Isolated Rabbit Jejunum Research Articles

Investigation on the gastrointestinal properties of ethanolic extract of Cannabis sativa through in vivo and in vitro approaches

Introduction: For thousands of years, Cannabis sativa has been used for its medical and recreational benefits. Nowadays, there is an increasing interest in the use of C. sativa and its non-psychoactive products/effects to treat certain diseases. This study was conducted to examine the gastrointestinal effects of a sequential ethanolic fraction of C. sativa threshing residues (EFCS). Methods: In vivo and in vitro approaches were used to investigate the gastrointestinal properties of EFCS. Antidiarrheal, antibacterial, spasmodic, laxative, and antiulcer effects were tested respectively against castor oil induced diarrhea, disc diffusion method, isolated tissue preparations, charcoal transit time, and ethanol induced ulcer model. Results: EFCS induced a spasmodic effect on an isolated rabbit jejunum, which was inhibited by atropine and verapamil. Moreover, under free calcium conditions, the effect of EFCS was significantly reduced. The acute toxicity assay in female and male mice showed that EFCS was a safe product. Additionally, EFCS like loperamide presented antidiarrheal effect in mice and inhibited intestinal fluid secretions. Unlike the standard drug (loperamide), EFCS increased the motility of the intestinal transit. Furthermore, EFCS showed a protective effect against gastric ulcers induced by ethanol in mice and exhibited antimicrobial properties against Bacillus cereus strains. Conclusion: The results of this study reveal that EFCS possesses anti-diarrheal, antibacterial, spasmodic, laxative, and anti-ulcer activities. EFCS has potential therapeutic use against gastrointestinal diseases. Also, our work values the non-psychoactive products of C. sativa.

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.

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 relevanceBerberis 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 studyTo 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 methodsLC 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. ResultsThe 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. ConclusionThe 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.

Pharmacological basis of bergapten in gastrointestinal diseases focusing on H+/K+ ATPase and voltage-gated calcium channel inhibition: A toxicological evaluation on vital organs.

Aim and objectives: This study aimed to establish a pharmacological basis for evaluating the effects of bergapten (5-methoxypsoralen) in gastrointestinal diseases and assessment of its toxicological profile. Methods: The pharmacokinetic profile was evaluated using the SwissADME tool. AUTODOCK and PyRx were used for evaluating the binding affinities. The obtained results were further investigated for a post-dock analysis using Discovery Studio Visualizer 2016. The Desmond software package was used to conduct molecular dynamic simulations of best bound poses. Bergapten was further investigated for antidiarrheal, anti-secretory, charcoal meal transit time, anti-ulcer, anti-H. pylori activity. Results: Bergapten at a dose of 50, 100, and 200mg/kg was proved effective in reducing diarrheal secretions, intestinal secretions, and distance moved by charcoal meal. Bergapten at the aforementioned doses acts as a gastroprotective agent in the ethanol-induced ulcer model that can be attributed to its effectiveness against H. pylori. Bergapten shows concentration-dependent relaxation of both spontaneous and K+ (80mM)-induced contractions in the isolated rabbit jejunum model; the Ca2+ concentration-response curves (CRCs) were shifted to the right showing potentiating effect similar to papaverine. For molecular investigation, the H+/K+ ATPase inhibitory assay indicated inhibition of the pump comparable to omeprazole. Oxidative stress markers GST, GSH, and catalase showed increased expression, whereas the expression of LPO (lipid peroxidation) was reduced. Histopathological examination indicated marked improvement in cellular morphology. ELISA and western blot confirmed the reduction in inflammatory mediator expression. RT-PCR reduced the mRNA expression level of H+/K+ ATPase, confirming inhibition of the pump. The toxicological profile of bergapten was evaluated by an acute toxicity assay and evaluated for behavioral analysis, and the vital organs were used to analyze biochemical, hematological, and histopathological examination. Conclusion: Bergapten at the tested doses proved to be an antioxidant, anti-inflammatory, anti-ulcer, and antidiarrheal agent and relatively safe in acute toxicity assay.

