curcumin and Diarrhea

Tube feeding (TF) is the most common form of nutrition support. In recent years, TF administration has increased among patient populations within and outside hospital settings, in part due to greater insurance coverage, reduced use of parenteral nutrition, and improved formularies suitable for sole source nutrition. With increasing life expectancy and improved access to TFs, the number of adults dependent on enteral nutrition is expected to grow. However, enteral TF intolerance (ETFI) is the most common complication of TFs, typically presenting with at least 1 adverse gastrointestinal event, including nausea, diarrhea, and constipation. ETFI often leads to reductions in TF volume with associated energy and protein deficits. Potentially ensuing malnutrition is a major public health concern due its effects on increased risk of morbidity and mortality, infections, prolonged hospital length of stay, and higher healthcare costs. As such, there is a need for intervention strategies to prevent and reduce ETFI. Incorporating whole foods with bioactive properties is a promising strategy. Emerging research has elucidated bioactive properties of whole foods with specific benefits for the prevention and management of adverse gastrointestinal events commonly associated with TFs. However, lack of evidence-based recommendations and technological challenges have limited the use of such foods in commercial TF formulas. This review addresses research gaps by discussing 5 whole foods (rhubarb, banana, curcumin, peppermint oil, and ginger) with bioactive attributes identified through literature searches and clinical experience as having substantial scientific rationale to consider their application for ETFI in adult populations.

Topics: Adult; Constipation; Curcumin; Diarrhea; Enteral Nutrition; Food, Formulated; Humans; Malnutrition; Mentha piperita; Musa; Nausea; Plant Oils; Plants, Edible; Rheum; Zingiber officinale

This study was conducted to characterize the effects of feeding 3 plant extracts on gene expression in ileal mucosa of weaned pigs. Weaned pigs (n = 32, 6.3 ± 0.2 kg BW, and 21 d old) were housed in individual pens for 9 d and fed 4 different diets: a nursery basal diet as control diet, basal diet supplemented with 10 mg/kg of capsicum oleoresin, garlic botanical, or turmeric oleoresin. Results reported elsewhere showed that the plant extracts reduced diarrhea and increased growth rate of weaning pigs. Total RNA (4 pigs/treatment) was extracted from ileal mucosa of pigs at d 9. Double-stranded cDNA was amplified, labeled, and further hybridized to the microarray. Microarray data were analyzed in R using packages from the Bioconductor project. Differential gene expression was tested by fitting a mixed linear model equivalent to ANOVA using the limma package. Bioinformatics analysis was conducted by DAVID Bioinformatics Resources. Three pairwise comparisons were used to compare each plant extract diet with the control diet. Quantitative real time PCR was applied to verify the mRNA expression detected by microarray. Compared with the control diet, feeding capsicum oleoresin altered (P < 0.05) the expression of 490 genes (280 up, 210 down), and feeding garlic botanical altered (P < 0.05) the expression of 64 genes (33 up, 31 down), while feeding turmeric oleoresin altered (P < 0.05) the expression of 327 genes (232 up, 95 down). Compared with the control diet, feeding capsicum oleoresin and turmeric oleoresin increased [Expression Analysis Systematic Explorer (EASE) < 0.05] the expression of genes related to integrity of membranes and tight junctions, indicating enhanced gut mucosa health, but decreased (EASE < 0.05) the cell cycle pathway. Feeding each of the 3 plant extracts enhanced (EASE < 0.05) the expression of genes associated with immune responses, indicating that feeding these plant extracts may stimulate the immune responses of pigs in the normal conditions. In conclusion, plant extracts regulated the expression of genes in ileal mucosa of pigs, perhaps providing benefits by enhancing the gut mucosa health and stimulating the immune system.

Topics: Animals; Curcuma; Diarrhea; Dietary Supplements; Garlic; Gene Expression Regulation; Intestinal Mucosa; Microarray Analysis; Plant Extracts; Sus scrofa; Swine; Transcriptome

