the traditional medicine of many developing countries, where diarrhea still remains a severe public health problem, with high rates of mortality and morbidity. Sulfated polysaccharides (PLS) extracted from red seaweeds can exhibit therapeutic effects for the treatment of gastrointestinal disorders. Thus, the pharmacological properties of the PLS from Gracilaria cervicornis, an endemic seaweed found in the Brazilian northeast coast, was evaluated as an alternative natural medication for diarrhea. AIM OF THE STUDY This study aimed to evaluate the antidiarrheal activity of sulfated polysaccharides (PLS) extracted from the red seaweed G. cervicornis in Swiss mice pre-treated with castor oil or cholera toxin. MATERIALS AND METHODS The seaweed Gracilaria cervicornis was collected at Flecheiras beach (city of Trairí, State of Ceará, Brazil) and the PLS was obtained through enzymatic extraction and administered in mice (25-30 g) before diarrhea induction with castor oil or cholera toxin. For the evaluation of the total number of fecal output and diarrheal feces, the animals were placed in cages lined with adsorbent material. The evaluation of intestinal fluid accumulation (enteropooling) on castor oil-induced diarrhea in mice occurred by dissecting the small intestine and measuring its volume. The determination of Na+/K+-ATPase activity was measured in the small intestine supernatants by colorimetry, using commercial biochemistry kits. The gastrointestinal motility was evaluated utilizing an activated charcoal as a food tracer. The intestinal fluid secretion and chloride ion concentration were evaluated in intestinal closed loops in mice with cholera toxin-induced secretory diarrhea. The binding ability of PLS with GM1 and/or cholera toxin was evaluated by an Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS The G. cervicornis PLS showed antidiarrheal effects in both acute and secretory diarrhea, reducing the total number of fecal output, diarrheic stools, intestinal fluid accumulation, and increasing small intestine Na+/K+-ATPase activity on castor oil-induced diarrhea. However, the PLS did not affect gastrointestinal motility, indicating that this compound has a different action mechanism than loperamide. In secretory diarrhea, the PLS decreased intestinal fluid secretion and small intestine chloride excretion, binding with GM1 and/or cholera toxin and blocking their attachment to the enterocyte cell surface. CONCLUSIONS In conclusion, PLS has a significant antidiarrheal effect in acute and secretory diarrhea. Further investigation is needed towards its use as a natural medicine to treat diarrhea.
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Affiliation(s)
- Francisco Felipe Bezerra
- Laboratory of Proteins and Carbohydrates of Marine Algae, Department of Biochemistry and Molecular Biology - Federal University of Ceará. Fortaleza, Ceará, Brazil
| | - Glauber Cruz Lima
- Laboratory of Proteins and Carbohydrates of Marine Algae, Department of Biochemistry and Molecular Biology - Federal University of Ceará. Fortaleza, Ceará, Brazil.