Anti-spasmodic and Gastroprotective Activities of Harungana madagascariensis Leaf: A Traditional Anti-diarrhoea Remedy

Pharmacognosy Research,2022,14,4,492-498.DOI:10.5530/pres.14.4.71Published:October 2022Type:Original ArticleAuthors:Adaobi C. Ezike, Nwoyi N. Bassey, Emenike C. Amah, Daniel U. Nwankpa, Aniebiet E. Samuel, and John O. Medewase Author(s) affiliations:Adaobi C. Ezike*, Nwoyi N. Bassey, Emenike C. Amah, Daniel U. Nwankpa, Aniebiet E. Samuel, John O. Medewase Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu, NIGERIA. Abstract:Background: Harungana madagascariensis Lam. ex Poir. (Hypericaceae) leaf extract is used by some communities in the Niger Delta to treat diarrhoea, ulcers, and wounds. Objectives: This study investigated the antispasmodic, antimotility and gastroprotective properties of methanol:dichloromethane (1:1) extract of H. madagascariensis leaves (HME). Materials and Methods: The antispasmodic activity was evaluated in vitro using actions on contractions of guinea pig ileum and rabbit jejunum provoked by spasmogens. The actions of HME on gastrointestinal transit was assessed in vivo using normal defaecation and charcoal meal transit time tests in rodents. The actions of HME on gastric ulcers produced by ethanol and indomethacin were investigated. The HME was also subjected to phytochemical analysis and acute toxicity tests. Results: The HME suppressed contractions of isolated rabbit jejunum and guinea pig ileum elicited by histamine and acetylcholine. The extract elicited significant (P<0.05) reduction of normal defaecation (12.50 - 100%) and gastrointestinal propulsion of charcoal meal in mice (17.60 - 43.08%). Additionally, the extract significantly (P<0.05) prevented both ethanol- and indomethacin-induced stomach ulcers. An oral LD50 >5000 mg/kg in mice was obtained by an acute toxicity assay on HME. Conclusion: The findings showed that the leaf of H. madagascariensis has gastroprotective, antispasmodic, and antimotility properties. Keywords:Charcoal meal test, Gastric lesions, Gastrointestinal motility, Guinea pig ileum, Rabbit jejunum, Tyrode solutionView:PDF (875.22 KB)

Anti-diarrhoeal effects of Garcinia kola (Heckel-Holl) seed methanolic extract and its fractions in animal models

This study investigated the In vitro spasmolytic and In vivo anti-diarrhoeal effects of Garcinia kola seed extract/fractions. Extraction was done by maceration in 70% methanol, serially partitioned in ethyl acetate and n-hexane. Qualitative phytochemical screening was carried out on the crude extract/fractions. The In vitro spasmolytic effect of the extract and fractions at different concentrations (0.5×103, 0.2×103,0.1×103, 0.6×102 mg/ml) were investigated against spontaneous and acetylcholine-induced contractions in isolated rabbit jejunum as well as histamine-induced contractions using isolated guinea pig ileum. The In vivo anti-diarrhoeal effect of the extract was evaluated using three diarrhoeal models: castor oil-induced diarrhoea, charcoal meal gastrointestinal transit time and castor oil-induced enteropooling. In each model, 25 mice were randomly divided into five groups of 5 mice each. Group I served as the untreated control, while group II was a positive control. Groups III-V were administered 125, 250 and 500 mg/kg of the crude methanol extract, respectively. The crude extract, ethyl acetate and aqueous fractions at 0.5×103 mg/ml respectively exhibited 14.4%, 12.9% and 12.2% spasmolytic activities against acetylcholine-induced rabbit jejunum contractions. Histamine-induced guinea pig ileum contractions were inhibited by crude extract (6.2%), ethyl acetate (6.2%), aqueous fraction (7.2%) at 0.6×102 mg/ml. For castor oil-induced diarrhoea, the crude extract at 500 mg/kg produced a significant (p &lt; 0.05) decrease in the diarrhoeal index and faecal weight with a percentage inhibition of 70.4% compared with controls. Similarly, the crude extract (500 mg/kg) significantly (p &lt; 0.05) decreased the charcoal meal gastrointestinal transit time with a percentage inhibition of 33.9% and elicited significant (p &lt; 0.05) intraluminal fluid reduction (9.1%) in castor oil-induced enter pooling test when compared with the untreated group. In conclusion, the anti-motility and anti-secretory activities of the crude extract were attributed to the phytochemical constituents present.

