Calcium Channel Inhibitory Effect of Marjoram (Origanum majorana L.): Its Medicinal Use in Diarrhea and Gut Hyperactivity.

BACKGROUND: The leaves of Origanum majorana (O. majorana) are traditionally renowned for treating diarrhea and gut spasms. This study was therefore planned to evaluate its methanolic extract. METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to identify the phytochemicals, and Swiss albino mice were used for an in vivo antidiarrheal assay. Isolated rat ileum was used as an ex vivo assay model to study the possible antispasmodic effect and its mechanism(s). RESULTS: The GC-MS analysis of O. majorana detected the presence of 21 compounds, of which alpha-terpineol was a major constituent. In the antidiarrheal experiment, O. majorana showed a substantial inhibitory effect on diarrheal episodes in mice at an oral dosage of 200 mg/kg, resulting in 40% protection. Furthermore, an oral dosage of 400 mg/kg provided even greater protection, with 80% effectiveness. Similarly, loperamide showed 100% protection at oral doses of 10 mg/kg. O. majorana caused complete inhibition of carbachol (CCh, 1 µM) and high K+ (80 mM)-evoked spasms in isolated ileal tissues by expressing significantly higher potency (p < 0.05) against high K+ compared to CCh, similar to verapamil, a Ca++ antagonist. The verapamil-like predominant Ca++ ion inhibitory action of O. majorana was further confirmed in the ileal tissues that were made Ca++-free by incubating the tissues in a physiological salt solution having ethylenediaminetetraacetic acid (EDTA) as a chelating agent. The preincubation of O. majorana at increasing concentrations (0.3 and 1 mg/mL) shifted towards the right of the CaCl2-mediated concentration-response curves (CRCs) with suppression of the maximum contraction. Similarly, verapamil also caused non-specific suppression of Ca++ CRCs towards the right, as expected. CONCLUSIONS: Thus, this study conducted an analysis to determine the chemical constituents of the leaf extract of O. majorana and provided a detailed mechanistic basis for the medicinal use of O. majorana in hyperactive gut motility disorders.

Hydroethanolic extract of Piliostigma thonningii leaves extenuates the severity of diarrhoea in female Wistar rats.

OBJECTIVES: Nigeria ranks second in the global prevalence of diarrhoea with most cases concentrated in the Northern-region of the country. This research explored the antidiarrhoeal efficacy of the hydroethanolic extract of Piliostigma thonningii leaves (HEPTL), locally used to manage diarrhoeal conditions in Kebbi State, Nigeria. METHODS: P. thonningii leaves were screened for their secondary metabolites and mineral constituents. Using 3 standard-diarrhoea models, female Wistar rats completely-randomised into six-groups of six animals each were utilised for probing the antidiarrhoeal activity of HEPTL. Animals in groups I and II served as the negative and positive controls, whereas the rats in groups III, IV and V respectively received 50, 100, and 200 mg/kg body weight-(bw) of HEPTL. RESULTS: Six secondary metabolites and eight minerals were found in the extract, with flavonoids and calcium being the most abundant while steroids and zinc were the least prevalent, respectively. High performance liquid chromatographic analysis revealed the presence of 19 bioactive substances. Furthermore, there was a significant (p<0.05) and dose-related reduction in diarrhoea onset, water content, and wet faeces count. Similarly, the amount of intestinal fluid and average distance traversed by the charcoal-meal were decreased dose-dependently by the HEPTL with a commensurate rise in the suppression of intestinal fluid accrual and peristalsis. Acetylcholinesterase, Na+/K+-ATPase, reduced glutathione, intestinal-alkaline phosphatase and protein levels increased significantly (p<0.05) whereas superoxide-dismutase, catalase, intestinal-nitric oxide and malondialdehyde levels all fell significantly (p<0.05). However, the level of intestinal glucose was not significantly altered. CONCLUSIONS: Overall, the HEPTL exhibited a profound effect in the alleviation of the severity of diarrhoea, notably at 200 mg/kg bw.

