Unraveling the multi-faceted role of Rosmarinus officinalis L. (rosemary) and diosmetin in managing gut motility.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosmarinus officinalis L. (Rosemary) is a popular herb with reported effectiveness against diarrhea, anxiety and constipation, albeit with limited pharmacological evidence. AIM OF THE STUDY: The current study was aimed at evaluating the therapeutic potential, possible pharmacological mechanisms of action and active constituents of hydro-ethanolic extract of rosemary (Rs.Cr), as potential anti-diarrheal, laxative and anxiolytic agent. METHOD: Rs.Cr was analyzed through reverse-phase high pressure liquid chromatography (RP-HPLC). Laxative, antidiarrheal, and anxiolytic activities were assessed using in vivo models. Spasmogenic and spasmolytic mechanisms were studied on isolated guinea pig ileum and rabbit jejunum tissues, respectively. Possible role of diosmetin, one of the active constituents of Rs.Cr was also evaluated. RESULTS: RP-HPLC analysis revealed presence of diosmetin, rutin and apigenin in Rs.Cr. Laxative effect was seen at low doses, which was partially reversed in atropinized mice. The spasmogenic mechanism was mediated by cholinergic and histaminergic receptors stimulation. At higher doses, antidiarrheal activity was evident, with reduction in gastrointestinal motility and secretions using charcoal meal and enteropooling assays, respectively. Rs.Cr also showed dose-dependent anxiolytic effect. The antispasmodic mechanisms were mediated by anti-muscarinic and K+ channel opening-like effect (predominant KATP-dependent). Diosmetin exhibited antidiarrheal and antispasmodic activities, but spasmogenic effect was not seen. CONCLUSION: Rosemary leaves have dual antidiarrheal and laxative effects, and as well as anxiolytic activity. In addition, the possible modulation of muscarinic and histaminergic receptors, and KATP channels show it as potential herb to be explored for irritable bowel syndrome. Diosmetin is possibly one of its constituents that contributes to its antidiarrheal activity.

Polyphenolic profile and ethno pharmacological activities of Callistemonsubulatus (Cheel) Craven leaves cultivated in Egypt.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Callistemon (syn. Melaleuca) of the myrtle family (Myrtaceae) has been documented as an integral part in the ethnobotanical system of the indigenous people of Australian mainland and many of its islands. Several Callistemons including the species subulatus were used by aboriginal Australians for making rafts, roofs for shelters, bandages, and food recipes, in addition to the management of wounds, infections, pain, cough, bronchitis, and gastrointestinal tract (GIT) disorders. AIM OF THE STUDY: The current study is designed to document the therapeutic effect of the aqueous methanolic extract (AME) of C. sabulatus Chell (syn. M. sabulata) leaves in the management of diarrhea and pain. Also, its influence on additional pharmacological modalities that are related to oxidative stress just as skin aging. Ultimately, the polyphenolic profile of the extract is disclosed and correlated to the aforementioned bioactivities. MATERIALS AND METHODS: The extract was fractionated using various chromatography techniques and the structures of the isolated compounds were determined based on their chemical and spectral data. The antioxidant activity was assessed using multiple models, including 2,2-diphenyl-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and ß-carotene bleaching assays. The anti-skin aging effect was evaluated using different relevant enzymatic assays. The antinociceptive activity was investigated using acetic acid-induced writhing, hot plate test, and formalin-induced paw licking in mice models. The antidiarrheal activity was gauge using the castor oil induced diarrhea, enter pooling and gastrointestinal motility in vivo models. RESULTS: Diverse polyphenols, including quercetin-3-O-ß-D-glucuronopyranoside (1), kaempferol-3-O-ß-D-glucuronopyranoside (2), strictinin (3), quercetin-3-O-(2``-O-galloyl)-ß-D-glucuronopyranoside (4), afzelin (5), di-galloyl glucose (6), mono-galloyl glucose (7), acacetin (8), apigenin-6,7-dimethyl ether (9), kaempferol trimethyl ether (10), dimethoxy chrysin (11), quercetin (12), kaempferol (13), methyl gallate (14), and gallic acid (15) were identified. The extract exhibited as significant antioxidant activity even better than that of Trolox or BHT. Moreover, it exerts elastase, tyrosinase, and collagenase inhibition activities, in addition to the significant peripheral and central analgesic activity in a dose-dependent manner (P < 0.0001). In castor oil induced diarrhea model, AME significantly prolonged the diarrhea onset, decreased the frequency of defecation, and weight of feces. Likewise, it exhibited a significant reduction in the gastrointestinal motility in charcoal meal model (P < 0.0001) and a considerable inhibitory effect on gastrointestinal transit and peristaltic index with all investigated doses (P < 0.0001). CONCLUSION: Ethnobotanicals are versatile resources for the management of various ailments by indigenous people and the experimental research is utmost to validate and uncover their pharmacological relevance. C. sabulatus leaves have strong antioxidant, analgesic, anti-skin aging, and antidiarrheal activities which are validated for the first time by various in vitro and in vivo models. The metabolic profile of the unprecedented AME of C. sabulatus leaves compromises a wide array of bioactive polyphenolic metabolites including, flavonoids, tannins, and phenolic acids that are correlated to the observed bioactivities. Altogether, ethnobotanicals with high and diverse contents of polyphenols are potential candidates for the management of various human aliments including neuropathies, GIT disorders, and skin aging conditions.