| | - Nayara Alves de Sousa
- Biotechnology and Biodiversity Center Research, BIOTEC, Post-graduation program in Biotechnology - Federal University of Piauí. Parnaíba, Piauí, Brazil
| | - Willer Malta de Sousa
- Laboratory of Proteins and Carbohydrates of Marine Algae, Department of Biochemistry and Molecular Biology - Federal University of Ceará. Fortaleza, Ceará, Brazil
| | - Luís Eduardo Castanheira Costa
- Laboratory of Proteins and Carbohydrates of Marine Algae, Department of Biochemistry and Molecular Biology - Federal University of Ceará. Fortaleza, Ceará, Brazil
| | - Douglas Soares da Costa
- Biotechnology and Biodiversity Center Research, BIOTEC, Post-graduation program in Biotechnology - Federal University of Piauí. Parnaíba, Piauí, Brazil
| | - Francisco Clark Nogueira Barros
- Laboratory of Proteins and Carbohydrates of Marine Algae, Department of Biochemistry and Molecular Biology - Federal University of Ceará. Fortaleza, Ceará, Brazil; Federal Institute of Education, Science and Technology of Ceará - Juazeiro do Norte, Ceará, Brazil
| | - Jand Venes Rolim Medeiros
- Biotechnology and Biodiversity Center Research, BIOTEC, Post-graduation program in Biotechnology - Federal University of Piauí. Parnaíba, Piauí, Brazil
| | - Ana Lúcia Ponte Freitas
- Laboratory of Proteins and Carbohydrates of Marine Algae, Department of Biochemistry and Molecular Biology - Federal University of Ceará. Fortaleza, Ceará, Brazil
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Rojas-Bedolla EI, Gutiérrez-Pérez JL, Arenas-López MI, González-Chávez MM, Zapata-Morales JR, Mendoza-Macías CL, Carranza-Álvarez C, Maldonado-Miranda JJ, Deveze-Álvarez MA, Alonso-Castro AJ. Chemical characterization, pharmacological effects, and toxicity of an ethanol extract of Celtis pallida Torr. (Cannabaceae) aerial parts. JOURNAL OF ETHNOPHARMACOLOGY 2018; 219:126-132. [PMID: 29545209 DOI: 10.1016/j.jep.2018.03.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 02/03/2018] [Accepted: 03/09/2018] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Celtis pallida Torr (Cannabaceae) is employed as a folk medicine for the treatment of inflammation, pain, skin infections, and diarrhea, among other diseases. AIM OF THE STUDY The purpose of this work was to assess the chemical composition, the in vitro and in vivo toxicity, the antimicrobial, anti-inflammatory, antidiarrheal, antinociceptive, locomotor, and sedative effects of an ethanolic extract obtained from Celtis pallida aerial parts (CPE). MATERIALS AND METHODS The composition of CPE was carried out by GC-MS. The in vitro and in vivo toxic activity of CPE was estimated with the comet assay (10-1000 µg/ml) for 5 h in peripheral blood mononuclear cells, and the acute toxicity test (500-5000 mg/kg p.o.), for 14 days, respectively. The antimicrobial effect of CPE was evaluated using the minimum inhibitory concentration (MIC) assay, whereas the antidiarrheal activity (10-200 mg/kg p.o.) was calculated using the castor oil test. The antinociceptive effects of CPE (50-200 mg/kg p.o.) were estimated with the acetic acid and formalin tests, as well as the hot plate test. The sedative and locomotor activities of CPE (50-200 mg/kg p.o.) were assessed with the pentobarbital-induced sleeping time test and the rotarod test, respectively. RESULTS The main compound found in CPE was the triterpene ursolic acid (22% of the extract). CPE at concentrations of 100 µg/ml or higher induced genotoxicity in vitro and showed low in vivo toxicity (LD50 > 5000 mg/kg p.o.). Additionally, CPE lacked (MIC > 400 µg/ml) antimicrobial activity but exerts antinociceptive (ED50 = 12.5 ± 1.5 mg/kg) and antidiarrheal effects (ED50 = 2.8 mg/kg), without inducing sedative effects or altering the locomotor activity. The antinociceptive activity of CPE suggests the participation of adrenoceptors, as well as the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway. CONCLUSION C. pallida exerts its antinociceptive effects probably mediated by the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.