Antidiarrheal coumarins from Psydrax schimperianus (A. Rich.) Bridson roots.

ETHNOPHARMACOLOGICAL RELEVANCE: Psydrax schimperianus (A. Rich.) Bridson. roots are used for the treatment of diarrhea in West Arsi zone, Ethiopia. AIM OF THE STUDY: This study aimed to investigate the in vivo antidiarrheal activity of crude extract and coumarins isolated from the roots of Psydrax schimperianus to provide a pharmacological basis for its traditional use as an antidiarrheal agent in Ethiopia. MATERIALS AND METHODS: The crude root extract of P. schimperianus was tested in vivo for antidiarrheal efficacy in mice utilizing castor oil-induced diarrhea, gastrointestinal transit time, and enteropooling models at doses of 100, 200, and 400 mg/kg. Phytochemical investigation of the crude root extract led to the isolation of two coumarins, isoscopoletin, and scoparone. Isoscopoletin and scoparone were evaluated for antidiarrheal activity against castor oil-induced diarrhea model at 10 mg/kg and 20 mg/kg doses. RESULTS: The crude root extract of P. schimperianus, at doses of 100, 200, and 400 mg/kg, inhibited defecation by 37.5%, 46.2%, and 61.2%, respectively. At a dose of 20 mg/kg, scoparone and isoscopoletin reduced defecation by 61.2% and 66.6%, respectively. CONCLUSION: The study warrants further investigation of isoscopoletin and scoparone towards development as a novel treatment for diarrheal diseases.

Ethnopharmacological basis and pharmacodynamics prospectives for folkloric claims of Rosa webbiana wall. Ex. Royle in diarrhea and asthma via In vitro, In vivo and In silico techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa webbiana (Family: Rosaceae) is used by South Asian herbalists to treat gastrointestinal and respiratory disorders. AIM OF THE STUDY: This research aimed at multiple targets to verify R. webbiana for treating diarrhea and asthma. In vitro, in vivo, and in silico experiments were planned to demonstrate the antispasmodic and bronchodilator potential of R. webbiana. MATERIALS AND METHODS: The bioactive compounds of R. webbiana were identified and quantified through LC ESI-MS/MS and HPLC. These compounds were predicted for muti-mechanisms of bronchodilator and antispasmodic potential in network pharmacology and molecular docking. In vitro methods (isolated rabbit trachea, bladder, and jejunum tissues) confirmed these multi-mechanisms for antispasmodic and bronchodilator effects. Antiperistalsis, antidiarrheal, and antisecretory experiments were conducted in in-vivo experiments. RESULTS: The phytochemical analysis indicates the presence of rutin (742.91 µg/g), kaempferol (726.32 µg/g), and quercitrin (688.20 µg/g) in Rw. EtOH. These bioactive compounds in network pharmacology interfere with the pathogenic genes of diarrhea and asthma, which are the members of calcium-mediated signaling pathways and showed the stronger binding affinity towards voltage-gated L-type calcium channels, myosin light chain-kinase, Calcium calmodulin-dependent-kinase, Phosphodiesterase-4, and phosphoinositide phospholipase-C in molecular docking. Rw. EtOH elicited a spasmolytic response in isolated jejunum, trachea, and urine preparations by relaxing K+ (80 mM) and CCh (1 µM) spastic contractions. Additionally, it suppressed calcium concentration-response curves to the right, like verapamil. Like dicyclomine, it caused a rightward parallel shift of the CCh curves, followed by a non-parallel shift at higher concentrations with suppression of the maximal response. Like papaverine, it also caused isoprenaline-induced inhibitory CRCs to shift to the left. Verapamil did not potentiate isoprenaline-induced inhibitory CRCs, although it was more efficacious against K+ (80 mM) than CCh (1 µM)-induced contractions. R. webbiana EtOH extract exhibited complete antiperistalsis (21.55%), antidiarrheal (80.33%), and antisecretory (82.59±0.60) activities in vivo experiments at the dose of 300 mg/kg. CONCLUSION: Thus, Rw. EtOH modulated multiple pathways, produced calcium antagonistic, anticholinergic, and phosphodiesterase inhibitory actions, and had antidiarrheal and bronchodilator effects.