Effects of fermented ginseng on the gut microbiota and immunity of rats with antibiotic-associated diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng Meyer) is a well-known herb in traditional Chinese medicine and has been used to treat many diseases for thousands of years. Recent studies have shown that ginseng is a promising agent for improving the gut microbiota and treating ulcerative colitis. Fermentation is a common process in traditional Chinese medicine making that can be used to enhance efficacy and reduce toxicity. AIM OF THE STUDY: The purpose of the present study was to research the efficacy of ginseng fermented with probiotics (Lactobacillus fermentum) on the gut microbiota and immunity of rats with antibiotic-associated diarrhea (AAD). MATERIALS AND METHODS: SPF Sprague-Dawley rats were randomly divided into eight groups: control group, antibiotic group, natural recovery group, and five groups treated with different doses of fermented ginseng (FG1 to FG5). A model of AAD was established by treating the rats with triple antibiotics, and obvious symptoms of AAD were observed. A histopathological analysis of the colon was performed. The total bacteria in the intestinal microbiota and five types of gut microbes in the feces were detected by quantitative PCR. The expression levels of related immune factors TLR4 and NF-κB in the colon were assayed. RESULTS: An appropriate dose of fermented ginseng (0.5 g/kg/d) relieved some of the symptoms of AAD and colon inflammation and reduced the expression of the immune factors TLR4 and NF-κB in the colon. The alteration of the gut microbiota observed in the rats treated with antibiotics also returned to normal after treatment with fermented ginseng. Moreover, different doses of fermented ginseng exerted different influences on the gut microbiota, and excessively high or low doses of fermented ginseng were disadvantageous for resolving the symptoms of AAD and promoting recovery. CONCLUSIONS: These results demonstrate that fermented ginseng can treat AAD symptoms and colon inflammation and restore the gut microbiota to its original state.

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.

Effect of the leaves aqueous extract of Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) on intestinal function and its acute toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: In Argentine traditional medicine it is recorded the use of Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) leaves for treating various affections that compromise the intestinal normal functioning. AIM OF THE STUDY: The aim of this study was to assess the effect of J. rhombifolia leaves lyophilized aqueous extract on the intestinal function by means of in vivo and ex vivo experimental assays for determinate the antidiarrheal and antispasmodic capacity. Furthermore, was to evaluate its acute toxicity potential by oral and intraperitoneal administration of extract. MATERIALS AND METHODS: The in vivo assays were conducted by the experimental techniques of intestinal transit in mice, intestinal fluid accumulation in rats and Castor oil-induced diarrhea in mice. In the ex vivo assays, isolated rat duodenum and ileum segments were used for to evaluate the antispasmodic activity through contractile concentration-response curves induced by Carbachol and CaCl2. The acute toxicity of the extract was also investigated by oral and intraperitoneal administration. RESULTS: The extract intraperitoneal administration at the doses 125, 250 and 500 mg/kg, caused a marked reduction in the normal intestinal transit and in the number of diarrheal episodes in a dose-dependent manner. However, the extract did not produce significant changes in the intestinal fluid accumulation with any of the tested dose. The extract demonstrated a non-competitive inhibitory effect on the contractions of intestinal smooth muscle experimentally provoked by the spasmogenic agents Carbachol and CaCl2 in a dose-dependent manner (IC50 = 10.57 ± 1.38 and 6.29 ± 1.54 mg extract/ml Tyrode solution in the isolated organ bath, respectively). ANOVA indicated a significative effect of treatment (p < 0.001). CONCLUSIONS: The scientific evidence achieved based in the used experimental models allows us to indicate that J. rhombifolia leaves lyophilized aqueous extract manifest an antispasmodic activity on intestinal smooth muscle without observation of apparent toxicity symptoms.