A-Effects of Drugs on Spontaneous Contractions of Rabbit Jejunum

Aim: To find out possible to determine effect of C. reflexa extract on spontaneous contractions of rabbit jejunum. Methods: Animal experimental in vitro study from 1st October 2017 to 30 September 2018 at Pharmacology experimental lab, Wah Medical College Wah Cantt. Study model was Isolated pieces of rabbit jejunum and ileum. Sampling Technique used was Simple Random. Tissue considered fit for experiment after initial equilibration and stabilization. Result: Three increasing concentrations (0.1mg/ml, 0.2mg/ml and 0.4mg/ml) of C. reflexa extract decreased the response to 3.83±0.40, 2.33±0.33 and 1.33± 0.21mm. Decrease in response was significant with p- value 0.04, 0.008 and 0.003 respectively. Conclusion: Freshly prepared aqueous solution of crude extract of C. reflexa decreases the amplitude of spontaneous contractions of isolated rabbit jejunum. Keywords: Rabbit jejunum, effect of drug

Dose-dependent Spasmolytic, Bronchodilator, and Hypotensive Activities of Panicum miliaceum L.

Panicum miliaceum L. is a medicinally effective plant used in indigenous system of medicine for a variety of ailments. However, there is no comprehensive study explaining its effectiveness in gastrointestinal tract, respiratory, and cardiovascular system ailments. This study was designed to validate the pharmacological basis for the folkloric use of Panicum miliaceum L. in diarrhea, asthma, and hypertension. Panicum miliaceum extract was analyzed to detect the presence of bioactive compounds by HPLC. The isolated rabbit jejunum, trachea, and aorta were used for in vitro experiments using tissue bath assembly coupled with Power Lab data acquisition system to explore their relative effects. In-vivo experiments were performed for anti-diarrheal activity. HPLC analysis revealed the presence of gallic acid, butylated hydroxytoluene, catechin, and quercetin. Concentration dependent activities were observed by relaxing K+ (low) induced contractions having spasmolytic effect with EC50 = .358 ± .052, bronchodilator (EC50 = 2.483 ± .05793), and vasorelaxant (EC50 = .383 ± .063), probably due to the ATP dependent potassium channel activation. It was confirmed through pre-exposure of glibenclamide (specific ATP-dependent K+ channel blocker) having similarities with cromakalim. Pm.Cr revealed its antidiarrheal via in vivo experiments on rats. This study indicates that Panicum miliaceum has antidiarrheal, spasmolytic, bronchodilator, and vasorelaxant activities probably due to the ATP dependent K+ channel activation.

Antidiarrheal and Antioxidant Activities of the Aerial Parts of Caralluma dalzielii N. E. Brown