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Affiliation(s)
- Edgar Isaac Rojas-Bedolla
- Department of Pharmacy, Division of Natural and Exact Sciences, University Guanajuato, Noria Alta sin número, C.P. 36040 Guanajuato, Gto., Mexico
| | - Jorge Luis Gutiérrez-Pérez
- Department of Pharmacy, Division of Natural and Exact Sciences, University Guanajuato, Noria Alta sin número, C.P. 36040 Guanajuato, Gto., Mexico
| | - Mario Iván Arenas-López
- Department of Pharmacy, Division of Natural and Exact Sciences, University Guanajuato, Noria Alta sin número, C.P. 36040 Guanajuato, Gto., Mexico
| | | | - Juan Ramón Zapata-Morales
- Department of Pharmacy, Division of Natural and Exact Sciences, University Guanajuato, Noria Alta sin número, C.P. 36040 Guanajuato, Gto., Mexico
| | - Claudia Leticia Mendoza-Macías
- Department of Pharmacy, Division of Natural and Exact Sciences, University Guanajuato, Noria Alta sin número, C.P. 36040 Guanajuato, Gto., Mexico
| | - Candy Carranza-Álvarez
- Multidisciplinary Academic Unit, Huastec Region, Autonomous University of San Luis Potosí, Ciudad Valles, San Luis Potosí, Mexico
| | - Juan José Maldonado-Miranda
- Multidisciplinary Academic Unit, Huastec Region, Autonomous University of San Luis Potosí, Ciudad Valles, San Luis Potosí, Mexico
| | - Martha Alicia Deveze-Álvarez
- Department of Pharmacy, Division of Natural and Exact Sciences, University Guanajuato, Noria Alta sin número, C.P. 36040 Guanajuato, Gto., Mexico
| | - Angel Josabad Alonso-Castro
- Department of Pharmacy, Division of Natural and Exact Sciences, University Guanajuato, Noria Alta sin número, C.P. 36040 Guanajuato, Gto., Mexico.
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Antidiarrheal Activity of 80% Methanolic Leaf Extract of Justicia schimperiana. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018. [PMID: 29541140 PMCID: PMC5818970 DOI: 10.1155/2018/3037120] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background Diarrhea is one of the leading causes of preventable death in developing countries and mainly affects children and infants. It has been reported that the leaf of Justicia schimperiana is used as an antidiarrheal agent in Libo Kemekem district, northwest Ethiopia. Method The 80% methanolic leaf extract of J. schimperiana was evaluated for its activity against castor oil-induced diarrhea, enteropooling, and gastrointestinal motility in mice. Results Significant reduction (p < 0.001) in the total defecation and diarrheal drops was produced by all the test doses of the extract. Percentage inhibition of wet feces was 42.58, 65.07, and 74.96% at 100, 200, and 400 mg/kg doses of the extract, respectively. The extract also significantly inhibited castor oil-induced enteropooling at all test doses. The percent reduction in mean weight of intestinal contents was 66.96, 67.83, and 76.52% at 100, 200, and 400 mg/kg doses of the extract, respectively. The extract significantly reduced gastrointestinal movement of charcoal meal as well at 200 (p < 0.01) and 400 mg/kg (p < 0.001) doses. Conclusion In conclusion, the methanolic leaf extract of J. schimperiana has an antidiarrheal activity and this supports the use of this plant in the treatment of diarrhea in the traditional settings.
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Hossain MM, Kabir MSH, Dinar MAM, Arman MSI, Rahman MM, Hosen SMZ, Dash R, Uddin MMN. Antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice. J Basic Clin Physiol Pharmacol 2017; 28:483-492. [PMID: 28771432 DOI: 10.1515/jbcpp-2015-0165] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2015] [Accepted: 04/01/2017] [Indexed: 06/07/2023]
Abstract
BACKGROUND The objective of the study was to evaluate the antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice. METHODS In the present study, the dried leaves of P. imbricatum were subjected to extraction with ethanol, and then it was fractioned by chloroform and pet ether solvent. Antidiarrheal effects were tested by using castor oil-induced diarrhea, castor oil-induced enteropooling, and gastrointestinal transit test. Antinociceptive activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test. RESULTS The standard drug loperamide (5 mg/kg) showed significant (p<0.001) inhibitory activity against castor oil-induced diarrhea, in which all the examined treatments decreased the frequency of defecation and were found to possess an anti-castor oil-induced enteropooling effect in mice by reducing both weight and volume of intestinal content significantly, and reducing the propulsive movement in castor oil-induced gastrointestinal transit using charcoal meal in mice. The results showed that the ethanol extract of P. imbricatum leaves has significant dose-dependent antinociceptive activity, and among its two different fractions, the pet ether fraction significantly inhibited the abdominal writhing induced by acetic acid and the licking times in formalin test at both phases. CONCLUSIONS These findings suggest that the plant may be a potential source for the development of a new antinociceptive drug and slightly suitable for diarrhea, as it exhibited lower activity. Our observations resemble previously published data on P. imbricatum leaves.
