Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study.

Well-characterized and standardized extracts of a Mexican genotype of Ganoderma lucidum (Gl), a medicinal mushroom, cultivated on oak sawdust (Gl-1) or oak sawdust plus acetylsalicylic acid (Gl-2, ASA), have been shown to exert antioxidant, hypocholesterolemic, anti-inflammatory, prebiotic, and anticancer properties. However, toxicity analyses still need to be carried out. Different doses of these Gl-1 or Gl-2 extracts were administered to Wistar rats for 14 days in a repeated dose oral toxicity study. We assessed the external clinical signs, biochemical parameters, liver and kidney tissues, injury and inflammation biomarkers, gene expression, inflammatory responses, proinflammatory mediators, and gut microbiota. Gl extracts had no significant adverse, toxic or harmful effects on male and female rats compared to the control groups. No injury or dysfunction were recorded in the kidney or liver, as there were no significant abnormal variations in organ weight, tissue histopathology, serum biochemical parameters (C-reactive protein, creatinine, urea, glucose, ALT and AST transaminases, TC, LDL-c, TG, HDL-c), urinary parameters (creatinine, urea nitrogen, albumin, the albumin-to-creatinine ratio, glucose), injury and inflammatory biomarkers (KIM-1/TIM-1, TLR4, and NF-кB protein expression; IL-1ß, TNF-α and IL-6 gene expression), or the expression of genes linked to cholesterol metabolism (HMG-CoA, Srebp2, Ldlr). Gl-1 and Gl-2 extracts showed prebiotic effects on the gut microbiota of male and female Wistar rats. Bacterial diversity and relative bacterial abundance (BRA) increased, positively modulating the Firmicutes/Bacteroidetes ratio. The ASA (10 mM) added to the substrate used for mushroom cultivation changed properties and effects of the Gl-2 extract on Wistar rats. The no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg body weight/day of Gl-1 or Gl-2 extracts. Clinical trials are recommended for further exploring the potential therapeutic applications of studied extracts.

Role of baicalin as a potential therapeutic agent in hepatobiliary and gastrointestinal disorders: A review.

Baicalin is a natural bioactive compound derived from Scutellaria baicalensis, which is extensively used in traditional Chinese medicine. A literature survey demonstrated the broad spectrum of health benefits of baicalin such as antioxidant, anticancer, anti-inflammatory, antimicrobial, cardio-protective, hepatoprotective, renal protective, and neuroprotective properties. Baicalin is hydrolyzed to its metabolite baicalein by the action of gut microbiota, which is further reconverted to baicalin via phase 2 metabolism in the liver. Many studies have suggested that baicalin exhibits therapeutic potential against several types of hepatic disorders including hepatic fibrosis, xenobiotic-induced liver injury, fatty liver disease, viral hepatitis, cholestasis, ulcerative colitis, hepatocellular and colorectal cancer. During in vitro and in vivo examinations, it has been observed that baicalin showed a protective role against liver and gut-associated abnormalities by modifying several signaling pathways such as nuclear factor-kappa B, transforming growth factor beta 1/SMAD3, sirtuin 1, p38/mitogen-activated protein kinase/Janus kinase, and calcium/calmodulin-dependent protein kinase kinaseß/adenosine monophosphate-activated protein kinase/acetyl-coenzyme A carboxylase pathways. Furthermore, baicalin also regulates the expression of fibrotic genes such as smooth muscle actin, connective tissue growth factor, ß-catenin, and inflammatory cytokines such as interferon gamma, interleukin-6 (IL-6), tumor necrosis factor-alpha, and IL-1ß, and attenuates the production of apoptotic proteins such as caspase-3, caspase-9 and B-cell lymphoma 2. However, due to its low solubility and poor bioavailability, widespread therapeutic applications of baicalin still remain a challenge. This review summarized the hepatic and gastrointestinal protective attributes of baicalin with an emphasis on the molecular mechanisms that regulate the interaction of baicalin with the gut microbiota.

Meta-inhibition of ocular and gastrointestinal dysfunctions by phenolic-rich fraction of Croton zambsicus leaves in a rat model exposed to chronic mixed metals.