Pharmacognosy Research,2022,14,1,82-88.DOI:10.5530/pres.14.1.12Published:December 2021Type:Original ArticleAuthors:Chinenye J. Ugwah-Oguejiofor, Halilu E. Mshelia, Junaidu Bello, Isah Inuwa, and Abdullahi Sulaiman Author(s) affiliations:Chinenye J. Ugwah- Oguejiofor1,*, Halilu E. Mshelia2,3, Junaidu Bello1, Isah Inuwa1, Abdullahi Sulaiman1 1Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences Usmanu Danfodiyo University Sokoto, Sokoto, NIGERIA. 2Department of Faculty of Pharmacy, Cyprus International University, Nicosia, Mersin 10, TURKEY. 3Department of Pharmacognosy and Ethnopharmacy, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, P.M.B. 2346 Sokoto, NIGERIA. Abstract:Background: Caralluma dalzielii N.E. Brown is commonly referred to as “Karan massalanci” in the Northwest Nigeria where it is used in treating several ailments including pain, diarrhea and stomach issues. Objectives: This study was aimed to investigate the antidiarrheal and antioxidant activities of aqueous aerial parts extract of Caralluma dalzielii. Materials and Methods: The aqueous aerial parts extract of Caralluma dalzielii (CDE) (100, 200 and 400 mg/kg) was evaluated for antidiarrheal properties against gastrointestinal motility, castor oil-induced and prostaglandin-E2 (PGE2) enteropooling models in Wistar rats. Its antioxidant properties were studied by determining the total phenolic content (TPC) using Folin-Ciocalteu reagent, its free radical scavenging activity using 1, 1-Diphenyl-2-Picrylhydrazyl (DPPH) and its ferric reducing antioxidant power (FRAP) assays using potassium ferrocyanide ferric chloride methods. Ascorbic acid was used as the reference. Spasmolytic effect was studied in isolated rabbit jejunum preparations in an organ bath experiment using acetylcholine (ACh). Results: CDE significantly (p<0.05) reduced gastrointestinal transit of charcoal meal and the total number of diarrheal feces in the animals. The total phenolic content was determined to be 36.67±3.33 mg GAE/g. IC50 value of 63.44 mg/mL was calculated in DPPH assay. The FRAP value was found to increase as the concentration of the extract increased. CDE inhibited acetylcholine-induced contraction of the rabbit jejunum in a concentration dependent manner with complete inhibition at 20.48 mg/mL of the extract. Conclusion: The extract of Caralluma dalzielii possesses antidiarrheal activities which may be related to its antimotility, antioxidant and antispasmodic properties. Keywords:Antioxidant, Antispasmodic, Caralluma dalzielii, Gastrointestinal motility, Rabbit jejunum.View:PDF (543.04 KB) Full Text

Argemone mexicana extract alleviates gastrointestinal disorders by stimulating muscarinic receptors and blocking voltage-gated L-type calcium channels

Objective: To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models. Methods: The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath. The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System. The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis, respectively. Results: The total phenolic and total flavonoids contents of the extract were (267.75 ± 5.77) mg GAE/g and (73.86 ± 6.01) mg QE/g, respectively. Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC50 value of 0.016 mg/ mL, which was blocked by atropine (0.3 μM). Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC50 value of 2.185 mg/mL. Furthermore, Argemone mexicana extract relaxed potassium (80 mM)-induced contractions (EC50: 9.07 mg/mL), similar to a standard drug verapamil. The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract (1-5 mg/mL) and verapamil (0.1-1 μM). In addition, the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks. Conclusions: Argemone mexicana shows cholinergic agonist and calcium channel blocker activities, as well as antiemetic effect. It may be used as a potential agent for treating gastrointestinal disorders.

Anti-ulcer property of methanol fraction of Callichilia subsessilis leaf extract in albino rats

Peptic ulcer is one of the major causes of morbidity and mortality worldwide. It is treated with herbal preparations in developing countries. This study investigated the anti-ulcer property of methanol fraction of Callichilia subsessilis leaf in albino rats. Methanol extract prepared through the cold maceration method was partitioned into chloroform and methanol fraction using a separating funnel. The methanol fraction of Callichilia subsessilis (MFCS) was concentrated in vacuo using a rotary evaporator. The acute toxicity was determined using the brine shrimp lethality test and the up-and-down method at a dose limit of 2000 mg/kg. The anti-ulcer activity of MFCS was evaluated at the doses of 12.5, 25 and 50 mg/kg using indomethacin-and ethanol-induced ulcer models. Misoprostol was used as a reference standard. The ulcer score, index and severity were determined using standard methods. Isolated rabbit jejunum tissue in Tyrode’s solution was used to establish the possible mechanism of anti-ulcer activity of MFCS. The LC50 and LD50 of MFCS were greater than 10,000 ppm and 2,000 mg/kg respectively. The MFCS exhibited significant (p &lt; 0.05) dose-dependent anti-ulcer activity in all the ulcer models used. The MFCS (25 mg/kg) produced 52% and 41.33% inhibition of ulcer index in the indomethacin- and ethanol-induced ulcer models respectively. In the isolated tissue model, MFCS caused significant (p &lt; 0.05) relaxation of the rhythmic contraction of the isolated rabbit jejunum and partially inhibited acetylcholine- and histamine-induced contraction of the jejunal smooth muscles. In conclusion, MFCS exhibited anti-ulcer (antihistaminic and anticholinergic) effects. This study justified the use of Callichilia subsessilis leaves in traditional medicine as an anti-ulcer remedy.