Since the improvement of chemotherapy with safe molecules is needed for a better efficacy without supplementary toxicity, we investigated the feasibility and tolerability of the combination of docetaxel and curcumin, a polyphenolic derivative extracted from Curcuma longa root.. Fourteen patients were accrued in this open-label phase I trial. At the last dose level of curcumin, three dose-limiting toxicities were observed and two out of three patients at this dose level refused to continue treatment, leading us to define the maximal tolerated dose of curcumin at 8,000 mg/d. Eight patients out of 14 had measurable lesions according to RECIST criteria, with five PR and three SD. Some improvements as biological and clinical responses were observed in most patients.. Patients with advanced or metastatic breast cancer were eligible. Docetaxel (100 mg/m(2)) was administered as a 1 h i.v. infusion every 3 w on d 1 for six cycles. Curcumin was orally given from 500 mg/d for seven consecutive d by cycle (from d-4 to d+2) and escalated until a dose-limiting toxicity should occur. The primary endpoint of this study was to determine the maximal tolerated dose of the combination of dose-escalating curcumin and standard dose of docetaxel chemotherapy in advanced and metastatic breast cancer patients. Secondary objectives included toxicity, safety, vascular endothelial growth factor and tumor markers measurements and assessment of objective and clinical responses to the combination therapy.. The recommended dose of curcumin is 6,000 mg/d for seven consecutive d every 3 w in combination with a standard dose of docetaxel. From the encouraging efficacy results, a comparative phase II trial of this regimen plus docetaxel versus docetaxel alone is ongoing in advanced and metastatic breast cancer patients.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Breast Neoplasms, Male; Carcinoma; Curcumin; Diarrhea; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Feasibility Studies; Female; Follow-Up Studies; Humans; Leukopenia; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neutropenia; Taxoids; Time Factors; Treatment Outcome

To assess the effects of turmeric (Curcuma longa) extract on irritable bowel syndrome (IBS) symptomology in otherwise healthy adults.. Partially blinded, randomized, two-dose, pilot study.. Five hundred (500) volunteers were screened for IBS using the Rome II criteria. Two hundred and seven (207) suitable volunteers were randomized.. One or two tablets of a standardized turmeric extract taken daily for 8 weeks.. IBS prevalence, symptom-related quality of life (IBSQOL) and self-reported effectiveness.. IBS prevalence decreased significantly in both groups between screening and baseline (41% and 57%), with a further significant drop of 53% and 60% between baseline and after treatment, in the one- and two-tablet groups respectively (p < 0.001). A post-study analysis revealed abdominal pain/discomfort score reduced significantly by 22% and 25% in the one- and two-tablet group respectively, the difference tending toward significance (p = 0.071). There were significant improvements in all bar one of the IBSQOL scales of between 5% and 36% in both groups, approximately two thirds of all subjects reported an improvement in symptoms after treatment, and there was a favorable shift in self-reported bowel pattern. There were no significant differences between groups.. Turmeric may help reduce IBS symptomology. Placebo controlled trials are now warranted to confirm these findings.

Topics: Abdominal Pain; Aged; Curcuma; Diarrhea; Dose-Response Relationship, Drug; Female; Gastrointestinal Agents; Humans; Irritable Bowel Syndrome; Male; Middle Aged; Pilot Projects; Plant Extracts; Severity of Illness Index; Single-Blind Method; Time Factors; Treatment Outcome

Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent colon cancer in rodents. In view of the sparse information on the pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation pilot study of a novel standardized Curcuma extract in proprietary capsule form was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of curcumin. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies received Curcuma extract daily for up to 4 months. Activity of glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, were measured in patients' blood cells. Oral Curcuma extract was well tolerated, and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites were detected in blood or urine, but curcumin was recovered from feces. Curcumin sulfate was identified in the feces of one patient. Ingestion of 440 mg of Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic glutathione S-transferase activity. At higher dose levels, this effect was not observed. Leukocytic M(1)G levels were constant within each patient and unaffected by treatment. Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment. The results suggest that (a) Curcuma extract can be administered safely to patients at doses of up to 2.2 g daily, equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in humans and may undergo intestinal metabolism; and (c) larger clinical trials of Curcuma extract are merited.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Agents; CA-19-9 Antigen; Carcinoembryonic Antigen; Colorectal Neoplasms; Curcumin; Diarrhea; Dose-Response Relationship, Drug; Female; Glutathione Transferase; Humans; Lymphocytes; Male; Middle Aged; Nausea; Pilot Projects; Plant Extracts; Polymorphism, Genetic; Treatment Outcome

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that causes lethal watery diarrhea in neonatal pigs and poses economic and public health burdens. Currently, there are no effective antiviral agents against PDCoV. Curcumin is the active ingredient extracted from the rhizome of turmeric, which has a potential pharmacological value because it exhibits antiviral properties against several viruses. Here, we described the antiviral effect of curcumin against PDCoV. At first, the potential relationships between the active ingredients and the diarrhea-related targets were predicted through a network pharmacology analysis. Twenty-three nodes and 38 edges were obtained using a PPI analysis of eight compound-targets. The action target genes were closely related to the inflammatory and immune related signaling pathways, such as the TNF signaling pathway, Jak-STAT signaling pathway, and so on. Moreover, IL-6, NR3C2, BCHE and PTGS2 were identified as the most likely targets of curcumin by binding energy and 3D protein-ligand complex analysis. Furthermore, curcumin inhibited PDCoV replication in LLC-PK1 cells at the time of infection in a dose-dependent way. In poly (I:C) pretreated LLC-PK1 cells, PDCoV reduced IFN-β production via the RIG-I pathway to evade the host's antiviral innate immune response. Meanwhile, curcumin inhibited PDCoV-induced IFN-β secretion by inhibiting the RIG-I pathway and reduced inflammation by inhibiting IRF3 or NF-κB protein expression. Our study provides a potential strategy for the use of curcumin in preventing diarrhea caused by PDCoV in piglets.