PURPOSE: This study was aimed at investigating the protective effect of antioxidant-rich fraction of Croton zambsicus (C-ZAMB) leaves on ocular-gastrointestinal dysfunction in rats exposed to environmental mixed-metal (EOMABRSL). MATERIALS AND METHODS: The rats were divided into five (n = 10) groups. Group I designates the control which received 0.5 mL of distilled water. Group II and III received 0.5 mL of EOMABRSL for 98 days (non-withdrawal) and 70 days (withdrawal for 28 days), respectively. Group IV received 0.5 mL EOMABRSL for 70 days and 400 mg/kg C-ZAMB fraction for 28 days. Group V received 400 mg/kg C-ZAMB only for 28 days via oral route. RESULTS: Exposure of the animals to EOMARBSL for 98 days and 70 days significantly up-regulated the activities of ocular-gastrointestinal aldolase-reductase, α-amylase, α-glucosidase and eco-51-nucleotidase with corresponding depletion of lactate dehydrogenase activity. Furthermore, exposure to EOMABRSL significantly altered the antioxidant proteins with up-production of MDA content. Apparently, management with 400 mg/kg C-ZAMB fraction significantly inhibited the key markers linked with ocular-gastrointestinal disorders. CONCLUSION: Hence, this study underscores the biochemical mechanisms for managing ocular-gastrointestinal lesions by 400 mg/kg C-ZAMB fraction on exposure to mixture of environmental metals.

Vitamin D Signaling in Gastro-Rheumatology: From Immuno-Modulation to Potential Clinical Applications.

In the last decades, the comprehension of the pathophysiology of bone metabolism and its interconnections with multiple homeostatic processes has been consistently expanded. The branch of osteoimmunology specifically investigating the link between bone and immune system has been developed. Among molecular mediators potentially relevant in this field, vitamin D has been recently pointed out, and abnormalities of the vitamin D axis have been described in both in vitro and in vivo models of inflammatory bowel diseases (IBD) and arthritis. Furthermore, vitamin D deficiency has been reported in patients affected by IBD and chronic inflammatory arthritis, thus suggesting the intriguing possibility of impacting the disease activity by the administration vitamin D supplements. In the present review, the complex interwoven link between vitamin D signaling, gut barrier integrity, microbiota composition, and the immune system was examined. Potential clinical application exploiting vitamin D pathway in the context of IBD and arthritis is presented and critically discussed. A more detailed comprehension of the vitamin D effects and interactions at molecular level would allow one to achieve a novel therapeutic approach in gastro-rheumatologic inflammatory diseases through the design of specific trials and the optimization of treatment protocols.

Maternal vitamin A deficiency impairs cholinergic and nitrergic neurons, leading to gastrointestinal dysfunction in rat offspring via RARß.

AIMS: Many gastrointestinal (GI) disorders are developmental in origin and are caused by abnormal enteric nervous system (ENS) formation. Maternal vitamin A deficiency (VAD) during pregnancy affects multiple central nervous system developmental processes during embryogenesis and fetal life. Here, we evaluated whether maternal diet-induced VAD during pregnancy alone can cause changes in the ENS that lead to GI dysfunction in rat offspring. MAIN METHODS: Rats were selected to construct animal models of normal VA, VA deficiency and VA supplementation. The fecal water content, total gastrointestinal transmission time and colonic motility were measured to evaluate gastrointestinal function of eight-week-old offspring rats. The expression levels of RARß, SOX10, cholinergic (ChAT) and nitrergic (nNOS) enteric neurons in colon tissues were detected through western blot and immunofluorescence. Primary enteric neurospheres were treated with retinoic acid (RA), infection with Ad-RARß and siRARß adenovirus, respectively. KEY FINDINGS: Our data revealed marked reductions in the mean densities of cholinergic and nitrergic enteric neurons in the colon and GI dysfunction evidenced by mild intestinal flatulence, increased fecal water content, prolonged total GI transit time and reduced colon motility in adult offspring of the VAD group. Interestingly, maternal VA supplementation (VAS) during pregnancy rescued these changes. In addition, in vitro experiments demonstrated that exposure to appropriate doses of RA promoted enteric neurosphere differentiation into cholinergic and nitrergic neurons, possibly by upregulating RARß expression, leading to enhanced SOX10 expression. SIGNIFICANCE: Maternal VAD during pregnancy is an environmental risk factor for GI dysfunction in rat offspring.