Antidiarrheal, antisecretory and intestinal smooth muscle relaxant effects of Platanus orientalis in mice.

Platanus orientalis is traditionally used to treat diarrhea and spasm. However, studies are lacking on its mechanism of action in diarrhea and spasm. Pharmacological in-vivo activities were performed. In-vitro activities were carried out to explore the underlying mechanism(s) of action in isolated tissue preparations of mice jejunum and ileum. Crude extract of Platanus orientalis, loperamide and verapamil were used. The crude extract provided dose-dependent protection in castor oil diarrhea like verapamil and reduced the intestinal fluid accumulation and charcoal meal transit distance. In-vitro studies produced spasmolytic effect on the spontaneous (EC50 value=0.21mg/mL), high K+ (EC50 value=0.37mg/mL) and carbachol (CCh)-induced contractions 5.35mg/mL (3.88-6.85) respectively. The quiescent ileum responded well to the high K+ and carbachol (CCh)-induced contractions when tested against crude extract. It caused inhibition of the induced contraction with EC50 values of 0.20mg/mL (0.10-0.30) and 3.25mg/mL (2-4.5) respectively and showed potent effect against CCh-induced contractions. Calcium response curves produced a similar effect to verapamil. The crude extract of Platanus orientalis remained safe up to 5g/kg dose.

Metabolomics integrated network pharmacology reveals the mechanism of Ma-Mu-Ran Antidiarrheal Capsules on acute enteritis mice.

Acute enteritis (AE) is a type of digestive disease caused by biochemical factors that irritate the intestinal tract or pathogenic bacteria that infect it. In China, Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) have been applied against diarrhea caused by AE and bacillary dysentery for many years, but the underlying mechanisms of their beneficial effects are not known. In the present study, network pharmacology and metabolomics were performed to clarify the active ingredients of MMRAC and explore the specific mechanism of MMRAC on AE mice. A total of 43 active components of MMRAC with 87 anti-AE target genes were identified, and these target genes were enriched in IL-17 and HIF-1 signaling pathways. Integration analysis revealed that purine metabolism was the critical metabolic pathway by which MMRAC exerted its therapeutic effect against AE. Specifically, MAPK14, MMP9, PTGS2, HIF1A, EGLN1, NOS2 were the pivotal targets of MMRAC for the treatment of AE, and Western blot analysis revealed MMRAC to decrease protein levels of these pro-inflammatory signaling molecules. According to molecular docking, these key targets have a strong affinity with the MMRAC compounds. Collectively, MMRAC relieved the colon inflammation of AE mice via regulating inflammatory signaling pathways to reduce hypoxia and improved energy metabolism.