Underlying Mechanisms of Anti-spasmodic, Antidiarrheal, Antioxidant and Acute Toxicity Assessments of Aqueous Extract of Mentha Suaveolens Ehrh and its Fourier Transform Infra-red Spectroscopy Analysis

Objective: The aim of this present study is to investigate the antidiarrheal, spasmolytic and antioxidant activities of aqueous extract of Mentha suaveolens Ehrh (AEMS), to study their underlying mechanisms in animal models and to reveal its main functional groups using Fourier Transform Infra-Red Spectroscopy (FTIR).&#x0D; Methods: Mentha suaveolens Ehrh was studied for antidiarrheal activity on Wistar rats of both sexes at the doses of 200 and 800 mg/kg body weight using castor oil-induced diarrhea, castor oil-induced enteropooling and small intestinal transit models.&#x0D; The extract was studied for antispasmodic property in isolated rabbit jejunum using various spasmogenic agents including Ach (10-5M), KCl (100 mM) and in the absence and in the presence of L-NAME (10-4 M) and the methylene blue (10-5 M).The antioxidant capacity of AEMS was carried out using DPPH radical scavenging activity and the ferric reducing antioxidant potential (FRAP). Ascorbic acid and Butylated HydroxyToluene (BHT) were used as references. The functional chemical groups were determined by FTIR.&#x0D; Results: The great antidiarrheal potential of AEMS seems to be mediated through calcium antagonism. The marked and concentration-dependent induced spasmolytic effect of AEMS appears to involve Ca2+ voltage channel blockade and the NO/cGMP pathway activation. AEMS possessed strong and concentration-dependent antioxidant potency using DPPH and FRAP. Polyphenols, carboxyl and carbohydrates were found to be the main functional groups in the AEMS analyzed by FTIR.&#x0D; Conclusion: Overall, our current findings provide scientific proves in animal models for the traditional use of AEMS in folk medicine for the prevention or the treatment of gastrointestinal diseases in Morocco.

Effect of Aqueous Ethanol Stem Extract of Entada africana Guill. Et Perrott. on Castor Oil and Magnesium Sulphate-Induced Diarrhoea Models in Mice

This study investigated the phytochemical, elemental analysis, acute toxicity study of aqueous ethanol stem bark extract of Entada africana, as well as its antidiarrhoeal activity in mice and its effects on isolated rabbit jejunum. The preliminary phytochemical screening revealed the presence of alkaloids, flavonoids, cardiac glycosides, phenols, saponins, steroids, tannins and terpenoids. Elemental analysis of the extract showed the presence of magnesium (Mg), manganese (Mn), iron (Fe), copper (Cu), lead (Pb), zinc (Zn) and sodium (Na) while acute toxicity study revealed intraperitoneal median lethal dose (LD50) values for the extract to be 774.6 mg/kg body weight. The antidiarrheal effect of the extract was studied using castor-oil and magnesium sulphate induced diarrhoeal models (dropping test) and gastrointestinal transit test in mice. The result showed that the extract produced a dose-dependent protection against diarrhoea induced by castor oil and magnesium sulfate, with the highest protection (80 and 100%), obtained at 100 and 200 mg/kg. The extract significantly (p≤0.01) reduced the small intestinal transit of charcoal meal in mice at all doses tested. The extract (0.4-3.2 mg/ml) produced a concentration dependent relaxation of the rabbit jejunum, and the effects were blocked by propranolol (0.04 and 0.64 μg/ml). The results of this study showed that the extract contain pharmacologically active substance with antidiarrhoeal properties mediated through inhibition of hyper secretion and reduced gastrointestinal motility. These properties may explain the rationale for use of it’s stem bark as antidiarrhoeal remedy in traditional medicine.

Multiple Pathway-Mediated Gut-Modulatory Effects of Maerua subcordata (Gilg) DeWolf.