SIRT1 inhibitors mitigate radiation-induced GI syndrome by enhancing intestinal-stem-cell survival.

High-dose radiation exposure induces gastrointestinal (GI) stem cell death, resulting in denudation of the intestinal mucosa and lethality from GI syndrome, for which there is currently no effective therapy. Studying an intestinal organoid-based functional model, we found that Sirtuin1(SIRT1) inhibition through genetic knockout or pharmacologic inhibition significantly improved mouse and human intestinal organoid survival after irradiation. Remarkably, mice administered with two doseages of SIRT1 inhibitors at 24 and 96 h after lethal irradiation promoted Lgr5+ intestinal stem cell and crypt recovery, with improved mouse survival (88.89% of mice in the treated group vs. 0% of mice in the control group). Moreover, our data revealed that SIRT1 inhibition increased p53 acetylation, resulting in the stabilization of p53 and likely contributing to the survival of intestinal epithelial cells post-radiation. These results demonstrate that SIRT1 inhibitors are effective clinical countermeasures to mitigate GI toxicity from potentially lethal radiation exposure.

Potential preventive and therapeutic effect of Chinese herb rhubarb (da huang) for intensive care unit/pediatric intensive care unit gastrointestinal failure patients: A protocol for systematic review.

INTRODUCTION: The Chinese herb da huang (DH) (Rhubarb) is commonly used for GIF intensive care unit (ICU)/pediatric intensive care unit (PICU) gastrointestinal failure (GIF) patients in China. However, the potential preventive and therapeutic effect of DH in these patients has not yet been studied systematically. OBJECTIVES: The aim of this study was to evaluate the preventive and therapeutic effects of DH in treating ICU/PICU GIF patients with the most recent evidence. METHODS: We systematically searched 7 databases from inception to March 30, 2018. RevMan 5.3 software was used to perform a meta-analysis. GRADE methodology was applied to evaluate the quality of evidence for each outcome. The review protocol was registered on PROSPERO (CRD42018092710) in advance. RESULTS: Seven studies comprising 788 pediatric or adult participants were included in this analysis. Three indicators, including GIF occurrence rates (gastrointestinal mucosal hemorrhage, enteroplegia), multiple organ dysfunction syndrome (MODS)-related items (occurrence rates of MODS, mortality rates of MODS) and duration in the ICU was analyzed. The GIF occurrence rate meta-analysis result was (RR 0.47, CI 95% 0.37-0.60; P = .95); MODS related items indicator result was (RR 0.44, CI 95% 0.33-0.59; P = .41); ICU duration ICU result was (RR -2.87, CI 95% -3.53--2.21; P = .40). The safety of Chinese herb DH (Rhubarb) remains unclear. CONCLUSION: Current evidence suggests that the Chinese herb rhubarb (DH) powder combined with Western medicine was inferior to Western medicine alone in terms of preventive and therapeutic effects in ICU/PICU patients in terms of decreasing GIF occurrence rates (gastrointestinal mucosal hemorrhage and enteroplegia), occurrence rates of MODS, mortality from MODS, and shortened duration time in the ICU/PICU. However, larger sample sizes and rigorously-designed studies are necessary to conclusively determine the association between DH powder and outcomes in ICU/PICU GIF patients.

Lower gastrointestinal symptoms and symptoms-based triaging systems are poor predictors of clinical significant disease on colonoscopy.