Investigations of plausible pharmacodynamics supporting the antispasmodic, bronchodilator, and antidiarrheal activities of Berberis lycium Royle. Via in silico, in vitro, and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberis lycium Royle, a member of the Berberidaceae family, is a high-value medicinal plant with a documented history of usage in traditional medicine and has demonstrated significant therapeutic results among local populations throughout the globe. It is used traditionally in many parts of Pakistan to treat diarrhea, abdominal spasms, coughs, and chest problems. AIM OF THE STUDY: To investigate the antispasmodic, bronchodilator, and antidiarrheal effects of B. lycium and its possible underlying mechanisms through in silico, in vitro, and in vivo studies. MATERIALS AND METHODS: LC ESI-MS/MS analysis was used to identify bioactive components within the hydromethanolic extract of B. lycium. In silico studies, including network pharmacology and molecular docking, were utilized to investigate the antispasmodic and bronchodilator properties of the extract's bioactive components. In vitro pharmacological studies were conducted using isolated rabbit jejunum, trachea, urinary bladder, and rat ileum preparations. In vivo antidiarrheal activities were conducted in mice, including castor oil-induced diarrhea, intestinal transit, and castor oil-induced enteropooling. RESULTS: The LC ESI-MS/MS analysis of the hydromethanolic extract of B. lycium identified 38 bioactive compounds. Network pharmacology study demonstrated that the mechanism of BLR for the treatment of diarrhea might involve IL1B, TLR4, PIK3R1, TNF, PTPRC, IL2, PIK3CD, and ABCB1, whereas, for respiratory ailments, it may involve PIK3CG, TRPV1, STAT3, ICAM1, ACE, PTGER2, PTGS2, TNF, MMP9, NOS2, IL2, CCR5, HRH1, and VDR. Molecular docking research revealed that chlorogenic acid, epigallocatechin, isorhamnetin, quinic acid, gallic acid, camptothecin, formononetin-7-O-glucoside, velutin, caffeic acid, and (S)-luteanine exhibited a higher docking score than dicyclomine with validated proteins of smooth muscle contractions such as CACB2_HUMAN, ACM3_HUMAN, MYLK_HUMAN, and PLCG1_HUMAN. In vitro investigations demonstrated that Blr.Cr, Blr.EtOAc, and Blr.Aq relaxed spontaneously contracting jejunum preparations; carbachol (1 µM)-induced and K+ (80 mM)-induced jejunum, trachea, and urinary bladder contractions in a concentration-dependent manner, similar to dicyclomine. Moreover, Blr.Cr, Blr.EtOAc, and Blr.Aq exhibited a rightward shift in Ca+2 and carbachol cumulative response curves, similar to dicyclomine, demonstrating the coexistence of antimuscarinic and Ca+2 antagonistic mechanisms due to the presence of alkaloids and flavonoids. In vivo antidiarrheal activities showed that the hydromethanolic extract was significantly effective against castor oil-induced diarrhea and castor oil-induced enteropooling, similar to loperamide, and charcoal meal intestinal transit, similar to atropine, in mice at doses of 50, 100, and 200 mg/kg body weight, which supports its traditional use in diarrhea. CONCLUSION: The dual blocking mechanism of muscarinic receptors and Ca+2 channels behind the smooth muscle relaxing activity reveals the therapeutic relevance of B. lycium in diarrhea, abdominal spasms, coughs, and chest problems.

The Roots of Neorautanenia mitis (A. Rich) Verdcourt: Further Evidence of Its Antidiarrhoeal Activity.

Despite the current management options and therapeutics used in the treatment of diarrhoea, in Africa and Asia, diarrhoea remains a major concern, especially in children under the age of 5 years. Traditional knowledge of medicinal plants used in the management of diarrhoea symptoms can be explored for their efficacy. In Nigeria, the TMPs (Traditional Medicine Practitioners) have, over the years, employed medicinal plants in the management of diarrhoea symptoms. In our current and previous studies, we aimed at validating the effectiveness of Neorautanenia mitis in the management of diarrhoea as claimed by the TMPs. Out of the 20 compounds isolated from N. mitis, the compounds neodulin, pachyrrhizine, neotenone and dolineone were the most abundant, and in this study, neodulin showed a pronounced relaxation of the rhythmic contraction of the isolated rabbit jejunum in an organ bath in a concentration-dependent manner, with a complete relaxation at 60 µg/mL. Neotenone and dolineone showed a dose-dependent inhibition of defecation of 65.07%, and 50.01%, respectively, at 20 mg/kg in a castor-oil-induced diarrhoea model. This is a strong indication that compounds from N. mitis possess antidiarrhoeal properties, thereby giving credence to its traditional usage in diarrhoea therapy, and therefore validating its antidiarrhoeal activity and its being worthy of further investigation.