Lythrum salicaria L. herb and gut microbiota of healthy post-weaning piglets. Focus on prebiotic properties and formation of postbiotic metabolites in ex vivo cultures.

ETHNOPHARMACOLOGICAL RELEVANCE: Herb of purple loosestrife (Lythrum salicaria L. from Lythraceae family) (LSH) was used in Europe since ancient times till early-20th century in the therapy of diarrhea and dysentery in human and veterinary medicine. Post-weaning diarrhea is a main problem affecting global piglet production, which leads to significant economic losses because of increased morbidity and mortality, reduced average daily gain, and high antibiotic consumption. Post-weaning diarrhea has various causes, all of which have been linked to imbalances of intestinal microbiota. The aim of the present study was to determine the interaction of LSH with the gut microbiota of healthy post-weaning piglets in order to evaluate its influence on microbiota composition and metabolism as well as production of potentially bioactive postbiotic metabolites from the extract constituents. MATERIALS AND METHODS: Ex vivo anaerobic cultures of piglets intestinal microbiota obtained from jejunum, ileum, caecum and distal colon were conducted in various culture media supplemented with LSH. The production of postbiotic metabolites was determined using UPLC-DAD-MSn method. Bacterial genomic DNA was extracted and examined by sequencing by amplification of the 16S rDNA V3-V4 hypervariable regions followed by bioinformatic analysis. The production of SCFA in cultures was determined by GC analysis. RESULTS: Only the caecal and distal colon microbiota was able to hydrolyze and metabolize ellagitannins present in LSH to urolithins. Urolithin M6, M7, urolithin C, A and iso-urolithin A were detected together with a previously not described metabolite originating from the flavogalloyl moiety of C-glucosylic ellagitannins. LSH had no significant influence on microbiota diversity and metabolic activity, but was able to modulate its composition by significant decrease in Collinsella, Senegalimassilia, uncultured bacteria belonging to Porphyromonadaceae, Rikenellaceae RC9 gut group, Mogibacterium, Dorea, Lachnoclostridium, Lachnospiraceae UCG-004 group, Moryella, [Eubacterium] coprostanoligenes, Intestinimonas, Ruminococcaceae UCG-005, uncultured bacteria belonging to Ruminococcaceae, Acidaminococcus and Allisonella, while the relative abundance of Prevotella, Agathobacter, [Eubacterium] hallii group, Lachnospiraceae NK3A20 group, [Ruminococcus] torques group, Catenibacterium, Catenisphaera and Megasphaera increased. Significant correlations between taxa abundance and production of urolithins were determined. CONCLUSIONS: In the present study we have shown, that Lythrum salicaria herb fulfills the criteria of a potential candidate for antidiarrheal agent, which could be applied as therapy or prevention of post-weaning diarrhea in piglets. It not only modulates the gut microbiota composition without causing the dysbiosis and impairing metabolic activity, but is also a source of postbiotic metabolites, namely urolithins, which anti-inflammatory properties can be beneficial for gut health of piglets during the weaning period.

Evaluation of carbon tetrachloride fraction of Actinodaphne angustifolia Nees (Lauraceae) leaf extract for antioxidant, cytotoxic, thrombolytic and antidiarrheal properties.

