Medicinal grade opium tincture for severe diarrhea: effect revisited in observational study.

PURPOSE OF REVIEW: Chronic diarrhea is a common disorder that interferes with normal daily activities and results in poor quality of life. Fecal urgency and incontinence often necessitate clinical consultation, but the pathophysiological mechanisms are difficult to differentiate in a clinical setting. Therefore, drugs targeting the opioid receptors, such as diphenoxylate and loperamide, are typically used, as they reduce both gut motility and secretion. RECENT FINDINGS: For severe diarrhea, morphine-containing extemporaneous opium tincture drops have recently been reprofiled to a pharmaceutical. The drug is indicated for severe diarrhea in adults when other antidiarrheals do not give sufficient fecal emptying control. The pronounced effect is due to the liquid formulation with rapid onset as a drug dissolution step is avoided. A recent prospective, noninterventional study (CLARIFY) of patients treated with opioid drops demonstrates a rapid and sustained therapeutic effect. Tolerance does not develop for the antidiarrheal effect and no dependence was observed after discontinuation. SUMMARY: This mini-review discusses the use of opium derivates for treatment of diarrhea, with an emphasis on opium drops as a new medicinal grade opium for the use as additional treatment of severe diarrhea, emphasizing its mechanism of action and evaluation of the risk-benefit ratio in the clinical setting.

Diarrhoea of unknown cause: medical treatment in a stepwise mannerManagement of Idiopathic Diarrhoea Based on Experience of Step-Up Medical Treatment.

The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.

Chronic diarrhoea without an established cause is common.There are a small number of clinical trials, often with a limited number of patients or healthy volunteers.Treatment is often carried out on a trial-and-error basis, with considerable variation in the choice of treatment.There is a paucity of guidelines, and there is a gap in knowledge concerning treatment goals, such as the frequency, consistency and form of stool.The stepwise approach to the treatment of chronic idiopathic diarrhoea described in this article is based on clinical knowledge and experience.

Dietary rutin improves the antidiarrheal capacity of weaned piglets by improving intestinal barrier function, antioxidant capacity and cecal microbiota composition.

BACKGROUND: Early weaning is prone to damage intestinal barrier function, resulting in diarrhea, whereas rutin, as a natural flavonoid with multiple biological functions, shows potential in piglets. Therefore, the effects of dietary rutin on growth, antidiarrheal, barrier function, antioxidant status and cecal microbiota of weaned piglets were investigated with the control group (CON) (basal diet) and Rutin (basal diet+500 mg kg-1 rutin) groups fed for 14 days. RESULTS: The results showed that dietary 500 mg kg-1 rutin significantly decreased diarrhea index, serum diamine oxidase activity and total aerobic bacterial population in mesenteric lymph nodes, whereas it significantly increased the gain-to-feed ratio (G:F) and serum growth hormone content, jejunal villus height and villus height to crypt depth ratio, and also enhanced jejunal claudin-1 and zonula occludens-1 mRNA and protein expression. Meanwhile, dietary rutin significantly decreased inflammation-associated mRNA expression, malondialdehyde (MDA) content, swollen mitochondrial number and mitochondrial area in the jejunum, whereas it increased the total superoxide dismutase (T-SOD) and glutathione peroxidase activities and activated the Nrf2 signaling pathway. Moreover, dietary rutin significantly increased Firmicutes abundance and decreased Campylobacterota abundance, which were closely associated with the decreased diarrhea index and MDA content or increased Claudin-1 expression and T-SOD activity. CONCLUSION: Dietary 500 mg kg-1 rutin increased G:F by improving intestinal morphology, and alleviated diarrhea by enhancing intestinal barrier, which might be associated with the enhanced antioxidant capacity via activating the Nrf2/Keap1 signaling pathway and the improved cecal microbial composition in weaned piglets. © 2024 Society of Chemical Industry.

Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial.