Correlation Between Different Antidiarrheal Treatments and Changes in Chemical Components of Allii Sativi Bulbus Before and After Steaming Treatment Based on Flora Sequencing and In Vitro Experiments.

We investigated the changes in the main active ingredients and pharmacodynamic differences in the therapeutic effect of garlic before and after steaming and the correlation between them. The main active ingredients in raw garlic products (RGPs) and steamed garlic products (SGPs) were determined by high-pressure liquid chromatography and ultraviolet spectroscopy. Acute rapid diarrhea (AD) and antibiotic-induced diarrhea (DD) models were established in rats, and each group was treated with RGP and SGP, respectively. The main chemical components of garlic changed before and after steaming. Garlicin and alliinase were only found in RGP, whereas only alliin was found in SGP. Both RGP and SGP contained garlic polysaccharides. For in vivo experiments on AD, the average rate of loose stools was 100.00 ± 0.00, 31.55 ± 11.76, and 19.14 ± 6.62 in the RGP high-dose and SGP high-dose treatment groups, respectively; in DD, the rates were 91.11 ± 14.40, 19.33 ± 3.63, and 30.56 ± 4.30, respectively (P < .01, treatment vs. model groups). In AD, the average grade of loose stools was 2.33 ± 0.52 and 1.83 ± 0.75 in the model and RGP high-dose treatment groups, respectively (P < .05); in DD, the values were 2.17 ± 0.41 in the model group and 1.67 ± 0.52 in the SGP high-dose treatment group (P < .05). RGP had a better therapeutic effect on AD, mainly related to the antibacterial effect of garlicin in RGP. SGP had a better therapeutic effect on DD, mainly related to the alliin and garlic polysaccharide in SGP. This study could provide evidence to support the clinical use of garlic.

Antidiarrheal activity of the extracts of Valeriana jatamansi Jones on castor oil-induced diarrhea mouse by regulating multiple signal pathways.

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-1ß 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.

Antidiarrheal effect of the ethanol extract from Scutellaria barbata and its effect on the contraction of jejunum smooth muscles.

Scutellaria barbata (S. barbata), a traditional herbal medicine used in southern China, possesses anti-inflammatory, antitumor, spasmolytic and expectorant effects. However, there are not many recent studies on its gastrointestinal effects. This study aimed to evaluate the antidiarrheal effect of the ethanol extract of S. barbata (SBE) and its effect on the isolated jejunum smooth muscle. METHODS: The antidiarrheal effect of SBE (doses: 125, 250 and 500 mg/kg) on castor oil-induced diarrhea was investigated in vivo. The effect of SBE (0.01-10 mg/mL) on spontaneous or acetylcholine chloride (ACh, 10µM)/KCl (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was examined in vitro. The possible spasmolytic mechanism of SBE (1 and 3mg/mL) was analyzed by accumulating CaCl2 in a Ca2+-free high-K+ (60mM) solution. RESULTS: SBE (125, 250 and 500mg/kg) could delay the initial semi-solid onset time of mice and also reduce the diarrhea index in vivo. Furthermore, SBE (0.01-10mg/mL) could alleviate the spontaneous or ACh/KCl-induced contraction in vitro. SBE (1 and 3mg/mL) also inhibited the contraction induced by CaCl2, and the concentration-response curves of CaCl2 moved downward and to the right, similar to those of verapamil (0.01 and 0.1µM). CONCLUSIONS: SBE exerts antidiarrheal and spasmolytic effects, which provides a pharmacological basis for its use in functional gastrointestinal disorders.