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Alonso-Castro AJ, González-Chávez MM, Zapata-Morales JR, Verdinez-Portales AK, Sánchez-Recillas A, Ortiz-Andrade R, Isiordia-Espinoza M, Martínez-Gutiérrez F, Ramírez-Morales MA, Domínguez F, Juache-Flores ME, Martínez R. Antinociceptive Activity of Ent-Dihydrotucumanoic Acid Isolated from Gymnosperma glutinosum Spreng Less. Drug Dev Res 2017; 78:340-348. [PMID: 28736816 DOI: 10.1002/ddr.21397] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Accepted: 07/01/2017] [Indexed: 11/10/2022]
Abstract
Preclinical Research The diterpene ent-dihydrotumanoic acid (DTA) was among the compounds isolated from Gymnosperma glutinosum (Spreng) Less (Asteraceae). There are no reports regarding the pharmacological effects of DTA. Cytotoxicity against cancer cells (1-250 µM), and the antibacterial (50-1400 µM) activity of DTA were evaluated using the MTT assay, and the minimum inhibitory concentration test, respectively. The antidiarrheal (1-100 mg/kg p.o.) and anti-inflammatory (2 mg/ear) effects of DTA were evaluated using castor oil and 12-O-tetradecanoylphorbol-13-acetate, respectively. The antinociceptive and sedative effects of DTA (1-100 mg/kg p.o.) were evaluated using two models of chemically-induced nociception, and the pentobarbital-induced sleeping time test, respectively. The antinociceptive mechanism of DTA was evaluated using the acetic acid writhing test with inhibitors related to pain processing pathways. The effects of DTA (10-100 mg/kg p.o.) on locomotor activity were evaluated using the rotarod test. DTA lacked cytotoxic activity (IC50 > 100 µM) on cancer cells, possessed moderate antibacterial effects against B. subtillis (MIC= 175 µM), moderate antidiarrheal and anti-inflammatory effects, and minimal vasorelaxant effects. In the formalin test, DTA showed antinociceptive effects in both phases. In the acetic acid test, DTA showed antinociceptive activity (ED50 = 50.2 ± 5.6 mg/kg) with potency similar to that of naproxen (NPX; ED50 =33.7 ± 4.5 mg/kg) an effect blocked by naloxone implicating an opioid mechanism. DTA also exerted antidiarrheal activity and showed no sedative effects or changes in locomotor activity in mice. Drug Dev Res 78 : 340-348, 2017. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Angel Josabad Alonso-Castro
- Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Guanajuato, México
| | - Marco Martin González-Chávez
- Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, San Luis Potosí, México
| | - Juan Ramón Zapata-Morales
- Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Guanajuato, México
| | - Alexia Karina Verdinez-Portales
- Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Guanajuato, México
| | | | | | - Mario Isiordia-Espinoza
- Escuela de Odontología, Universidad Cuauhtémoc plantel San Luis Potosí, San Luis Potosí, San Luis Potosí, México
| | - Fidel Martínez-Gutiérrez
- Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, San Luis Potosí, México
| | - Marco Antonio Ramírez-Morales
- Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Guanajuato, México
| | - Fabiola Domínguez
- Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, México
| | | | - Roberto Martínez
- Departamento de Química Orgánica, Instituto de Química, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, México
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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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Sisay M, Engidawork E, Shibeshi W. Evaluation of the antidiarrheal activity of the leaf extracts of Myrtus communis Linn (Myrtaceae) in mice model. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 17:103. [PMID: 28183311 PMCID: PMC5301383 DOI: 10.1186/s12906-017-1625-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 02/06/2017] [Indexed: 12/26/2022]