BACKGROUND: The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but increased vomiting. METHODS: We randomly assigned 4500 children in India and Tanzania who were 6 to 59 months of age and had acute diarrhea to receive 5 mg, 10 mg, or 20 mg of zinc sulfate for 14 days. The three primary outcomes were a diarrhea duration of more than 5 days and the number of stools (assessed in a noninferiority analysis) and the occurrence of vomiting (assessed in a superiority analysis) within 30 minutes after zinc administration. RESULTS: The percentage of children with diarrhea for more than 5 days was 6.5% in the 20-mg group, 7.7% in the 10-mg group, and 7.2% in the 5-mg group. The difference between the 20-mg and 10-mg groups was 1.2 percentage points (upper boundary of the 98.75% confidence interval [CI], 3.3), and that between the 20-mg and 5-mg groups was 0.7 percentage points (upper boundary of the 98.75% CI, 2.8), both of which were below the noninferiority margin of 4 percentage points. The mean number of diarrheal stools was 10.7 in the 20-mg group, 10.9 in the 10-mg group, and 10.8 in 5-mg group. The difference between the 20-mg and 10-mg groups was 0.3 stools (upper boundary of the 98.75% CI, 1.0), and that between the 20-mg and 5-mg groups was 0.1 stools (upper boundary of the 98.75% CI, 0.8), both of which were below the noninferiority margin (2 stools). Vomiting within 30 minutes after administration occurred in 19.3%, 15.6%, and 13.7% of the patients in the 20-mg, 10-mg, and 5-mg groups, respectively; the risk was significantly lower in the 10-mg group than in the 20-mg group (relative risk, 0.81; 97.5% CI, 0.67 to 0.96) and in the 5-mg group than in the 20-mg group (relative risk, 0.71; 97.5% CI, 0.59 to 0.86). Lower doses were also associated with less vomiting beyond 30 minutes after administration. CONCLUSIONS: Lower doses of zinc had noninferior efficacy for the treatment of diarrhea in children and were associated with less vomiting than the standard 20-mg dose. (Funded by the Bill and Melinda Gates Foundation; ZTDT ClinicalTrials.gov number, NCT03078842.).

Antiperistaltic Transverse Coloplasty: A Salvage Procedure in Extensive Bowel and Colorectal Resections to Avoid Intestinal Failure.

INTRODUCTION: After extensive small and colon resections, quality of life can be affected. We propose the antiperistaltic transverse coloplasty as a solution that allows for preservation of the transverse colon after both right and left colectomies while achieving a tension-free colorectal anastomosis slowing the transit and increasing the absorption time, resulting in better stool consistency and quality of life compared with an ileorectal anastomosis. METHODS: This technique was performed in a 41-year-old woman with Goblet cell adenocarcinoma of the appendix with peritoneal metastasis. The transverse colon is rotated anticlockwise over the axis of the middle colic vessels toward the left parietocolic flank and relocated to the usual position of the descending colon. RESULTS: After 1 year of follow-up, the patient led a normal life without parenteral nutrition with five bowel movements per day and a weight gain of 15%. CONCLUSIONS: The use of an antiperistaltic transverse coloplasty may be worthwhile to perform in cases of extensive bowel resections during cytoreductive surgery leading to short-bowel syndrome to avoid a permanent stoma or intestinal failure and improve patient outcomes.

Rutin from Begonia roxburghii modulates iNOS and Sep A activity in treatment of Shigella flexneri induced diarrhoea in rats: An in vitro, in vivo and computational analysis.