BackgroundGastrointestinal disorders are often poorly managed, especially in developing countries, where there are limited resources and therapeutic options. Despite the rich diversity of medicinal plants that offer effective treatment options with fewer side effects, studies that provide scientific verification are lacking. Maerua subcordata (Gilg) DeWolf is among the plants claimed to have wide traditional medicine, use, including as a remedy against gastrointestinal problems. Therefore, this work aimed to evaluate the gut-modulatory effects of a crude leaf extract of M. subcordata (MSL.Cr), as well as its possible mechanism of action.MethodsA castor oil (10 mL/kg)–induced diarrheal mouse model was used to evaluate the antidiarrheal effect of MSL.Cr, and the spasmodic/antispasmodic effect of the extract was assessed using isolated rabbit jejunum with and without addition of standard cholinergic agonists/antagonists to predict the possible mechanism of action.ResultsMSL.Cr exhibited 40% and 80% protection against castor oil–induced diarrhea in mice at doses of 500 and 1,000 mg/kg, respectively. In isolated rabbit jejunum, the extract increased spontaneous contractions at low doses (0.01–0.1 mg/mL), and was sensitive to atropine, whereas it showed complete inhibition at higher doses (0.3–1 mg/mL). It was shown that the relaxant effect was possibly mediated by the involvement of phosphodiesterase-enzyme inhibition and K+-channel activation. The extract potentiated the control concentration–response curve of carbachol, shifting it to the left, similarly to the control drug papaverine. The potassium-channel opening–like activity of MSL.Cr was possibly mediated by the involvement of aspecific K+-channels inhibition, since tetraethylammonium, anunselective antagonist of K+ channels, significantly reversed its inhibitory effect.ConclusionThis study showed that the M. subcordata leaf extract demonstrated gut-modulatory effects, possibly mediated by a combination of muscarinic-receptor stimulation, phosphodiesterase inhibition, and aspecific K+-channel activation.

Antiplatelet Aggregation, Cardiotonic, Anti-Inflammatory, Antioxidant, and Calcium Channel Antagonistic Potentials of Nepeta ruderalis Buch.

The objective of this study was to authenticate the ethnobotanical claims of the Nepeta ruderalis Buch.-Ham. (N. ruderalis) extract in the traditional system of medicine. Crude extract was prepared via a simple maceration process. DPPH free radical scavenging and carrageenan-induced rat paw edema models were used to monitor antioxidant and anti-inflammatory responses of the N. ruderalis extract. Furthermore, it was tested for antiplatelet aggregation, cardioprotective, and calcium channel antagonistic activities via standard documented protocols. The N. ruderalis extract exhibited 80.82% antioxidant activity (IC50 = 207.51 ± 4.36 μg) while the anti-inflammatory response was significant (p < 0.05 to p < 0.01) at 50 mg/kg (45.58%) and 100 mg/kg (60.90%) doses. Moreover, it was found to inhibit platelet aggregation (IC50 = 1.06 and 0.91 mg/mL) and, in addition, to increase the force of contraction at the concentration of 3.0-10 mg/mL with a decrease in the heart rate on isolated paired atria (EC50 = 11.78 mg/mL). Relaxant activity was observed on the isolated rabbit jejunum (EC50 = 0.96 mg/mL) and trachea (EC50 = 0.89 mg/mL). However, in a cumulative way, an 80-millimolar potassium-induced contraction was evaluated (EC50 = 1.31 mg/mL). The N. ruderalis extract exhibited antioxidant, anti-inflammatory, platelet aggregating, cardiotonic, and calcium channel antagonistic activities, therefore proving scientifically its effectiveness in the traditional system of medicine.

The antispasmodic effect of aqueous root bark extract of Carissa edulis (Forssk.) Vahl on isolated rabbit jejunum is mediated through blockade of calcium channels

The antispasmodic effect of aqueous root bark extract of Carissa edulis (Forssk.) Vahl on isolated rabbit jejunum is mediated through blockade of calcium channels

In Silico, Ex Vivo and In Vivo Studies of Roflumilast as a Potential Antidiarrheal and Antispasmodic agent: Inhibition of the PDE-4 Enzyme and Voltage-gated Ca++ ion Channels.