Antispasmodic activity of the ethanol extract of Citrullus lanatus seeds: Justifying ethnomedicinal use in Pakistan to treat asthma and diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus lanatus (Thunb.) belongs to the ground family, Cucurbitaceae, known for edible fruit. Besides nutritional benefits, the traditional herbal practitioners in Pakistan and India used their seeds to treat gastrointestinal, respiratory, and urinary disorders. In Northern Sudan, its seeds are often used as a laxative. Its root is laxative and emetic at a high dose. Its seeds are also used to treat bedwetting and urinary tract obstruction. AIM OF THE STUDY: This study aimed to elucidate the multi-target mechanisms of Citrullus lanatus seeds to treat asthma and diarrhea. The pharmacological experiments were designed and conducted, along with the pharmacology network and molecular docking predictions, to verify the seeds biopotency for antispasmodic and bronchodilator properties. METHODS: LC ESI-MS/MS were performed to identify the potentially active compounds in hydroethanolic extract of Citrullus lanatus seeds, then to quantify them by HPLC. The quantified bioactive compounds of Citrullus lanatus, i.e., stigmasterol, quinic acid, malic acid, epicatechin, caffeic acid, rutin, p-coumaric acid, quercetin, ferulic acid, scopoletin, apigenin, and kaempferol were subjected to in silico studies for molecular docking. The hydroethanolic extract of Citrullus lanatus seeds was examined on isolated rabbit tissue, i.e., jejunum, trachea, and urinary bladder. The antiperistalsis, antidiarrheal and antisecretory studies were also performed in animal models. RESULTS: In silico studies revealed that bioactive compounds of C. lanatus seeds interfere with asthma and diarrhea-associated target genes, which are a member of calcium mediate signaling, regulation of cytosolic calcium concentration, smooth muscle contraction, and inflammatory responses. It was also found that rutin, quercetin, kaempferol, and scopoletin were stronger binding to voltage-gated calcium channels, calcium/calmodulin-dependent protein kinase, myosin light chain kinase, and phosphoinositide phospholipase C, thus, exerting calcium channel blocker activity. The hydroethanolic extract of C. lanatus seeds exerted a concentration-dependent relaxant response for the spasmolytic response on isolated jejunum and trachea preparations and caused relaxation of spastic contraction of K+ (80 mM). Furthermore, it caused a non-parallel rightward shift with suppression of calcium concentration-response curves. In animal models, the Cl.EtOH showed antiperistalsis, antidiarrheal and antisecretory response. CONCLUSION: Thus, we confirm Citrullus lanatus seeds have some medicinal effects by regulating the contractile response through target proteins of calcium mediates signaling and can be a promising component in the medical treatment for asthma and diarrhea.

Evaluation of the antidiarrheal activity of 80% methanol extract and solvent fractions of the leaf of Bersama abyssinica fresen (Melianthaceae) in mice.

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.

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.

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.

Tratamento da diarreia crônica com o medicamento homeopatico phosphorus: relato de caso / Treatment of chronic diarrhea with the homeopathic medicine phosphorus: case report

Há poucos estudos sobre a eficácia do tratamento homeopático na diarréia crônica, por isso relatos de casos são os primeiros degraus da evidência clínica [1]. As pesquisas utilizando medicamentos altamente diluídos têm avançado significativamente e a Medicina sempre está em busca de novas abordagens terapêuticas. Sendo a Homeopatia uma possibilidade no tratamento devido à sua alta resolutividade e baixo custo, comentamos sobre este tema que vem assumindo a cada dia mais importância na sociedade, devido aos impactos que provoca. Este relato de caso tem como objetivo principal apresentar o tratamento Unicista orientado por Hahnemann. Apresentamos o caso de uma paciente adulta que procurou consulta homeopática por diarréia crônica, após longo período de tratamento alopático sem resolução. Relatamos o atendimento, a repertorização e o tratamento com o medicamento policresto Phosphorus (simillimum da paciente). Demonstramos o surpreendente resultado obtido com o tratamento, respeitando a individualidade da paciente e observando os fundamentos da Homeopatia. Concluímos que a atuação do médico tem importância relevante na condução do tratamento e na melhora de qualidade de vida do seu paciente, e que a Homeopatia é uma grande aliada ao minimizar os danos deste transtorno. A cura de uma doença pode ser feita com tratamento homeopático Unicista segundo os ensinamentos do Pai da Homeopatia.