Introduction: Lower gastrointestinal symptoms (LGS) are a common cause of referral to the gastroenterology service. International guidelines are available to prioritise referrals. Some studies have reported that symptoms alone are a poor marker of clinically significant disease (CSD) but symptoms remain the main way to prioritise referrals in routine clinical practice. Aims/background: To correlate LGS with colonoscopy findings in an unselected patient cohort and to investigate whether using National Institute for Health and Care Excellence (NICE) guidelines improve risk stratification. Method: Colonoscopy data over a 2-year period were obtained from our endoscopy database. Only patients with assessment of symptoms as their primary indication for colonoscopy were included. Patient records were retrospectively reviewed. Exclusion criteria: known inflammatory bowel disease (IBD), familial cancer syndromes, polyp and colorectal cancer (CRC) surveillance, and prior colonoscopy within 5 years. Demographics, symptoms and colonoscopy findings were recorded and analysed. Results: 1116 cases were reviewed; 493 (44%) males, age 54.3 years (16-91). CSD occurred in only 162 (14.5%); CRC 19 (1.7%), high-risk adenoma 40 (3.6%), inflammation 97 (8.7%) (IBD 65 (5.8%), microscopic colitis 9 (0.8%) and indeterminate-inflammation 23 (2%)), angiodysplasia 6 (0.5%). Diarrhoea gave the highest diagnostic yield for CSD of 5.3% (OR 3.15, 95% CI 2.2 to 4.7, p<0.001), followed by PR bleeding, 2.9% (OR 1.9, 95% CI 1.24 to 2.9, p=0.003). Weight loss gave the lowest diagnostic yield of 0.4%; (OR 0.79, 95% CI 0.28 to 2.24, p=0.65). 592 (53%) and 517 (46%) fitted the NICE guidelines for CRC and IBD, respectively. Using NICE positivity improved detection but overall yield remained low 3% vs 0.4% (OR 7.71, 95% CI 1.77 to 33.56, p=0.0064) for CRC, and 9% vs 2.8% (OR 3.5, 95% CI 1.99 to 6.17, p<0.0001) for IBD. Conclusions: The overall prevalence of CSD in our unselected symptomatic patients is low (14.5%). A holistic approach including combining symptoms and demographics with novel tools including stool biomarkers and minimally invasive colonoscopy alternatives should be applied to avoid unnecessary colonoscopy.

Herbal formula improves upper and lower gastrointestinal symptoms and gut health in Australian adults with digestive disorders.

Gastrointestinal (GI) problems affect half of Western populations. Symptoms can vary from frequent reflux to irritable bowel syndrome. The Nutrition Care (NC) Gut Relief Formula contains a combination of herbs and nutrients including curcumin, Aloe vera, slippery elm, guar gum, pectin, peppermint oil, and glutamine shown to benefit the GI system. The 16-week pre-post study tested the hypothesis that the NC Gut Relief Formula would be tolerable and effective in improving GI symptoms and gut health in adults with digestive disorders. A total of 43 participants completed the study. After a control phase, participants took 5 g/d and then 10 g/d of the formula for 4 weeks. GI symptoms and GI health were assessed by a series of validated questionnaires, for example, Leeds Dyspepsia Questionnaire, Bristol Stool Chart, Birmingham IBS Symptom Questionnaire, and by intestinal permeability and gut microbiota profile. The NC Gut Relief Formula significantly improved the frequency and severity of upper and lower GI symptoms by 60%-80%, including indigestion, heartburn, nausea, constipation or diarrhea, abdominal pain, and troublesome flatulence, and significantly improved physical functioning, energy levels, mood, and sleep by 60%-80%. All participants with normal stool, 90% with hard stool, and 66% with soft stool recovered from intestinal permeability, evident by normal lactulose to mannitol ratios. The NC Gut Relief Formula generally improved microbial profile, with a marked increase in Lactobacillus, Clostridium, and Faecalibacterium prausnitzii. Almost half of the participants with upper GI symptoms taking proton pump inhibitors for heartburn no longer required proton pump inhibitors at the end of the study. A third of participants were able to reintroduce food triggers, such as fermentable oligosaccharides, disaccharides, monosaccharides, and polyols garlic, onion, and beans, or reflux-causing acidic/spicy foods, for example, citrus, tomato, and caffeine, in their diet after 3 months without symptom aggravation. The NC Gut Relief Formula significantly improved GI symptoms and associated quality of life over 3 months while reducing intestinal permeability, improving the microbial profile, reducing the need for reflux medication, and enabling the consumption of previous food triggers.

Comorbidity and polypharmacy in patients with breast cancer.