In developing countries, diarrhoea is a major issue of concern, where consistent use of antibiotics has resulted in several side effects along with development of resistance among pathogens against these antibiotics. Since natural products are becoming the treatment of choice, therefore present investigation involves mechanistic evaluation of antidiarrhoeal potential of Begonia roxburghii and its marker rutin against Shigella flexneri (SF) induced diarrhoea in rats following in vitro, in vivo and in silico protocols. The roots of the plant are used as vegetable in the North East India and are also used traditionally in treating diarrhoea. Phytochemically standardized ethanolic extract of B. roxburghii (EBR) roots and its marker rutin were first subjected to in vitro antibacterial evaluation against SF. Diarrhoea was induced in rats using suspension of SF and various diarrhoeagenic parameters were examined after first, third and fifth day of treatment at 100, 200 and 300 mg/kg, p.o. with EBR and 50 mg/kg, p.o. with rutin respectively. Additionally, density of SF in stools, stool water content, haematological and biochemical parameters, cytokine profiling, ion concentration, histopathology and Na+/K+-ATPase activity were also performed. Molecular docking and dynamics simulation studies of ligand rutin was studied against secreted extracellular protein A (Sep A, PDB: 5J44) from SF and Inducible nitric oxide synthase (iNOS, PDB: 1DD7) followed by network pharmacology. EBR and rutin demonstrated a potent antibacterial activity against SF and also showed significant recovery from diarrhoea (EBR: 81.29 ± 0.91% and rutin: 75.27 ± 0.89%) in rats after five days of treatment. EBR and rutin also showed significant decline in SF density in stools, decreased cytokine expression, potential antioxidant activity, cellular proliferative nature and recovered ion loss due to enhanced Na+/K+-ATPase activity, which was also supported by histopathology. Rutin showed a very high docking score of -11.61 and -9.98 kcal/mol against iNOS and Sep A respectively and their stable complex was also confirmed through dynamics, while network pharmacology suggested that, rutin is quite capable of modulating the pathways of iNOS and Sep A. Thus, we may presume that rutin played a key role in the observed antidiarrhoeal activity of B. roxburghii against SF induced diarrhoea.

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.

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.

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.

The Cannabinoid Receptor Type 1 Positive Allosteric Modulator ZCZ011 Attenuates Naloxone-Precipitated Diarrhea and Weight Loss in Oxycodone-Dependent Mice.

Opioid use disorder reflects a major public health crisis of morbidity and mortality in which opioid withdrawal often contributes to continued use. However, current medications that treat opioid withdrawal symptoms are limited by their abuse liability or lack of efficacy. Although cannabinoid 1 (CB1) receptor agonists, including Δ9-tetrahydrocannabinol, ameliorate opioid withdrawal in both clinical and preclinical studies of opioid dependence, this strategy elicits cannabimimetic side effects as well as tolerance and dependence after repeated administration. Alternatively, CB1 receptor positive allosteric modulators (PAMs) enhance CB1 receptor signaling and show efficacy in rodent models of pain and cannabinoid dependence but lack cannabimimetic side effects. We hypothesize that the CB1 receptor PAM ZCZ011 attenuates naloxone-precipitated withdrawal signs in opioid-dependent mice. Accordingly, male and female mice given an escalating dosing regimen of oxycodone, a widely prescribed opioid, and challenged with naloxone displayed withdrawal signs that included diarrhea, weight loss, jumping, paw flutters, and head shakes. ZCZ011 fully attenuated naloxone-precipitated withdrawal-induced diarrhea and weight loss and reduced paw flutters by approximately half, but its effects on head shakes were unreliable, and it did not affect jumping behavior. The antidiarrheal and anti-weight loss effects of ZCZ0111 were reversed by a CB1 not a cannabinoid receptor type 2 receptor antagonist and were absent in CB1 (-/-) mice, suggesting a necessary role of CB1 receptors. Collectively, these results indicate that ZCZ011 completely blocked naloxone-precipitated diarrhea and weight loss in oxycodone-dependent mice and suggest that CB1 receptor PAMs may offer a novel strategy to treat opioid dependence. SIGNIFICANCE STATEMENT: Opioid use disorder represents a serious public health crisis in which current medications used to treat withdrawal symptoms are limited by abuse liability and side effects. The CB1 receptor positive allosteric modulator (PAM) ZCZ011, which lacks overt cannabimimetic behavioral effects, ameliorated naloxone-precipitated withdrawal signs through a CB1 receptor mechanism of action in a mouse model of oxycodone dependence. These results suggest that CB1 receptor PAMs may represent a viable strategy to treat opioid withdrawal.