There are few studies on the effectiveness of homeopathic treatment in Chronic Diarrhea, so case reports are the first steps of clinical evidence. Researchs using highly diluted drugs has advanced significantly. Considering a challenge, Medicine is looking for new therapeutic approaches and Homeopathy is a possibility in the treatment due to its high resolution and low cost. We briefly comment on this topic, which is becoming increasingly important in society, due to the impacts it causes. This case report has as main objective to present the homeopathic treatment in a Unicist way according to the guidelines of Hahnemann. In the patient's search for homeopathy, we studied the case, performed the repertorization and found Phosphorus as the patient's simillimum. We demonstrate the surprising result obtained with the homeopathic treatment, respecting the patient's individuality and observing the fundamentals of Homeopathy. We conclude that the doctor's performance has relevant importance in the conduct of the treatment and in the improvement of the patient's quality of life, and that homeopathy is a great ally in minimizing the damage of this disorder. The cure of a disease can be done with Unicist homeopathic treatment according to the teachings of the Father of Homeopathy.

Anti-diarrheal therapeutic potential of diminazene aceturate stimulation of the ACE II/Ang-(1-7)/Mas receptor axis in mice: A trial study.

The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects on the body, especially on the cardiac system and gastrointestinal tract. ACE II is responsible for converting Ang II into the active peptide Ang-(1-7), which in turn binds to a metabotropic receptor, the Mas receptor (MasR). Recent studies have demonstrated that Diminazene Aceturate (DIZE), a trypanosomicide used in animals, activates the ACE II pathway. In this study, we aimed to evaluate the antidiarrheal effects promoted by the administration of DIZE to activate the ACE II/Ang-(1-7)/MasR axis in induced diarrhea mice models. The results show that activation of the ACE II pathway exerts antidiarrheal effects that reduce total diarrheal stools and enteropooling. In addition, it increases Na+/K+-ATPase activity and reduces gastrointestinal transit and thus inhibits contractions of intestinal smooth muscle; decreases transepithelial electrical resistance, epithelial permeability, PGE2-induced diarrhea, and proinflammatory cytokines; and increases anti-inflammatory cytokines. Enzyme-linked immunosorbent assay (ELISA) demonstrated that DIZE, when activating the ACE II/Ang-(1-7)/MasR axis, can still interact with GM1 receptors, which reduces cholera toxin-induced diarrhea. Therefore, activation of the ACE II/Ang-(1-7)/MasR axis can be an important pharmacological target for the treatment of diarrheal diseases.

Diagnosis and Treatment of Irritable Bowel Syndrome: A Review.