Abstract
Background Myrtus communis L. has a folkloric repute for the management of diarrhea and dysentery in different parts of the world. However, the safety and efficacy of the leaf extract have not been scientifically validated in animal model. This study was, therefore, aimed to investigate the antidiarrheal effect of 80% methanol extract (80ME) and solvent fractions of the leaves of Myrtus communis L. in mice. Methods The antidiarrheal activity of the 80ME and solvent fractions was evaluated against castor oil induced diarrheal model, charcoal meal and enteropooling tests. For the 80%ME, the test groups received 100, 200 and 400 mg/kg of the extract. In case of fractions, the test groups received various doses of fractions (200, 300, 400 mg/kg and an additional dose of 800 mg/kg for the aqueous fraction (AF)), where as negative controls received the vehicle (10 ml/kg) and positive controls received loperamide (3 mg/kg). Results The 80ME at 200 mg/kg (p < 0.05) & 400 mg/kg (p < 0.01) as well as the chloroform fraction (CF) and methanol fraction (MF) at 400 mg/kg (p < 0.05) significantly delayed the onset of diarrhea. Besides, the 80ME (at all tested doses) and both of these fractions (at 300 & 400 mg/kg) significantly decreased the frequency and weight of fecal outputs. Results from the charcoal meal test revealed that the 80ME, at all doses, (p < 0.001) as well as the CF and MF at 300 mg/kg (p < 0.05) & 400 mg/kg (p < 0.001) produced a significant anti-motility effect. Similarly, in the entero-pooling test, the 80ME (at all tested doses) (p < 0.01) as well as the CF and MF (at 300 & 400 mg/kg, p < 0.05) produced a significant decline in the weight and volume of intestinal contents, whereas the AF revealed significant effect (p < 0.05) at dose of 800 mg/kg only. Conclusion The study demonstrated that the 80ME and solvent fractions contain bioactive constituents that have antidiarrheal activity. Therefore, this study provides a scientific support for the acclaimed traditional use of Myrtus communis L for the treatment of diarrheal diseases.
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Kinuthia DG, Muriithi AW, Mwangi PW. Freeze dried extracts of Bidens biternata (Lour.) Merr. and Sheriff. show significant antidiarrheal activity in in-vivo models of diarrhea. JOURNAL OF ETHNOPHARMACOLOGY 2016; 193:416-422. [PMID: 27664442 DOI: 10.1016/j.jep.2016.09.041] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 09/17/2016] [Accepted: 09/20/2016] [Indexed: 06/06/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE OF THE STUDY Diarrhea remains one of the main killers of children aged below five years. Traditional antidiarrheal remedies form a potentially viable source of novel low cost efficacious treatments in low resource settings. There is therefore a pressing need to scientifically evaluate these remedies. AIM OF THE STUDY This study aimed to investigate the in vivo and in vitro antidiarrheal activity of freeze dried Bidens biternata, a herb used in traditional Ayurvedic medicine in the management of diarrhea. MATERIALS AND METHODS In the castor oil test, twenty (20) adult Sprague-Dawley rats were randomized to a negative control (normal saline, n=5), a positive control (5mg/kg loperamide, n=5), and two test groups. The low dose test group received 200mg/kg Bidens biternata extract (n=5) while the high dose test group received 400mg/kg B. biternata