BACKGROUND: Cancer sufferers are aged ≥ 65 years, but research has focused infrequently on elderly patients with the majority of cancer. We aimed not only to determine the frequency of comorbidity and polypharmacy, but also to present the discrepiancies in elderly versus non-elderly patients with breast cancer. METHODS: A total of 352 female patients aged over 18 years, 252 non-elderly and 100 elderly, followed-up in the oncology department of a tertiary hospital between January 2016 and September 2019 were retrospectively screened. Demographic data, comorbidity and medications of the patients were recorded hospital data processing system. Polypharmacy was defined as the use of ≥ 5 different medications. RESULTS: The most common four chronic diseases in both non-elderly and elderly groups were muscle-joint-bone disease, gastrointestinal diseases, diabetes mellitus and hypertension. The most common four prescribed drugs were NSAID, adjuvant endocrine therapy, PPI, and vitamin D or/and calcium in non-elderly group while those were ACEI-ARB, PPI, NSAID, and diuretics in elderly one. The frequency of polypharmacy was 50% (n = 126) in the non-elderly patients and 74% (n = 74) in the elderly ones. These were considered statistically significant (p < 0.001). The mean number of prescription medication categories reported was 5.02 (SD = 2.90; range 0-14) in non-elderly group whereas those was 6.83 (SD = 3.18; range 0-15) in elderly one (p < 0.001). The mean of ages were 47.9 years (without polypharmacy) and 51.3 years (with polypharmacy) in non-elderly patients while those are, respectively, 70.9 years and 74.7 years in elderly ones. These were considered statistically significant (respectively; p = 0.006, p = 0.009). CONCLUSIONS: We first gained to raise awareness in the literature of comorbidity and polypharmacy in patients with breast cancer and to compare between the elderly and non-elderly participants. For the effectiveness of cancer treatment, importance in geriatric population, attention to drug-drug interaction, such studies should be considered during clinical practice.

Ultrasonic extraction, structural characterization, and bioactivities of nonstarch polysaccharides from red yeast rice.

Red yeast rice (RYRP) has been utilized for coloring food, brewing wine, and preserving meat, which is also used as a folk medicine for centuries. In this study, a water-soluble nonstarch polysaccharide from RYRP was extracted by using ultrasonic-assisted extraction method. By using the Box-Behnken design to optimize the parameters for extracting the RYRP, the maximum extraction yield (3.37 ± 0.78%) was obtained under the optimal extraction conditions as follows: ratio of water to raw material (40 mL/g), extraction temperature (62 °C), extraction time (75 Min), and ultrasonic power (200 W). Moreover, monosaccharide composition analysis showed that RYRP was consisted of mannose, glucosamine, glucose, and galactose with a molar ratio of 0.152:0.015:1:0.149. The molecular weight distribution analysis showed that the average molecular weight of the RYRP fraction was about 3.49 × 103 Da. Furthermore, RYRP exhibited significant antioxidant activities in vitro and the gastrointestinal-protective effect in vivo using gastrointestinal disorders model mice. RYRP could be explored as a potential source in the pharmaceutical and functional food industries.

Mechanisms of Parenteral Nutrition-Associated Liver and Gut Injury.

Parenteral nutrition (PN) has revolutionized the care of patients with intestinal failure by providing nutrition intravenously. Worldwide, PN remains a standard tool of nutrition delivery in neonatal, pediatric, and adult patients. Though the benefits are evident, patients receiving PN can suffer serious cholestasis due to lack of enteral feeding and sometimes have fatal complications from liver injury and gut atrophy, including PN-associated liver disease or intestinal failure-associated liver disease. Recent studies into gut-systemic cross talk via the bile acid-regulated farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) axis, gut microbial control of the TGR5-glucagon-like peptide (GLP) axis, sepsis, and role of prematurity of hepatobiliary receptors are greatly broadening our understanding of PN-associated injury. It has also been shown that the composition of ω-6/ω-3 polyunsaturated fatty acids given parenterally as lipid emulsions can variably drive damage to hepatocytes and cell integrity. This manuscript reviews the mechanisms for the multifactorial pathogenesis of liver disease and gut injury with PN and discusses novel ameliorative strategies.

[From human pluripotent stem cells to custom-made intestinal organoids]. / Organoïdes (2) - Façonner l'intestin à partir des cellules souches pluripotentes humaines.

The study of gut diseases is often limited by the access to human biological tissues and animal models that do not faithfully mimic the human pathologies. In this context, the development of intestinal organoids from human pluripotent stem cells is paving the way of gastrointestinal physiology and digestive disease study. In this review, we recall the embryonic development of the digestive tract and its translation to human pluripotent stem cell differentiation. We also present the different types of intestinal organoids that can be generated, as well as their applications in research.