The aim of the present study was to evaluate the possible gut inhibitory role of the phosphodiesterase (PDE) inhibitor roflumilast. Increasing doses of roflumilast were tested against castor oil-induced diarrhea in mice, whereas the pharmacodynamics of the same effect was determined in isolated rabbit jejunum tissues. For in silico analysis, the identified PDE protein was docked with roflumilast and papaverine using the Autodock vina program from the PyRx virtual screening tool. Roflumilast protected against diarrhea significantly at 0.5 and 1.5 mg/kg doses, with 40% and 80% protection. Ex vivo findings from jejunum tissues show that roflumilast possesses an antispasmodic effect by inhibiting spontaneous contractions in a concentration-dependent manner. Roflumilast reversed carbachol (CCh, 1 µM)-mediated and potassium (K+, 80 mM)-mediated contractile responses with comparable efficacies but different potencies. The observed potency against K+ was significantly higher in comparison to CCh, similar to verapamil. Experiments were extended to further confirm the inhibitory effect on Ca++ channels. Interestingly, roflumilast deflected Ca++ concentration–response curves (CRCs) to the right with suppression of the maximum peak at both tested doses (0.001-0.003 mg/mL), similar to verapamil. The PDE-inhibitory effect was authenticated when pre-incubation of jejunum tissues with roflumilast (0.03-0.1 mg/mL) produced a leftward deflection of isoprenaline-mediated inhibitory CRCs and increased the tissue level of cAMP, similar to papaverine. This idea was further strengthened by molecular docking studies, where roflumilast exhibited a better binding affinity (-9.4 kcal/mol) with the PDE protein than the standard papaverine (-8.3 kcal/mol). In conclusion, inhibition of Ca++ channels and the PDE-4 enzyme explains the pharmacodynamics of the gut inhibitory effect of roflumilast.

Pharmacological and computational evaluation of Sapodilla and its constituents for therapeutic potential in hyperactive gastrointestinal disorders.

Objective(s):This study was designed to investigate various gastrointestinal effects of Manilkara zapota (Sapodilla), exploring its anti-diarrheal, anti-secretary, anti-spasmodic, anti-ulcer and anti-motility potential.Materials and Methods:Antidiarrheal and anti-secretary activities were investigated using castor oil induced diarrhea and castor oil induced fluid accumulation. Isolated rabbit jejunum tissues (antispasmodic) were employed for in vitro experiments. Antiulcer, antimotility and molecular docking were performed using ethanol-HCl induced ulcer assay, charcoal meal transit time and Auto Doc Vina.Results:Mz.Cr exhibited protection against castor oil-induced diarrhea (P<0.05 vs. saline group) and dose-dependently inhibited intestinal fluid secretions (P<0.001 vs. castor oil group). Mz.Cr caused relaxation of spontaneous and K+ (80 Mm)-induced contractions with EC50 values of 0.11mg/ml (0.08-0.1, n=4) and 0.16 mg/ml (0.09-0.2, n=4) respectively (*P<0.05**P<0.01 ***P<0.001). It showed protective effect against gastric ulcers induced by ethanol-HCl (P<0.001 vs. saline group). Mz.Cr reduced distance travelled by charcoal meal (P<0.001 vs. saline group). Plant constituents: caffeoylquinic acid and methyl 4-O-galloylchlorogenate showed high binding affinities (E-value≥-6.5 Kcal/mol) against histaminergic H2 receptors, H+/K+ ATPase pump and voltage gated L-type calcium channels, while possesses moderate affinities (E-value≥8 Kcal/mol) against histaminergic H1, muscarinic M1, M3 and mu-opioid, whereas lower affinities (E-value≥9.5 Kcal/mol) vs. calmodulin, adrenergic α1, phosphodiesterase enzyme and dopaminergic D2 receptors. Lupeol-3-acetate and β-amyrin-3-(3’-dimethyl) butyrate observed weak affinities.Conclusion:In present study, M. zapota is reported to exhibits anti-diarrheal, anti-secretory, anti-spasmodic, anti-motility, anti-ulcer effects and computational binding affinities against gastrointestinal targets.

Multiple Mechanisms of Flaxseed: Effectiveness in Inflammatory Bowel Disease.