extract (n=5). Castor oil (4ml/kg) was then administered to the animals one hour after administration of the respective treatments after which the total mass of fecal output excreted after four (4) hours was determined. In the charcoal meal test fifteen (15) Sprague Dawley rats were randomized to a control group (normal saline 5ml/kg orally, n=5), a positive control group (atropine sulfate 0.1mg/kg i.p., n=5) and a test group (400mg/kg B. biternata extract, n=5). Charcoal meal was then administered via oral gavage to each rat thirty (30) minutes after the administration of the various treatments. The distance covered by the charcoal meal from the pylorus was then determined after sacrifice of the animals thirty minutes after the meal. In the enteropooling test twenty (20) Sprague-Dawley rats were randomized to a control group (5% v/v ethanol in normal saline, n=5), a positive control group (5mg/kg loperamide, n=5) and a test group (400mg/kg B. biternata extract, n=5). For each group prostaglandin E2 (PGE2) (100μg/kg) was administered immediately after the treatments. The animals were then sacrificed half an hour later and the volume of the small intestine contents determined. The effects of different concentrations of B. biternata extract (0.5. 1.0, 2.0, 3.0 and 5.0mg/ml) on jejunal contraction were investigated and a dose-response curve constructed using the experimental data after which The ED50 dose was determined. The effect of tamsulosin (α1 adrenergic blocker), yohimbine (α2 adrenergic blocker), propranolol (β adrenergic blocker) and naloxone (μ opioid blocker) on the contractile activity of the extract were also investigated. The experimental data were expressed as mean±standard error of mean (SEM) and then analyzed using one-way ANOVA followed by Tukey's post hoc test in cases of significance (set at p<0.05). RESULTS The freeze dried extracts of B. biternata had significant antidiarrheal effects in the castor oil induced diarrhea model (p<0.01) with the highest activity being observed at the 400mg/kg dosage level (1.66±0.81g vs. 4.54±0.51g control, p=0.01). B. biternata extract had significant effects on intestinal motility in the charcoal meal test compared to the control group (43.61±4.42% vs. 60.54±3.33%: p<0.05). B. biternata extract had a significant effect on PGE2 induced enteropooling (3.06±0.07ml vs. 4.74±0.10ml; p<0.001). The freeze dried extracts of B. biternata had a significant negative effect on the contractility of the isolated rabbit jejunum (p<0.001). The effects of the extract were significantly attenuated by tamsulosin (53.94±4.20% vs. 80.57±4.09%; p<0.01) and naloxone (53.94±4.20% vs. 73.89±7.26%; p<0.05). Yohimbine (p>0.05) and propranolol (p>0.05) however did not have any significant effect on the contractile activity of the extract. CONCLUSIONS The freeze dried extract of B. biternata possess significant antidiarrheal activity in both in vitro and in vivo models which appears to be mediated by modulating both the intestinal motility as well as the secretory activity. The results of this study also validate its traditional use as an antidiarrheal remedy.
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Affiliation(s)
- Dennis Gacigi Kinuthia
- Department of Medical Physiology, School of Medicine, University of Nairobi, P.O. Box 30197-00100, Nairobi, Kenya.
| | - Anne W Muriithi
- Department of Medical Physiology, School of Medicine, University of Nairobi, P.O. Box 30197-00100, Nairobi, Kenya.
| | - Peter Waweru Mwangi
- Department of Medical Physiology, School of Medicine, University of Nairobi, P.O. Box 30197-00100, Nairobi, Kenya.