TITLE: Façonner l'intestin à partir des cellules souches pluripotentes humaines. ABSTRACT: L'étude des maladies digestives est parfois limitée par l'accès aux tissus de patients et les modèles précliniques ne sont pas toujours fidèles aux pathologies observées chez l'homme. Dans ce contexte, le développement d'organoïdes intestinaux à partir de cellules souches pluripotentes humaines représente une avancée importante dans l'étude des processus physiologiques et des pathologies digestives. Dans cette revue, nous rappelons les étapes majeures du développement du tractus digestif chez l'homme et décrivons le rationnel de la différenciation dirigée des cellules souches pluripotentes humaines. Nous faisons également un état des lieux sur les différents types d'organoïdes intestinaux existants et leurs applications en recherche fondamentale et préclinique. Enfin, nous discutons des opportunités offertes par les organoïdes intestinaux humains dans un contexte de médecine de précision et de médecine réparatrice.

Pharmacodynamic interaction of 3α-hydroxymasticadienonic acid and diligustilide against indomethacin-induced gastric damage in rats.

The aims of the study were to evaluate the pharmacodynamic interaction between 3α-hydroxymasticadienonic acid and diligustilide (DLG), isolated from the plants Amphiptherygium adstringens and Ligusticum porteri, respectively, using the indomethacin-induced gastric injury model, as well as their individual gastroprotective efficacy in this model. Male Wistar rats were orally administered with 3α-hydroxymasticadienonic acid, DLG or the mixture of 3α-hydroxymasticadienonic acid-DLG (at a fixed-ratio combination of 1:1, 1:3, and 3:1). Thirty minutes later, the gastric damage was induced by a single oral dose of indomethacin (30 mg/kg). Three hours later, the gastric injury (mm2 ) was determined. 3α-hydroxymasticadienonic acid and DLG as individual compounds showed a gastroprotective effect against indomethacin-induced gastric damage (p < .05). The effective dose (ED50 ) values for each compound were 6.96 ± 1.25 mg/kg for 3α-hydroxymasticadienonic acid and 2.63 ± 0.37 mg/kg for DLG. The isobolographic analysis performed showed that the combination exhibited super-additive interaction as the experimental ED50 values (Zexp) were lower than theoretical additive dose values (Zadd; p < .05). Our results identify the super-additive (synergist) interaction between 3α-hydroxymasticadienonic acid and DLG and the gastric safety of both compounds in the indomethacin-induced gastric injury model, suggesting their potential in the future as a strategy to decrease the gastric damage associated to the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs).

Design and implementation of novel nutraceuticals and derivatives for treating intestinal disorders.

Gastrointestinal illnesses pose a significant worldwide disease burden and are associated with an array of medicinal and surgical therapies. Standard pharmaceutical options have adverse effects, prompting the rise of nutraceutical or food-derivative therapies. Here, we present an overview of the current nutraceutical therapies in gastrointestinal disease. We then introduce the calcium-sensing receptor (CaSR) as a novel therapeutic target. A G-protein-coupled receptor found in apical and basal intestinal cells, the CaSR modulates intestinal fluid secretion and mucosal integrity. Applying nutraceuticals that upregulate the CaSR may alleviate symptoms seen across a spectrum of illnesses. At last, we discuss how nanoparticle technology can be implemented to effectively deliver nutraceuticals to diseased regions of the intestine, thereby minimizing systemic side effects.