Evaluation of a bivalent recombinant vaccine candidate targeting norovirus and rotavirus: Antibodies to rotavirus NSP4 exert antidiarrheal effects without virus neutralization.

We previously found that when tandemly expressed with SR69A -VP8*, nonstructural protein 4 (NSP4) of the rotavirus Wa strain exerts a minor effect on elevating the antibody responses targeting the rotavirus antigen VP8* of the 60-valent nanoparticle SR69A -VP8* but could fully protect mice from diarrhea induced by the rotavirus strain Wa. In this study, we chose comparably less immunogenic norovirus 24-valent P particles with homogenous (i.e., VP8* from rotavirus) and heterogeneous (i.e., protruding domain of norovirus) antigens and in more challenging rotavirus SA11 strain-induced diarrhea mouse models to evaluate its main role in recombinant gastroenteritis virus-specific vaccines. The results showed that although as an adjuvant NSP4 exerted limited effects on the elevation of norovirus-specific or VP8*-specific neutralizing antibody production, as an antigen it could confer potent protection, particularly when synergized with VP8*, in rotavirus SA11 strain-induced diarrhea mouse models, possibly blocking the invasion of the intestinal wall by enterotoxin. NSP4 may be unnecessary for other recombinant vaccines as adjuvants, and its display mode should be evaluated specifically to avoid blocking coexpressed antigens in the norovirus P particles.

Cardiac Electropharmacological Effects of Antidiarrheal Drug Loperamide and Its Antidote Naloxone in Anesthetized Guinea Pigs.

Cardiac electropharmacological effects of an antidiarrheal drug loperamide and its antidote naloxone were assessed in isoflurane-anesthetized guinea pigs. Intravenous administration of loperamide at 0.01-0.1 mg/kg did not affect parameters of electrocardiogram (ECG) or monophasic action potential (MAP) of the right ventricle. Additional administration of loperamide at 1 mg/kg prolonged the QT interval and MAP duration of the ventricle accompanied with increments of the PQ interval and QRS width. The potency of loperamide for QT-interval prolongation was about 100-times lower than that of dofetilide, in spite that similar inhibitory effects on the human Ether-a-go-go Related Gene (hERG) K+ channels have been reported between loperamide and dofetilide, implying lower accessibility of loperamide to the K+ channels. Intravenous administration of naloxone at 0.003-0.3 mg/kg, which effectively inhibits µ-opioid receptors, did not affect ECG parameters including QT interval or MAP duration. Furthermore, the loperamide-induced cardiac electrophysiological changes were not modified in the presence of naloxone at 0.3 mg/kg. These results suggest that loperamide has a potential to delay cardiac conduction and repolarization in the in vivo condition. Since naloxone did not modify ECG parameters and loperamide-induced ECG changes, naloxone is confirmed to possess acceptable cardiac safety when used as an antidote.

Acute Diarrhea in Adults.

Acute diarrheal disease accounts for 179 million outpatient visits annually in the United States. Diarrhea can be categorized as inflammatory or noninflammatory, and both types have infectious and noninfectious causes. Infectious noninflammatory diarrhea is often viral in etiology and is the most common presentation; however, bacterial causes are also common and may be related to travel or foodborne illness. History for patients with acute diarrhea should include onset and frequency of symptoms, stool character, a focused review of systems including fever and other symptoms, and evaluation of exposures and risk factors. The physical examination should include evaluation for signs of dehydration, sepsis, or potential surgical processes. Most episodes of acute diarrhea in countries with adequate food and water sanitation are uncomplicated and self-limited, requiring only an initial evaluation and supportive treatment. Additional diagnostic evaluation and management may be warranted when diarrhea is bloody or mucoid or when risk factors are present, including immunocompromise or recent hospitalization. Unless an outbreak is suspected, molecular studies are preferred over traditional stool cultures. In all cases, management begins with replacing water, electrolytes, and nutrients. Oral rehydration is preferred; however, signs of severe dehydration or sepsis warrant intravenous rehydration. Antidiarrheal agents can be symptomatic therapy for acute watery diarrhea and can help decrease inappropriate antibiotic use. Empiric antibiotics are rarely warranted, except in sepsis and some cases of travelers' or inflammatory diarrhea. Targeted antibiotic therapy may be appropriate following microbiologic stool assessment. Hand hygiene, personal protective equipment, and food and water safety measures are integral to preventing infectious diarrheal illnesses.