Actinodaphne angustifolia Nees (Family: Lauraceae) is commonly used in folk medicine against urinary disorder and diabetes. The objective of the present study was to evaluate the antioxidant, cytotoxic, thrombolytic, and antidiarrheal activities of carbon tetrachloride (CCl4) fraction of leaves of A. angustifolia (CTFAA) in different experimental models. Antioxidant activity was evaluated by using qualitative and quantitative assays, while antidiarrheal effects assessed with castor oil-induced diarrheal models in mice. The clot lysis and brine shrimp lethality bioassay were used to investigate the thrombolytic and cytotoxic activities, respectively. CTFAA showed antioxidant effects in all qualitative and quantitative procedures. The fraction produced dose-dependent and significant (P<0.05 and P<0.01) activities in castor oil-induced diarrheal models. Moreover, CTFAA significantly (P<0.05) demonstrated a 15.29% clot lysis effect in the thrombolytic test, and the brine shrimp lethality assay LC50 value was 424.16 µg/ml bioassay. In conclusion, the current study showed CTFAA has significant antidiarrheal effects along with modest antioxidant and thrombolytic effects, and these data warrant further experiment to justify and include CTFAA as a supplement to mitigate the onset of diarrheal and cardiovascular disease.

A flavonoid driven phyto-pharmacological effects of Capparis decidua Edgew. in rodents.

This study elicits the underlying mechanism(s) of Capparis decidua when used for different gut disorders. HPLC chromatogram of C. decidua extract (CD.Cr) and its respective fractions showed a variety of phytochemicals of which, kaempferol being in a high proportion. In mice, CD.Cr at doses of 70 and 150 mg/kg enhanced the wet feces output to 33 and 44% respectively as compared to carbachol (47.6%), while doses of 500 and 700 mg/kg, presented 41 and 70% safety against castor oil-driven diarrhea, respectively. Its flavonoid constituent, kaempferol at doses of (50 and 100 mg/kg) produced 51.7 and 82% safety when compared to nifedipine which provided 95% safety at dose of 40 mg/kg against castor oil-driven diarrhea like loperamide. In isolated jejunum preparations, C. decidua extract and its respective fractions (except pet-ether) produced atropine-sensitive inhibitory effects, whereas kaempferol and nifedipine showed atropine insensitive effects. Against high K+-induced contractions, C. decidua's fractions and kaempferol both exhibited a concentration-related non-specific inhibition while displacing the Ca++ -CRCs to right-ward with suppression in maximal response like nifedipine. In isolated rat ileal preparations, CD.Cr and respective fractions elicited atropine-sensitive gut excitatory responses. In summary, this article reports C. decidua's laxative effect through cholinergic receptor activation as well as its antidiarrheal effects, where its flavonoid constituent kaempferol produces Ca++ antagonist like activity, thus justifying C. decidua folk use in constipation and diarrhea.

Pharmacological investigation of activities pertaining to modulation of gastrointestinal, respiratory and cardiovascular parameters by Indigofera argentea in experimental models.

Indigofera argentea is widely used for the management of gastrointestinal, respiratory and cardiac disorders. This study was done to explore scientific basis of its uses. Aqueous methanolic extract of Indigofera argentea and its fractions were studied on isolated tissues of rabbit's jejunum, trachea, aorta and atrium. Castor oil induced diarrheal model was used for the study of the antidiarrheal effect and pre-anesthetized rats were used for hypotensive study. Concentration dependent spasmolytic effect of the extract upon isolated jejunum, trachea and aorta was observed. Concentration response curves constructed upon isolated rabbit jejunum, revealed the presence of calcium channel blocker in the plant extract. Moreover, significant reduction (P<0.05) in atrial force of contraction but non-significant reduction in rate of contraction was seen by the application of plant extract. Protection (P<0.05) against diarrhea was observed by the administration of crude extract to rats which were pretreated with castor oil. When given to rats intravenously, the extract showed hypotensive effect. Experimental findings justified the traditional uses of Indigofera argentea on pharmacological basis for the management of disorders pertaining to gut, airway and hypertensive situation.

Insight on the fractionations and structural characterizations of innovative antidiarrheal compounds screened from leaves of Psidium guajava of local origin in Pakistan.