Fructus Gardeniae-induced gastrointestinal injury was associated with the inflammatory response mediated by the disturbance of vitamin B6, phenylalanine, arachidonic acid, taurine and hypotaurine metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Gardenia (FG) is a widely used bitter and cold herb for clearing heat and detoxicating. Currently, toxicity of FG and its relative formula has been reported in many clinical and animal studies. However, no systematic research has been carried out on FG-related gastrointestinal (GI) injury which has been emphasized in China since the Ming Dynasty. AIM OF THE STUDY: The purpose of this article is to investigate whether FG could damage GI and explore the mechanisms involved. MATERIAL AND METHODS: FG was given to male mice by 7-day intragastric administration at average doses of 0.90 g (L group), 1.50 g (M group), and 3.00 g (H group) crude drug/kg FG. Comprehensive understanding of changes in weight, diarrhea degree, stool routine, histomorphology and inflammatory factors of stomach, small intestine, and colon for evaluating the effect of different doses of FG on GI injury. Moreover, metabolomics-based mechanisms exploration of FG on GI injury was carried out via HPLC-Q-TOF/MS analysis on mice urine. RESULTS: High dose FG caused GI injury with serious diarrhea, decreased weight, abnormal stool routine, sever alteration in histomorphology of small intestine and colon (mild change in stomach), and significant change in inflammatory factors. The results of metabolomics suggested that 55 endogenous metabolites dispersed in 21 significantly altered metabolic pathways in 3.00 g/kg crude FG treated mice. The hub metabolites of GI injury were mainly related with vitamin B6 metabolism, phenylalanine metabolism, arachidonic acid metabolism, and taurine and hypotaurine metabolism via correlated network analysis. CONCLUSION: FG affected the normal functions of GI via the regulating a variety of metabolic pathways to an abnormal state, and our results provided a research paradigm for the GI-injury of the relative bitter and cold traditional Chinese medicines.

Effect of Rhubarb on Gastrointestinal Dysfunction in Critically Ill Patients: A Retrospective Study Based on Propensity Score Matching.

BACKGROUND: Gastrointestinal dysfunction plays a critical role in the prognosis of critically ill patients. Previous studies showed rhubarb, a traditional Chinese herb, can protect the intestinal barrier function, prevent intestinal bacterial translocation, and promote gastrointestinal peristalsis, but the clinical studies are less. The aim of this study was to evaluate the effects of rhubarb on gastrointestinal dysfunction in critically ill patients. METHODS: From June 2015 to May 2017, a total of 368 critically ill patients with Grade I-III acute gastrointestinal injury (AGI) were enrolled in this study. Patients were divided into two groups according to the exposure factors (whether the patients received rhubarb treatment): the rhubarb group and the usual treatment group. Clinical data were collected within the first 24 h of the Intensive Care Unit (ICU) admission and 7 days after treatment. Survival data on day 28 after ICU admission and the durations of ICU and total hospitalization were also collected. Propensity score matching (PSM) was conducted to reduce confounding bias between the groups. The logistic regression was conducted to screen the influence factors. RESULTS: The eligible patients were divided into rhubarb group (n = 219, 59.5%) and usual treatment group (n = 149, 40.5%). Before PSM, the remission rate of feeding intolerance in rhubarb group and usual treatment group were 59.8% and 39.6%, respectively. After PSM, the remission rate of feeding intolerance in rhubarb group and usual treatment group was 77.9% and 30.9%, respectively. The remission rates of feeding intolerance in rhubarb group were significantly higher than those in the usual treatment group (all P < 0.05). Compared with the usual treatment group, the rhubarb group had a higher rate of AGI improvement, lower level of C-reactive protein, shorter stay in ICU before and after PSM (P < 0.05). There was no significant difference in 28-day mortality between rhubarb and usual treatment groups before and after PSM (48 vs. 33, P = 0.959; and 16 vs. 21, P = 0.335). The logistic regression analysis showed that the single factor, whether receiving rhubarb therapy, affected the proportion of patients whose enteral nutrition needs ≥83.7 kJ·kg-1·d-1 after 7 days of treatment (odds ratio: 7.908, 95% confidence interval: 3.661-17.083, P < 0.001). No serious adverse effects were found in two groups. CONCLUSIONS: The rhubarb might significantly improve feeding tolerance and relieve gastrointestinal dysfunction in critically ill patients, without serious adverse reactions. It provided proof for the treatment of gastrointestinal dysfunction with rhubarb during clinical practice.

Overcoming the exacerbating effects of ranitidine on NSAID-induced small intestinal toxicity with quercetin: Providing a complete GI solution.