Can diarrhea affect the pharmacokinetics of racecadotril in neonatal calves?

This study was aimed to determine the pharmacokinetics of antisecretory-acting racecadotril, used in the treatment of diarrhea in humans and dogs, following oral administration in both neonatal calves with healthy and neonatal calves with infectious diarrhea. The study was carried out on a total of 24 Holstein calves (2-20 days), of which 6 were healthy and 18 were infectious diarrhea. Calves with infectious diarrhea were divided into 3 groups according to the infectious agent (Escherichia coli, Cryptosporidium parvum, and rotavirus/coronavirus). Racecadotril was administered orally at 2.5 mg/kg dose to calves. The plasma concentrations of racecadotril and its main active metabolite (thiorphan) were determined using HPLC-UV. The pharmacokinetic parameters were analyzed using the non-compartmental method. In healthy calves, the t1/2ʎz , Cmax , Tmax, and AUC0-12 of racecadotril were determined 4.70 h, 377 ng/ml, 0.75 h, and 1674 h × ng/ml, respectively. In the plasma of calves with infectious diarrhea, racecadotril and thiorphan were only detected at the sampling time from 0.25 to 1.5 h. As in calves with infectious diarrhea, thiorphan in plasma was only detected in healthy calves from 0.25 to 1.5 h. Racecadotril showed a large distribution volume, rapid elimination, and low metabolism to thiorphan in healthy calves.

Aegle marmelos (L.) Correa: An Underutilized Fruit with High Nutraceutical Values: A Review.

Aegle marmelos (L.) Correa (Bael) fruit, a member of the Rutaceae family, is a major cultivated fruit plant in tropical and subtropical regions in countries of southeast Asia. Bael fruit has been a major topic for studies in recent years mainly due to its high nutritional (carbohydrates, proteins, minerals, and vitamins) value and presence of various phytochemicals, which attributed to its high medicinal value. These phytochemicals include various compounds, e.g., alkaloids, flavonoids, and phenolic acids (protocatechuic acid, gallic, and ellagic acid). The fruit extract of bael has been also an important study area for its pharmacological activities, including antidiarrheal, antioxidant, antidiabetic, hepatoprotective, radioprotective, anticancer, antiulcer properties. The current review mainly highlighted the nutritional and pharmacological activities of bael fruit. The nutritional profile and phytochemical profile were discussed in the review, along with their concentration in the fruit. Moreover, the experiments carried out in vivo and in vitro of bael fruit extracts with respect to their pharmacological activities were also discussed in the article. The recent literature based on nutritional and pharmacological values of bael fruit showed its high potential as a food and pharmaceutical product. Despite having high nutritional and pharmacological value, research related to molecular mechanisms of bael fruit is still limited, and clinical trials are needed to ensure its safety as a product in the food and pharma industries.

GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica.

This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. The phytochemicals were detected using gas chromatography−mass spectrometry (GC−MS) while the in vivo antidiarrheal test was done using Swiss albino mice. To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. GC−MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. The highest antidiarrheal effect was observed with loperamide (p < 0.01), used as a control drug. In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders.

A Literature Review of Artocarpus lacucha Focusing on the Phytochemical Constituents and Pharmacological Properties of the Plant.