Numerous ailments have been effectively treated with natural plants for long time all over the world. Plants provided a back bone for the exploration of novel medicinal compounds. Therefore, chief focus of our study was to isolate the biologically active compounds from the plant source and evaluate their antidiarrheal potentials, as diarrhea is still the most dominant disease in developing countries. The isolation and structure elucidation of two new compounds were identified from methanolic and chloroform extracts of Psidium guajava (guava) leaves. Extracts of plants were acquired by successive maceration from dried powder. Castor oil induced diarrheal-model was used to evaluate the antidiarrheal activity and therapeutic response was endorsed to the suppression of normal and wet stools in Spraug Dawley rats. Through the series of fractionations, compound-A was obtained from methanolic extract and named 3-(4-amino 1,3,8-tri-OH 5,6-di-CH3 7-propyl 1,2,3,4,4a,5,8,8a-octahydronaphthalen 2-yl) propanoic3-(4-NH3 7-butyl 1,3,8-tri-OH 5,6-di-CH3 1,2,3,4,4a,5,8,8a-octahydronaphthalen 2-yl)propanoic anhydride. Compound-B was entitled 5-(3-hydroxy-1,4-di-CH3-1,2,3,4,4a,5,8,8a-octahydronaphthalen-2-yl)pent-3-enoic acid was acquired from the chloroform extract. The structure elucidations of both compounds were interpreted through spectroscopic data, including EI-MS, FTIR, 1HNMR and 13C-NMR. The significant antidiarrheal activities were determined with crude extracts and isolated compounds. In inference, present study revealed that substantial antidiarrheal feature of guava is confined to the identified compounds.

Gastrointestinal and uterine smooth muscles relaxant and anti-inflammatory effects of corchorus olitorius leaf extract in laboratory animal models.

ETHNO-PHARMACOLOGICAL RELEVANCE: Corchorus olitorius is reportedly used in ethno-medicine to arrest threatened miscarriage and other conditions associated with excessive uterine contractions. The plant is also used as a purgative, demulscent and an anti-inflammatory agent. AIM OF THE STUDY: Against the background of ethno-medicinal use, this current work was designed to evaluate the gastrointestinal and uterine smooth muscles relaxant and anti-inflammatory effects of Corchorus olitorius leaf extract (COLE). MATERIALS AND METHODS: Pieces of uterine and gastrointestinal tissues were suspended separately in organ baths containing ideal physiological salt solutions bubbled with air and were tested for responses to standard drugs and COLE, then repeated in the presence of antagonists. Anti-inflammatory study was carried out via the egg albumin-induced paw edema model in rats. RESULTS: The application of COLE to pieces of uterine tissue significantly decreased the amplitudes of contractions in a dose dependent manner such that the highest dose applied (666.67 µg/ml) achieved a 100% inhibitory effect. Oxytocin induced contractions were also significantly inhibited by both salbutamol and COLE. On the isolated rabbit jejunum, the effect of COLE was also inhibitory and like atropine, significantly inhibited acetylcholine induced contractions. In the in vivo study, the extract inhibited charcoal meal movement in test rats when compared with control. Anti-inflammatory effect of COLE was significant and compared favourably with that of aspirin following in vivo trials. CONCLUSIONS: COLE therefore, may be a good tocolytic, anti-diarrheal and anti-inflammatory agent and offers hope of new drug discovery for such uses.

Evaluation of In Vivo Antidiarrheal Activities of Hydroalcoholic Leaf Extract of Dodonaea viscosa L.(Sapindaceae) in Swiss Albino Mice.

Traditionally people used Dodonaea viscosa for the treatment of various ailments, including diarrhea. Therefore, this study was aimed to evaluate the antidiarrheal activity of the 80% methanolic leaf extract of D viscosa against castor oil-induced diarrhea in mice models. Different doses of 80% methanolic leaf extract of D viscosa (100, 200, and 400 mg/kg) were evaluated for their antidiarrheal activities using castor oil-induced diarrhea, gastrointestinal transit, and enteropooling models in Swiss albino mice. At all test doses, the plant extract showed significant (P < .05) inhibition in the frequency of defecation of wet feces and total fecal output as compared to the control group. Similarly, at all dose ranges used the plant extract demonstrated significant (P < .05) reduction in an intraluminal fluid accumulation as compared to the untreated group. Besides, at higher doses, the plant extract also indicated significant (P < .05) antimotility activity in comparison with the control. In conclusion, these findings illustrated that the 80% methanolic leaf extract of D viscosa supported the traditional claim of antidiarrheal activity of the plant though further investigations are warranted.