There is a need to find/discover novel leads to treat complex and/or multi-factorial-pathogenic disease(s) like Nonsteroidal anti-inflammatory drugs (NSAID)-induced gastroenteropathy or gastrointestinal (GI) toxicity as it has emerged as an important medical and socioeconomic problem. There is no approved therapeutic strategy to prevent NSAID-induced enteropathic damage and highly effective gastro-protective drugs such as ranitidine hydrochloride (RAN) exacerbate it. In this purview, the multi target drug discovery approach (MTDD), combination approach and hit to lead strategies based on the foundation of ethnopharmacology and/or reverse pharmacology holds strong potential. Hence, the primary objectives of the current study were to explore the mechanism behind the preventative/curative effects of quercetin (QCT) on RAN exacerbated diclofenac sodium (DIC)-induced enteropathic damage and to assess the effects of co-administration of QCT and RAN on DIC-induced gastropathic damage in rats. Rats were treated twice daily with QCT (35, 50 and 100 mg kg-1 PO) and/or RAN (15 mg kg-1 PO) or vehicle for a total of 10 days. In some experiments, DIC (9 mg kg-1) was administered orally twice daily for the final 5 days of RAN/QCT + RAN/vehicle administration. Rats in all the groups were fasted after the last dose on 9th day (free access to water). 12 h after the last dose on 10th day, rats were euthanized and their GI tracts were assessed for haemorrhagic damage, alteration in xanthine oxidase (XO) activity, lipid peroxidation, intestinal permeability and GI luminal pH alterations along with haematological and biochemical estimations. The macroscopic, haematological, biochemical and histological evidences suggested that, though, RAN prevented the DIC-induced gastric injury, it exacerbated enteropathic damage. However, QCT not only significantly attenuated the RAN-induced exacerbation of enteropathic damage caused by DIC at the doses of 50 and 100 mg kg-1, but, this combination provided complete GI safety against the toxic effects of DIC too. The mechanisms behind the gastro-enteroprotective ability of QCT may be related to its ability to inhibit XO activity thus, preventing enhanced oxidative stress on GI tissues, prevent lipid peroxidation, IP alteration and alteration in GI luminal pH. The preventative effects of QCT on NSAID-induced gastroenteropathy were ably supported by the QCT induced prevention of GI blood loss and serum protein loss. These pharmaco-mechanistic results of QCT are aligning to combination based MTDD approach and hence we propose it as a promising lead to treat NSAID-gastroenteropahty and related complications.

Ethno-veterinary practices in Southern India for captive Asian elephant ailments.

ETHENOPHARMACOLOGICAL RELEVANCE: India has a long tradition of practicing Ayurvedic medicine not only for human ailments, but also for the management of livestock in the form of ethno-veterinary practices. Asian elephant is a significant part of Indian culture, and ethno-veterinary practices have extended to manage and cure various ailments of Asian elephant in captivity. Much of this knowledge has been lost in the light of modern practices. AIM OF THE STUDY: This study is aimed at documenting the existing knowledge on ethno-veterinary medicines practiced by elephant keepers (mahouts) in Tamil Nadu and Puducherry. MATERIALS AND METHODS: The study was carried out between June 2015 and February 2016 employing a questionnaire survey among 50 selected informants (mahouts) with traditional knowledge on plants in veterinary medicine. Information was elicited from the informants on various diseases prevailing among captive elephants and the traditional treatment employed by them. RESULTS: In total, the study documented 53 plant species belonging to 29 families being used as medicine for 23 types of ailments prevailing among captive elephants. Ferula assa-foetida, Zingiber officinale, Piper longum, P. nigrum, Cuminum cyminum, Trachyspermum roxburghianum and Carum bulbocastanum were the most commonly used plants either independently or in combination. Among them, Ferula assa-foetida (12.4%) and Zingiber officinale (10.4%) had the highest usage. Of the 23 diseases reported, constipation was the most common ailment (14.6%) followed by bloating (8.7%) and flatulence (8.7%). CONCLUSION: Documentation of this indigenous knowledge is valuable for the communities concerned, both at present and in future and for scientific consideration for wider use of traditional knowledge in treating captive elephants. The study has identified 53 medicinal plants to treat various ailments among captive elephants in southern India. The most frequently used plants in the captive elephant health care practice are F. assafoetida, Z. officinale, P. longum and P.nigrum. Among the 29 families, Apiaceae and Piperaceae are widely used. The leaves are the most useful part of the plants, while paste is the widely used form of preparation. The present findings show that mahouts have wide knowledge about elephant diseases and their treatment using herbal medicine. A more detailed investigation should be designed on priority to document the dying art of ethno-veterinary practices for the long-term conservation of the Asian elephant.