Studies have shown that approximately two-thirds of the plant species in the world have some medicinal value. Artocarpus lakoocha is a synonym for Artocarpus lacucha and is a plant that can be found in Indonesia. This medicinal plant has been used to treat many diseases. (1) Objective: This article discusses the scientific investigations carried out on A. lacucha, namely the plant's chemical content, pharmacological activity, and active compounds. (2) Methods: The design of this study was based on an article that was a review of previous research. A search for relevant publications over the past ten years (2012-2022) using data from Pubmed, Proquest, Ebsco, ScienceDirect, and Google Scholar resulted in the discovery of 369 articles. (3) Results: Fifty relevant articles investigate A. lacucha's substances and their applications in the health field. The presence of secondary metabolites and bioactive compounds has been reported, which is evidence that A. lacucha possesses antidiarrheal, immunostimulant, anticholesterol, and hepatoprotective agents. (4) Conclusions: Mobe (A. lacucha) is a plant native to North Sumatra, Indonesia. This plant is efficacious as an antioxidant, antibacterial, antidiarrheal, anti-inflammatory, analgesic, antinociceptive, schistosomicidal, hepatoprotective, neuroprotective, cytotoxic, antiglycation, and anticholesterol, and can also be used for anti-aging and wound healing. In addition to its various benefits, it turns out that this plant also has many active compounds that are useful to the health sector, especially the pharmaceutical field.

The Detailed Pharmacodynamics of the Gut Relaxant Effect and GC-MS Analysis of the Grewia tenax Fruit Extract: In Vivo and Ex Vivo Approach.

The study was performed to assess and rationalize the traditional utilization of the fruit part of Grewia tenax (G. tenax). The phytoconstituents present in the methanolic extract were analyzed using Gas-Chromatography-Mass Spectroscopy (GC-MS), while the anti-diarrheal activity was investigated in the Swiss albino mice against castor oil-provoked diarrhea in vivo. The antispasmodic effect and the possible pharmacodynamics of the observed antispasmodic effect were determined in an isolated rat ileum using the organ bath setup as an ex vivo model. GC-MS findings indicate that G. tenax is rich in alcohol (6,6-dideutero-nonen-1-ol-3) as the main constituent (20.98%), while 3-Deoxy-d-mannoic lactone (15.36%) was detected as the second major constituents whereas methyl furfural, pyranone, carboxylic acid, vitamin E, fatty acid ester, hydrocarbon, steroids, sesquiterpenes, phytosterols, and ketones were verified as added constituents in the methanolic extract. In mice, the orally administered G. tenax inhibited the diarrheal episodes significantly (p < 0.05) at 200 mg/kg (40% protection), and this protection was escalated to 80% with the next higher dose of 400 mg/kg. Loperamide (10 mg/kg), a positive control drug, imparted 100% protection, whereas no protection was shown by saline. In isolated rat ileum, G. tenax completely inhibited the carbamylcholine (CCh; 1 µM) and KCl (high K+; 80 mM)-evoked spasms in a concentrations-mediated manner (0.03 to 3 mg/mL) by expressing equal potencies (p > 0.05) against both types of evoked spasms, similar to papaverine, having dual inhibitory actions at phosphodiesterase enzyme (PDE) and Ca2+ channels (CCB). Similar to papaverine, the inhibitory effect of G. tenax on PDE was further confirmed indirectly when G. tenax (0.1 and 0.3 mg/mL) preincubated ileal tissues shifted the isoprenaline-relaxation curve towards the left. Whereas, pre-incubating the tissue with 0.3 and 1 mg/mL of G. tenax established the CCB-like effect by non-specific inhibition of CaCl2−mediated concentration-response curves towards the right with suppression of the maximum peaks, similar to verapamil, a standard CCB. Thus, the present investigation revealed the phytochemical constituents and explored the detailed pharmacodynamic basis for the curative use of G. tenax in diarrhea and hyperactive gut motility disorders.

Chemical and Pharmacological Profiling of Wrightia coccinea (Roxb. Ex Hornem.) Sims Focusing Antioxidant, Cytotoxic, Antidiarrheal, Hypoglycemic, and Analgesic Properties.