Studies on antidiarrheal and laxative activities of aqueous-ethanol extract of Asphodelus tenuifolius and underlying mechanisms.

BACKGROUND: Asphodelus tenuifolius Cav. (Asphodelaceae) has traditional reputability in treatment of diarrhea and constipation but no scientific study has been reported for its gastrointestinal effects. Present study was conducted to evaluate antidiarrheal and laxative activities of the plant. METHODS: Aqueous-ethanol crude extract of Asphodelus tenuifolius (At.Cr) was subjected to phytochemical screening and liquid-liquid fractionation. In vivo studies of charcoal meal intestinal transit test, antidiarrheal activity against castor oil induced diarrhea and laxative activity were performed in mice. In vitro experiments were conducted upon rabbit jejunum preparations using standard tissue bath techniques. RESULTS: Phytochemical screening indicated presence of alkaloids, anthraquinones, flavonoids, saponins, steroids, tannins and phenols in At.Cr. In charcoal meal intestinal transit test, At.Cr increased (p < 0.001) intestinal motility at 100 mg/kg dose, but decreased (p < 0.001) it at 500 mg/kg dose, when compared to the control group. At.Cr (300-700 mg/kg) provided protection from castor oil induced diarrhea in mice, which was significant (p < 0.001) at 500 and 700 mg/kg doses, as compared to the saline treated control group. At.Cr (50 and 100 mg/kg) enhanced total and wet feces counts in normal mice, as compared to saline treated control. In jejunum preparations, At.Cr inhibited spontaneous, K+ (80 mM) and K+ (25 mM) mediated contractions, similar to verapamil. Pre-incubation of jejunum preparations with At.Cr resulted in rightward nonparallel shift in Ca+ 2 concentration response curves, similar to verapamil. The spasmolytic activity was concentrated in ethylacetate fraction. Aqueous fraction exhibited spasmogenicity upon spontaneous contractions, which was blocked in presence of verapamil, but remained unaffected by other tested antagonists. CONCLUSION: The Asphodelus tenuifolius crude extract possesses gut modulatory activity, which may normalize gut functions in diarrhea and constipation. The spasmolytic activity of the extract was found to be mediated through Ca+ 2 channel blocking action. The spasmogenic activity, found partitioned in aqueous fraction, possibly involves Ca+ 2 influx through voltage gated Ca+ 2 channels. The study supports ethnic uses of the plant in diarrhea and constipation.

Antidiarrheal activity of methanol extract of Sophora tonkinensis in mice and spasmolytic effect on smooth muscle contraction of isolated jejunum in rabbits.

Context: In China, the herb Sophora tonkinensis Gagnep. (Fabaceae, ST) (Committee of National Pharmacopeia. 2015) exhibits anti-inflammatory, antitumor, and antiviral effects. However, to date, there have been few studies on its gastrointestinal effect. Objective: The gastrointestinal effect of the methanol extract of ST rhizome (STR) was evaluated. Materials and methods: Study was conducted from February to December 2018. In vivo, antidiarrheal activity of STR (125, 250 and 500 mg/kg; orally) in castor oil-induced diarrheal mice was studied. In vitro, the effects of STR (0.01-10 mg/mL) on the isolated tissue preparations of rabbit jejunum were also investigated, the rabbit jejunum stripes were pre-contracted with Ach (10-5 M), K+ (60 mM) and tested in the presence of STR, the possible spasmolytic effect was analyzed in the pretreatment of the jejunum preparations with STR or verapamil in Ca2+-free high-K+ (60 mM) solution containing EDTA. Results: STR (125, 250 and 500 mg/kg) exhibited antidiarrheal activity. STR (0.01-10 mg/mL) completely relaxed spontaneously contracting, Ach (10-5 M) and high K+ (60 mM) induced contracted jejunum with an EC50 value of 0.66 (0.49-0.96), 0.39 (0.28-0.44) and 0.17 (0.10-0.21), similar to verapamil. Concentration-response curves of CaCl2 could be significantly moved to the right and down in the presence of STR (0.3, 1 mg/mL). Discussion and conclusions: Results suggest the presence of antidiarrheal activity and spasmolytic effects of STR, possibly mediated through Ca2+ channel blocking activity, providing the pharmacological basis for its traditional uses in gastrointestinal disorders.