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Kabir MSH, Hossain MM, Kabir MI, Ahmad S, Chakrabarty N, Rahman MA, Rahman MM. Antioxidant, antidiarrheal, hypoglycemic and thrombolytic activities of organic and aqueous extracts of Hopea odorata leaves and in silico PASS prediction of its isolated compounds. Altern Ther Health Med 2016; 16:474. [PMID: 27871266 PMCID: PMC5117591 DOI: 10.1186/s12906-016-1461-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Accepted: 11/15/2016] [Indexed: 12/01/2022]
Abstract
Background Hopea Odorata, locally known as Telsur (Bangladesh), has some traditional uses as folk medicine. This study aims to investigate the antioxidant, antidiarrheal, hypoglycemic and thrombolytic activities of H. odorata leaf extracts as new therapeutic prospects predicting the activity of some of the isolated compounds of this plant. Methods Leaves of Hopea odorata was extracted with pure methanol (MEHO), ethanol (EEHO) and water (AEHO). The extract was tested for antioxidant activity by using reducing power and H2O2 scavenging assay. Antidiarrheal effects were assayed by three standard methods of bioassay: Castor oil-induced diarrhea, Castor oil induced enteropooling and gastrointestinal transit test. Hypoglycemic effect was determined by normoglycemic model of mice. Thrombolytic activity was evaluated by clot lyses test for human and mice blood. In silico PASS prediction was applied for phytoconstituents namely Balanocarpol, Hopeaphenol and Ampelopsin H isolated from this plant. Result Among the all extracts, MEHO exhibited strong antioxidant activity in both reducing power and H2O2 scavenging assay. Phenol content of MEHO was 297.22 ± 0.78 mg/g and flavonol content was 91.53 ± 1.82 mg/g. All the experiment of extracts at dose of 200 and 400 mg/kg and the standard drug loperamide (5 mg/kg) showed significant (p < 0.001) inhibition against castor oil induced diarrhea and castor oil induced enteropooling in mice. There were also significant (p < 0.01) reduction in gastrointestinal motility in the charcoal meal test. Leaf extract showed no significant (P < 0.01) decrease of blood glucose compared to Glibenclamide in normoglycemic mice. Using an in vitro thrombolytic model, MEHO showed the highest and significant clot lysis of human and mice blood compared to Streptokinase. PASS predicted the wide range of antioxidant, free radical scavenger, Nitric oxide scavenger, cardioprotectant, hepatoprotectant, thrombolytic, fibrinolytic, antibacterial, antifungal, anticarcinogenic, anthelmintic and anti-inflammatory activity of examined phytoconstituents. Conclusion These findings suggest that the plant may be a potential source of new antidiarrheal, thrombolytic and antioxidative agents but it is found to have no antidiabetic capability. PASS prediction matched with present study for the extracts. Further study needs to identify the PASS predicted biological actions of the phytoconstituents. Electronic supplementary material The online version of this article (doi:10.1186/s12906-016-1461-x) contains supplementary material, which is available to authorized users.
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Role of gastrointestinal motility inhibition and antioxidant properties of myrtle berries (Myrtus communis L.) juice in diarrhea treatment. Biomed Pharmacother 2016; 84:1937-1944. [PMID: 27856110 DOI: 10.1016/j.biopha.2016.11.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 10/25/2016] [Accepted: 11/01/2016] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION The myrtle (Myrtus communis) belongs to the Myrtaceae family; it is one of the central plants as part of the list of medicinal plants in the Tunisian Pharmacopoeia. Myrtle berry was used for its astringent, tonic, and antiseptic properties, to treat diarrhea, hemorrhoids, and gastrointestinal injury. METHODS Adult male wistar rats were used to evaluate the normal gastro-intestinal transit and gastric emptying as well as castor oil-induced diarrhea, enteropooling tests, and small intestine oxidative stress. The effect of myrtle berries juice (MBJ) (5 and 10ml/kg, bw. p.o.) was after compared to the loperamide and clonidine effects. RESULTS MBJ significantly and dose-dependently inhibited the intestinal motility and gastric emptying. We also found that MBJ administration induced a significant dose-dependent protection against diarrhea and intestinal fluid accumulation. Castor oil-induced intestinal hypersecretion was accompanied by an oxidative stress status in the intestine, which was attenuated by MBJ administration. CONCLUSION We suggest that MBJ had a potent protective effects against castor oil-induced diarrhea in part due, to its antioxidant and antisecretory properties.