The aim of the study was to conduct phytochemical and pharmacological investigations of Wrightia coccinea (Roxb. ex Hornem.) Sims via several in vitro, in vivo, and in silico models. A total of four compounds were identified and isolated from the methanol extract of the bark and the methanol extract of the seed pulp of W. coccinea through successive chromatographic techniques and were characterized as 3ß-acetyloxy-olean-12-en-28-ol (1), wrightiadione (2), 22ß-hydroxylupeol (3), and ß-sitosterol (4) by spectroscopic analysis. The aqueous fraction of the bark and chloroform fraction of the fruits provided the most potent antioxidant capacity (IC50 = 7.22 and 4.5 µg/mL, respectively) in DPPH free radical scavenging assay compared with the standard ascorbic acid (IC50 = 17.45 µg/mL). The methanol bark extract and the methanol fruit coat extract exerted anti-diarrheal activity by inhibiting 74.55 ± 0.67% and 77.78 ± 1.5% (mean ± SEM) of the diarrheal episode in mice, respectively, after four hours of loading the samples. In the hypoglycemic test, the methanol bark extract and the methanol fruit coat extract (400 mg/kg) produced a significant (p < 0.05) reduction in the blood glucose level in mice. Both doses of the plant extracts (200 mg/kg and 400 mg/kg) used in the study induced a significant (p < 0.05) increase in pain reaction time. The in vitro and in vivo findings were supported by the computational studies. The isolated compounds exhibited higher binding affinity compared with the standard drugs towards the active binding sites of glutathione reductase, epidermal growth factor receptor (EGFR), kappa opioid receptor, glucose transporter 3 (GLUT 3), Mu opioid receptor, and cyclooxygenase 2 (COX-2) proteins due to their potent antioxidant, cytotoxic, anti-diarrheal, hypoglycemic, and central and peripheral analgesic properties, respectively. The current findings concluded that W. coccinea might be a potential natural source for managing oxidative stress, diarrhea, hyperglycemia, and pain. Further studies are warranted for extensively phytochemical screening and establishing exact mechanisms of action.

Antidiarrheal and Antibacterial Activities of Monterey Cypress Phytochemicals: In Vivo and In Vitro Approach.

Monterey cypress (Cupressus macrocarpa) is a decorative plant; however, it possesses various pharmacological activities. Therefore, we explored the phytochemical profile of C. macrocarpa root methanol extract (CRME) for the first time. Moreover, we investigated its antidiarrheal (in vivo), antibacterial, and antibiofilm (in vitro) activities against Salmonella enterica clinical isolates. The LC-ESI-MS/MS analysis of CRME detected the presence of 39 compounds, besides isolation of 2,3,2″,3″-tetrahydro-4'-O-methyl amentoflavone, amentoflavone, and dihydrokaempferol-3-O-α-l-rhamnoside for the first time. Dihydrokaempferol-3-O-α-l-rhamnoside presented the highest antimicrobial activity and the range of values of MICs against S. enterica isolates was from 64 to 256 µg/mL. The antidiarrheal activity of CRME was investigated by induction of diarrhea using castor oil, and exhibited a significant reduction in diarrhea and defecation frequency at all doses, enteropooling (at 400 mg/kg), and gastrointestinal motility (at 200, 400 mg/kg) in mice. The antidiarrheal index of CRME increased in a dose-dependent manner. The effect of CRME on various membrane characters of S. enterica was studied after typing the isolates by ERIC-PCR. Its impact on efflux and its antibiofilm activity were inspected. The biofilm morphology was observed using light and scanning electron microscopes. The effect on efflux activity and biofilm formation was further elucidated using qRT-PCR. A significant increase in inner and outer membrane permeability and a significant decrease in integrity and depolarization (using flow cytometry) were detected with variable percentages. Furthermore, a significant reduction in efflux and biofilm formation was observed. Therefore, CRME could be a promising source for treatment of gastrointestinal tract diseases.