Topics: Animals; Antiviral Agents; Coronavirus; Curcumin; Diarrhea; LLC-PK1 Cells; Swine; Swine Diseases

Diarrheal shellfish toxins (DSTs) are among the most widely distributed phytotoxins, and are associated with diarrheal shellfish poisoning (DSP) events in human beings all over the world. Therefore, it is urgent and necessary to identify an effective method for toxin removal in bivalves. In this paper, we found that curcumin (CUR), a phytopolylphenol pigment, can inhibit the accumulation of DSTs (okadaic acid-eq) in the digestive gland of

Topics: Animals; Curcumin; Diarrhea; Humans; Inactivation, Metabolic; Marine Toxins; Okadaic Acid; Perna; Shellfish Poisoning

Irinotecan (CPT‑11) is a DNA topoisomerase I inhibitor which is widely used in clinical chemotherapy, particularly for colorectal cancer treatment. However, late‑onset diarrhea is one of the severe side‑effects of this drug and this restricts its clinical application. The present study aimed to investigate the protective effects of curcumin treatment on CPT‑11‑induced intestinal mucosal injury both in vitro and in vivo and to elucidate the related mechanisms involved in these effects. For this purpose, mice were intraperitoneally injected with CPT‑11 (75 mg/kg) for 4 days to establish a model of late‑onset diarrhea. Curcumin (100 mg/kg) was intragastrically administered 8 days before the injection of CPT‑11. Injury to small intestinal tissues was examined by H&E staining. The protein expression of prolyl 4‑hydroxylase subunit beta (P4HB) and peroxiredoxin 4 (PRDX4) was detected by immunohistochemistry, as well as western blot analysis. IEC‑6 cell viability was detected by MTT assay. Flow cytometry was performed to examine the cell apoptotic rate, mitochondrial membrane potential and reactive oxygen species (ROS) generation. Immunofluorescence was used to observe the localization of nuclear factor (NF)‑κB. The levels of cleaved caspase‑3, glucose‑regulated protein, 78 kDa (GRP78), P4HB, PRDX4 and CHOP were detected by western blot analysis. The results revealed that in vivo, curcumin effectively attenuated the symptoms of diarrhea and abnormal intestinal mucosa structure induced by CPT‑11 in nude mice. Treatment with curcumin also increased the expression of P4HB and PRDX4 in the tissue of the small intestine. In vitro, curcumin, exhibited little cytotoxicity when used at concentrations <2.5 µg/ml for 24 h in IEC‑6 cells. At this concentration, curcumin also improved cell morphology, inhibited apoptosis, maintained mitochondrial membrane potential and reduced the elevated levels of ROS induced by CPT‑11 (20 µg/ml). Furthermore, curcumin abolished NF‑κB signal transduction and protected the cells from CPT‑11‑induced apoptosis by upregulating the expression of molecular chaperones, such as GRP78, P4HB and PRDX4, and suppressing the levels of the apoptosis‑related proteins, CHOP and cleaved caspase‑3. On the whole, our data indicate that curcumin exerted protective effects against CPT‑11‑induced intestinal mucosa injury. The protective effects of curcumin are mediated by inhibiting the activation of NF‑κB, and suppressing oxidative stress and endoplasmic reti

Topics: Animals; Apoptosis; Cell Line; Colorectal Neoplasms; Curcumin; Diarrhea; Disease Models, Animal; Drug Evaluation, Preclinical; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Epithelial Cells; Humans; Injections, Intraperitoneal; Intestinal Mucosa; Irinotecan; Male; Mice; Mice, Inbred BALB C; Mice, Nude; NF-kappa B; Oxidative Stress; Rats; Signal Transduction; Topoisomerase I Inhibitors; Treatment Outcome

Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is a lethal autoimmune disease caused by mutations in the Foxp3 gene scurfin (scurfy). Immunosuppressive therapy for IPEX patients has been generally ineffective and has caused severe side effects, however curcumin has shown immune regulation properties for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases without side effects.. The aim of this study was to investigate whether curcumin would attenuate symptoms of IPEX in mouse model and would prolong its survival period.. C57BL/6 mice were separated into scurfy or wild-type litter mate groups by genotyping, and each group subsequently was separated into 2 subgroups that were fed a 1% curcumin containing or normal diet from the last day of breast-feeding. After weaning, pups were fed either a 1% curcumin containing or normal diet until all scurfy mice die for survival data. To elucidate immune cell proportions in spleen and lymph nodes, cells were analyzed by flowcytometry. Cellular cytokine production was accessed to investigate the effects of curcumin in T cell differentiation in vitro.. Scurfy mice fed a 1% curcumin diet survived 4.0-fold longer compared to scurfy (92.5 days) mice fed a normal diet (23 days). A curcumin diet decreased all of the Th1/Th2/Th17 cell populations and attenuated diverse symptoms such as splenomegaly in scurfy mice. In vitro experiments showed that curcumin treatment directly decreased the Th1/Th2/Th17 cytokine production of IFN-γ, IL-4, and IL-17A in CD4. Curcumin diet attenuated the scurfy-induced immune disorder, a model of IPEX syndrome, by inhibiting Th1/Th2/Th17 responses in mice. These results have implications for improving clinical therapy for patients with IPEX and other T cell related autoimmune diseases.

Topics: Animals; Autoimmune Diseases; Curcumin; Diabetes Mellitus, Type 1; Diarrhea; Diet; Disease Models, Animal; Genetic Diseases, X-Linked; Immune System Diseases; Interleukin-17; Interleukin-4; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Th1 Cells; Th17 Cells; Th2 Cells

The compound 5-fluorouracil (5-FU) is used in cancer chemotherapy and is known to cause diarrhoea. We recently reported that chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophils in the colonic mucosa were markedly increased by the administration of 5-FU in mice. Curcumin has anti-inflammatory, antitumour and antioxidant properties. Therefore, we examined the effect of curcumin on 5-FU-induced diarrhoea development and CXCL1 and CXCL2 up-regulation in the colon. Mice were given 5-FU (50 mg/kg, i.p.) daily for 4 days. Curcumin (100 or 300 mg/kg, p.o.) was administered on the day before the first administration of 5-FU and administered 30 min. before the administration of 5-FU. Gene expression levels of CXCL1 and CXCL2 in the colon were examined by real-time RT-PCR. Curcumin reduced the 5-FU-induced diarrhoea development. Under this condition, the CXCL1 and CXCL2 gene up-regulated by 5-FU administration was inhibited by curcumin. The gene expression of CXCL1 and CXCL2 was also enhanced by 5-FU application in vitro. The 5-FU-induced up-regulated CXCL1 and CXCL2 gene expressions were inhibited by curcumin, Bay-117082 and bortezomib, nuclear factor kappa B (NF-κB) inhibitors, C646, a p300/cyclic adenosine monophosphate response element-binding protein-histone acetyltransferase (HAT) inhibitor. In conclusion, these findings suggested that curcumin prevented the development of diarrhoea by inhibiting NF-κB and HAT activation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites, Antineoplastic; Antioxidants; Chemokine CXCL1; Chemokine CXCL2; Colon, Descending; Curcumin; Diarrhea; Dietary Supplements; E1A-Associated p300 Protein; Enzyme Inhibitors; Fluorouracil; Gene Expression Regulation; Intestinal Mucosa; Male; Mice, Inbred C57BL; NF-kappa B; Severity of Illness Index; Tissue Culture Techniques

Curcumin is the organic extract of turmeric and possesses known anti-inflammatory properties. Our aim was to explore the utility of curcumin in patients with HIV-associated diarrhea. Eight patients with HIV-associated diarrhea were given a mean daily dose of 1,862 mg of curcumin and followed for a mean of 41 weeks. All had resolution of diarrhea and normalization of stool quality in a mean time of 13 +/- 9.3 days. Mean number of bowel movements per day dropped from 7 +/- 3.6 to 1.7 +/- 0.5. Seven of eight patients had considerable weight gain on curcumin (10.8 +/- 8.9 lbs). Five of six patients had resolution of bloating and abdominal pain. Patients on anti-retroviral therapy experienced no discernible drug interactions, changes in CD(4) count, or changes in HIV viral load while taking curcumin. Curcumin therapy was associated with rapid and complete resolution of diarrhea, substantial weight gain, improvement in the reduction of bloating and abdominal pain.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Retroviral Agents; CD4 Lymphocyte Count; Curcumin; Diarrhea; Drug Interactions; HIV Enteropathy; Humans; Male; Middle Aged; Treatment Outcome; Weight Gain