Materials and Methods Aqueous-methanolic crude extracts of Flaxseed (Fs.Cr) and Flaxseed oil were tested against 6% acetic acid- (AA-) induced colitis in BALB/c mice. Microscopic damage parameters of the hematoxylin and eosin-stained and periodic acid-Schiff-alcian blue-stained sections of the colon were scored to be assessed. Possible antispasmodic mechanism was studied on isolated rabbit jejunum, while antibacterial activity was assessed in vitro for microbes implicated in IBD. Results In AA-induced colitis, Flaxseed oil was found to be more effective in reducing mortality and colonic ulcers than Fs.Cr at 500 mg/kg dose. Fs.Cr was more efficacious in increasing mucin content as compared to oil, exhibiting slightly greater anti-inflammatory effect (50% vs 35%) and reducing depth of lesion (55% vs 42.31%, respectively). Antispasmodic activity of Fs.Cr (0.03 and 0.1 mg/ml) was mediated by phosphodiesterase inhibitors (PDEI, possibly PDE-4 subtype) with a resultant increase in cAMP levels. Flaxseed oil PDEI activity was mild (1 and 3 mg/ml). Fs.Cr (0.1 and 0.3 mg/ml) was potent in exhibiting anticholinergic activity, similar to dicyclomine, whereas Flaxseed oil showed anticholinergic effect at 1 and 3 mg/ml. Flaxseed oil (9 and 14 µg/ml) was bactericidal against enteropathogenic E.coli (EPEC), enterotoxigenic E.coli (ETEC), and enteroaggregative E.coli (EAEC), whereas Fs.Cr exhibited bactericidal effect against EPEC at 100 µg/ml. Conclusions Results of this study, taken together with previous studies, suggest that Flaxseed possesses anti-inflammatory, antibacterial, and antispasmodic action through multiple pathways and thus offers promising potential to be developed for IBD.

Pharmacological Modulation of Smooth Muscles and Platelet Aggregation by Psidium cattleyanum.

Traditionally, in the Southern Asian countries, Psidium cattleyanum is a widely used plant for the management of various ailments such as gastrointestinal, respiratory, and cardiac disorders, but it lacks proof on a scientific basis, and therefore, this is the major emphasis of the current research work. Crude extract of Psidium cattleyanum (Pc.Cr) was preliminary analyzed for the presence of different classes of bioactive molecules. The aqueous and dichloromethane fractions of Pc.Cr were subjected to in vitro and in vivo studies. It was applied at variable concentrations (0.1–10 mg/ml) to isolated rabbit jejunum to investigate spasmolytic effect. Concentration dependent curves of calcium were constructed to check the calcium channel antagonistic activity. For the evaluation of tracheorelaxant activity, isolated tracheal tissue was treated with High-K+ (80 mM) and carbachol (CCh) and then challenged cumulatively with Pc.Cr. To study the antidiarrheal effect of the plant extract, castor oil-induced diarrhea model was adopted. For evaluation of the hypotensive effect of Pc.Cr, it was given intravenously to preanesthetized normotensive rats, and the response was recorded using pressure transducer. Platelet rich plasma was used for the assessment of the antiplatelet activity when challenged with purinergic and adrenergic agonists. Concentration-dependent inhibition of spontaneous and High-K+ mediated contractions in isolated jejunum was observed by the application of Pc.Cr. Contractions induced in isolated tracheal tissue by High-K+ and CCh were inhibited by application of Pc.Cr to these tissues. Similarly, application of Pc.Cr to High-K+ and phenylephrine (PE) treated aortic strips resulted in vasodilation. Platelet aggregation inhibition was shown by Pc.Cr against adenosine diphosphate (ADP) only. The antidiarrheal effect was observed as a reduction in the total number of feces in Pc.Cr-treated mice when given castor oil. Dose-dependent hypotension was seen in normotensive rats when treated with Pc.Cr intravenously. This study showed the spasmolytic, tracheorelaxant, vasodilator, platelet aggregation inhibitory, antidiarrheal, and hypotensive activities of P. cattleyanum which may be due to the blockage of calcium channels, but the involvement of any other pathway cannot be ignored.