Evaluation of the Antispasmodic and Antisecretory Activities of the 80% Methanol Extracts of Verbena officinalis L: Evidence From In Vivo Antidiarrheal Study.

Verbena officinalis L. has a folkloric repute for the management of digestive disorders, including diarrhea. However, the safety and efficacy of the plant material has not been scientifically validated yet. This study was, therefore, aimed to evaluate the overall antidiarrheal activity of the 80% methanol extracts of V officinalis in mice. The antidiarrheal activity of the 80% methanol extracts of the roots (R-80ME) and the leaves (L-80ME) of V officinalis was tested in castor oil-induced diarrhea in mice. R-80ME was further evaluated using charcoal meal and entero-pooling. In each test, group I and group II (controls) received 10 mL/kg distilled water and standard drug (5 mg/kg loperamide), respectively, whereas groups III, IV, and V (test groups) received 100, 200, and 400 mg/kg of the 80ME, respectively. The R-80ME at 200 mg/kg (P < .01) and 400 mg/kg (P < .001) significantly delayed the onset of diarrhea compared with negative control. Both R-80ME and L-80ME at 200 and 400 mg/kg significantly decreased the frequency of wet fecal outputs (P < .01). Generally, 70.24% inhibition of the number of wet fecal output was recorded at R-80ME 400 mg/kg. Results from the charcoal meal test revealed that the R-80ME at 200 (P < .01) and 400 mg/kg (P < .001) produced a significant antimotility effect. In entero-pooling test, the R-80ME, at 200 and 400 mg/kg doses (P < .01), showed a significant decline in both the volume and weight of intestinal contents. The maximum in vivo antidiarrheal index was determined to be 95.25 at dose of 400 mg/kg R-80ME. This study demonstrated that the 80ME, mainly the root extract, produced promising antidiarrheal activity and hence provides a scientific support for acclaimed traditional use of the plant material for treatment of diarrheal diseases.

Evaluation of In Vivo Antidiarrheal Activity of 80% Methanolic Leaf Extract of Osyris quadripartita Decne (Santalaceae) in Swiss Albino Mice.

The leaf of Osyris quadripartita is traditionally used for the management of diarrhea in different parts of Ethiopia. However, its use has not been scientifically validated for its efficacy. The aim of this study was to investigate antidiarrheal activity of hydroalcoholic leaf extract of O. quadripartita in mice models. Different doses of the methanolic leaf extract of O. quadripartita (100, 200, and 400 mg/kg) were tested for antidiarrheal activity using castor oil-induced diarrhea, enteropooling, and gastrointestinal motility models in Swiss Albino mice. The activities of the extract at different doses were compared with standard drugs and negative control groups of mice. The extract at all tested doses resulted in significant reduction ( P < .01) in number of wet feces, whereas significant reduction ( P < .01) in frequency of defecation in castor oil-induced diarrhea was seen at a dose of 400 mg/kg. It also showed a dose-dependent and significant reduction of volume of intestinal content in the enteropooling model at all tested doses and the observed results in 200 and 400 mg/kg were better than the standard drug, loperamide. However, significant antimotility effect was not observed at any of the tested doses. From these results we can conclude that methanolic leaf extract of O. quadripartita showed antidiarrheal activity.

Antidiarrhoeic effect and dereplication of the aqueous extract of Annona crassiflora (Annonaceae).

We investigated the antidiarrhoeic effect of the aqueous extract of Annona crassiflora leaves (AEAC). The AEAC decreased the diarrhoeic stools and enteropooling induced by castor oil, without altering total faecal output; moreover, the distance travelled by charcoal meal in the intestine was increased. Twenty-eight compounds were identified by LC-DAD-MS in the AEAC, including flavonoids, alkaloids and proanthocyanidins. In addition, two oligomeric series of condensed tannins of up to nine flavan-3-ol units were characterised by MALDI-MS. These data suggest that the antidiarrhoeic effect of the AEAC is related to its ability to inhibit intestinal secretion and/or to increase intestinal absorption. Moreover, the prokinetic effect of AEAC, together with its inhibitory effect on enteropooling induced by castor oil, explains why this extract decreased diarrhoeic faeces without altering the total faecal output. All these effects are in agreement with the pharmacological activity reported in the literature for many of the secondary metabolites identified.