IMPORTANCE: The prevalence of irritable bowel syndrome (IBS) in the United States is between 7% and 16%, most common in women and young people, with annual direct costs estimated at more than $1 billion dollars in the United States. Traditionally, the diagnosis of IBS has been based on the positive identification of symptoms that correlate with several different syndromes associated with disorders such as IBS diarrhea, IBS constipation, functional diarrhea, functional constipation, chronic functional abdominal pain, or bloating. Several peripheral and central mechanisms initiate gastrointestinal motor and sensory dysfunctions leading to IBS symptoms. Those dysfunctions may require evaluation in patients whose symptoms do not respond to first-line treatments. OBSERVATIONS: Validation studies of consensus symptom-based criteria have identified deficiencies that favor a simpler identification of the predominant symptoms of abdominal pain, bowel dysfunction, and bloating and exclusion of alarm symptoms such as unintentional weight loss, rectal bleeding, or recent change in bowel function. Symptom-based diagnosis of IBS is enhanced with additional history for symptoms of somatoform and psychological disorders and alarm symptoms, physical examination including digital rectal examination, and screening tests to exclude organic disease (by measuring hemoglobin and C-reactive protein concentrations). The initial treatment plan should include patient education, reassurance, and first-line treatments such as fiber and osmotic laxatives for constipation, opioids for diarrhea, antispasmodics for pain and for management of associated psychological disorders. For patients who do not respond to those IBS treatments, testing for specific functional disorders may be required in a minority of patients with IBS. These disorders include rectal evacuation disorder, abnormal colonic transit, and bile acid diarrhea. Their identification is followed by individualized treatment, such as pelvic floor retraining for rectal evacuation disorders, sequestrants for bile acid diarrhea, and secretory agents for constipation, although there is only limited evidence that this individualized management approach is effective. CONCLUSIONS AND RELEVANCE: Advances in the identification of specific dysfunctions as causes of individual symptoms in the "IBS spectrum" leads to the potential to enhance the diagnosis and management of symptoms for the majority of patients for whom first-line therapies of IBS and management of comorbid psychological disorders are insufficient.

Lubeluzole: from anti-ischemic drug to preclinical antidiarrheal studies.

BACKGROUND: Lubeluzole, a neuroprotective anti-ischemic drug, was tested for its ability to act as both antibiotic chemosensitizing and antipropulsive agent for the treatment of infectious diarrhea. METHODS: In the present report, the effect of lubeluzole against antidiarrheal target was tested. The antimicrobial activity towards Gram-positive and Gram-negative bacteria was investigated together with its ability to affect ileum and colon contractility. RESULTS: Concerning the antimicrobial activity, lubeluzole showed synergistic effects when used in combination with minocycline against four common Gram-positive and Gram-negative bacteria (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922), although relatively high doses of lubeluzole were required. In ex vivo experiments on sections of gut smooth muscles, lubeluzole reduced the intestinal contractility in a dose-dependent manner, with greater effects observed on colon than on ileum, and being more potent than reference compounds otilonium bromide and loperamide. CONCLUSION: All above results identify lubeluzole as a possible starting compound for the development of a novel class of antibacterial adjuvants endowed with spasmolytic activity.

Chemotherapy-induced diarrhoea in dogs and its management with smectite: Results of a monocentric open-label randomized clinical trial.

Chemotherapy-induced diarrhoea (CID) is a frequent chemotherapy adverse event in dogs. Yet, there is currently no consensus regarding its management. Smectite is a natural medical clay, widely used in the treatment of acute diarrhoea in humans. The objectives of this study were to assess the efficacy of smectite in the management of CID in dogs, and to collect epidemiological data on CID. For each episode of diarrhoea, dogs were randomized into two management groups: Smectite group, receiving smectite at 0.5 g/kg PO per day divided in two to three doses initiated at the start of CID; control group, without initial medication. In both groups, rescue metronidazole was prescribed if CID progressed or was not improved within 48 hours. Sixty dogs were recruited and received 426 chemotherapy administrations between June 2017 and March 2019. The incidence rate of CID was 110/426 (25.8%, 95% CI: 21.7%-30.2%), and significantly differed between the chemotherapeutic drugs administered (P < .001). Metronidazole was administered in 5/54 events (9.3%, 95% CI: 3.1%-20.3%) in the smectite group and in 40/56 events (71.4%, 95% CI: 57.5%-82.3%) in the control group (P < .001). The time to resolution of diarrhoea was shorter (P < .001) in the smectite group (median: 19.5 hours, interquartile range [IQR]: 13.5-32 hours) compared with the control group (median: 53 hours, IQR: 31.5-113.5 hours). The results of this study support the administration of smectite in the first-line management of CID in dogs.

Investigation of ethnomedicinal use of Commiphora leptophloeos (Mart.) J. B. Gillett (Burseraceae) in treatment of diarrhea.

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.