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Degu A, Engidawork E, Shibeshi W. Evaluation of the anti-diarrheal activity of the leaf extract of Croton macrostachyus Hocsht. ex Del. (Euphorbiaceae) in mice model. Altern Ther Health Med 2016; 16:379. [PMID: 27681095 PMCID: PMC5041311 DOI: 10.1186/s12906-016-1357-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Accepted: 09/09/2016] [Indexed: 03/03/2023]
Abstract
Background Traditional healers in Ethiopia use a wide range of medicinal plants with antidiarrheal properties. Among these, Croton macrostachyus is one such plant claimed to have an antidiarrheal activity in Ethiopian folklore medicine. Previous studies showed that the crude extract is endowed with the claimed property. The present study was undertaken to further the claim by screening different fractions for the said activity so that it could serve as a basis for subsequent studies. Methods The fractions were obtained by successive extraction in soxhlet apparatus with solvents of different polarity (chloroform & methanol) followed by cold maceration of the deposit of the methanol fraction with distilled water. The antidiarrheal activity was evaluated using castor oil induced diarrheal model, charcoal meal test and anti-enteropooling test in mice. The test groups received various doses (300, 400, 500 mg/kg and an additional dose of 1000 mg/kg for the aqueous fraction) of the fractions, whereas positive controls received either Loperamide (3 mg/kg) or Atropine (5 mg/kg) and negative controls received vehicle (10 ml/kg). Results In the castor oil induced model, the chloroform (at all test doses) and methanol (at 400 & 500 mg/kg) fractions significantly delayed diarrheal onset, decreased stool frequency and weight of feces. The aqueous fraction was however devoid of significant effect at all the tested doses. Chloroform and methanol fractions produced a significant dose dependent decline in the weight and volume of intestinal contents while the aqueous fraction did not have a significant effect. All the fractions produced a significant anti-motility effect either at all doses (chloroform fraction) or at middle and higher doses (methanol and aqueous fractions). Conclusion The present study demonstrated that the chloroform and methanol fractions possessed significant anti-diarrheal activity. Nevertheless, the aqueous fraction showed only significant anti-motility effect at the higher dose (1000 mg/kg) employed in the study.
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Mohammad SHK, Abul H, Tanvir AC, Mohammad MUR, Mohammed MH, Shabbir A. Study of antidiarrheal and anthelmintic activity methanol extract of Commelina benghalensis leaves. ACTA ACUST UNITED AC 2016. [DOI: 10.5897/ajpp2015.4434] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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Yacob T, Shibeshi W, Nedi T. Antidiarrheal activity of 80 % methanol extract of the aerial part of Ajuga remota Benth (Lamiaceae) in mice. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 16:303. [PMID: 27549408 PMCID: PMC4994251 DOI: 10.1186/s12906-016-1277-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Accepted: 08/10/2016] [Indexed: 11/10/2022]
Abstract
Background In the Ethiopian traditional medicine, the aerial part of Ajuga remota Benth is used in the treatment of diarrhea. There are different mechanisms by which Ajuga remota may have antidiarrheal effect. Some of the possible mechanisms are through its anthelmintic and antibacterial activity. The present study aimed to evaluate whether the antidiarrheal effect of the plant also include antimotility and antisecretory effect using 80 % methanol extract of A. remota (MEAR). Methods The MEAR was administered at doses of 200, 400, 600 and 800 mg/kg to four groups of mice (six animals per group) orally in castor oil diarrhea model. The effect of the extract on enteropooling and gastrointestinal transit model was also evaluated using the same grouping and dosing. Two other groups, one as control and the other as standard (loperamide 5 mg/kg) were used for comparison with the treatment groups. Results The extract at the doses of 400, 600, and 800 mg/kg produced a dose-dependent and significant inhibition both on the frequency and onset of diarrhea. The percentage purging frequency was 53.4, 66.7, 79.6, and 66.7 % (p < 0.001) at three doses of MEAR (400, 600, and 800 mg/kg) and with loperamide (5 mg/kg), respectively. The percentage inhibition in intestinal fluid accumulation was 42.5, 62.1, and 74.2 % (p < 0.001) at the doses of 400, 600 and 800 mg/kg of MEAR, respectively. The MEAR also inhibited the intestinal transit of charcoal meal in a dose dependent manner both in the normal and castor oil induced intestinal transit. Conclusion This study has shown that the 80 % methanol extract of A. remota contains pharmacologically active substances with significant antimotility and antisecretory effect contributing for its antidiarrheal activity.
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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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