Spasmolytic and antidiarrheal activities of Lippia thymoides (Verbenaceae) essential oil.

Lippia thymoides ('alecrim-do-mato' or 'alecrim-do-campo') is used in Brazilian folk medicine to treat various illnesses, including diarrhea. This work aimed to evaluate in vitro spasmolytic and in vivo antidiarrheal activities of the L. thymoides essential oil (OOS) and to correlate with the traditional use of this plant. In isolated guinea-pig ileum, OOS presented a concentration-dependent spasmolytic activity in preparations pre-contracted with KCl 40 mM [EC50 = 16.89 (11.56-24.66) µg/mL], and antagonized phasic contractions induced by 1 µM carbachol [IC50 = 42.71 (37.35-48.83) µg/mL] or histamine [IC50 = 32.38 (27.44-38.20) µg/mL]. In mice, OOS at 400 mg/kg reduced intestinal transit, at 200 and 400 mg/kg reduced total stool mass and at 400 mg/kg reduced intestinal fluid accumulation. It was shown that the antidiarrheal effect of OOS is related to the inhibition of smooth muscle contraction and may be due to the presence of major compound ß-caryophyllene in this essential oil.

Effects of Panax ginseng polysaccharides on the gut microbiota in mice with antibiotic-associated diarrhea.

Panax ginseng is a traditional medicinal plant used in most Asian countries to cure many diseases. The benefits of ginseng are due to its primary active component, polysaccharides. Gut microbiota dysbiosis is a worldwide problem associating with antibiotic use. The objective of this study was to investigate the effects of ginseng polysaccharides (WGP) on the diversity of the gut microbiota in mice with antibiotic-associated diarrhea. Compared to diarrhea mice, WGP significantly changed the composition and diversity of the gut microbiota. Specifically, WGP increased the relative abundance of the phylum Firmicutes and decreased the relative abundance of the phyla Bacteroidetes, Proteobacteria and Actinobacteria. At the genus level, WGP increased the relative abundance of Lactobacillus, Lactococcus, and Streptococcus, but decreased the relative abundance of Bacteroides. The key phylotype of beneficial bacteria in the gut microbiota that responded to WGP was Lactobacillus. In addition, WGP also reversed carbohydrate, amino acid and energy metabolism to normal levels, thereby promoting the recovery of the mucosal structure. Taken collectively, our results indicate that WGP altered the composition and diversity of the gut microbiota in mice with antibiotic-associated diarrhea, restored the gut microbiota, balanced metabolic processes, and promoted the recovery of the mucosa.

Antidiarrhoeal properties of Syzygium guineense leaf extract and identification of chemical constituents in its active column fractions.

Background Syzygium guineense (Myrtaceae) has been used in traditional medicine against various ailments, including diarrhoea. This study was conducted to scientifically evaluate the antidiarrheal effects of S. guineense extract and fractions. Methods An ethanol extract of S. guineense leaves was prepared and tested for its effect on small intestinal propulsion in mice and castor oil-induced fluid accumulation in rats. The extract was also evaluated for its effect on itopride-induced small intestine propulsion in mice. Column fractions were also investigated in rats and sub-fractions were tested for activity on spontaneous contractions of isolated rabbit jejunum. Results The results showed that the extract significantly (p<0.05) inhibited intrinsic small intestinal propulsion and itopride-induced propulsive activity, similar to atropine (0.3 mg/kg) although its inhibitory effect against castor oil-induced intestinal fluid accumulation and diarrhoea was statistically insignificant (p>0.05). Column separation yielded 14 fractions, with three fractions producing significant (p<0.001) inhibition of small intestinal propulsion. Sub-fractions 1, 7 and 16 obtained from an active column fraction also exhibited relaxant effects on isolated rabbit jejunum. Spectral analysis (proton, 13C NMR) of sub-fractions 7 and 16 revealed the presence of betulinic acid, ursolic acid, oleanolic acid in 7 and a mixture of luteolin and friedelane-type triterpenes in 16. Conclusions These findings provide scientific evidence that S. guineense leaf extract possess antidiarrhoeal activity and may be potentially beneficial in treatment diarrhoeal disease. The identified compounds may also be implicated in its antidiarrhoeal effects.