A Tannic Acid-Based Medical Food, Cesinex®, Exhibits Broad-Spectrum Antidiarrheal Properties: A Mechanistic and Clinical Study

Abstract

Background To evaluate the efficacy and tolerability of a tannic acid-based medical food, Cesinex®, in the treatment of diarrhea, and to investigate the mechanisms underlying its antidiarrheal effect. Methods Cesinex® was prescribed to six children and four adults with diarrhea. Patient records were retrospectively reviewed for the primary outcome. Cesinex® and its major component, tannic acid, were tested for their effects on cholera toxin-induced intestinal fluid secretion in mouse. Polarized human gut epithelial cells (HT29-CL19A cells) were used to investigate the effects of tannic acid on epithelial barrier properties, transepithelial chloride secretion, and cell viability. Results Successful resolution of diarrheal symptoms was reported in nine of ten patients receiving Cesinex®. Treatment of HT29-CL19A cells with clinically relevant concentrations of tannic acid (0.01–1 mg/ml) significantly increased transepithelial resistance and inhibited the CFTR-dependent or the calcium-activated Cl− secretion. Tannic acid could also improve the impaired epithelial barrier function induced by TNFα and inhibited the disrupting effect of TNFα on the epithelial barrier function in these cells. CTX-induced mouse intestinal fluid secretion was significantly reduced by administration of Cesinex® or tannic acid. Cesinex® has high antioxidant capacity. Conclusions Cesinex® demonstrates an effective and safety profile in treatment of diarrhea. The broad-spectrum antidiarrheal effect of Cesinex® can be attributed to a combination of factors: its ability to improve the epithelial barrier properties, to inhibit intestinal fluid secretion, and the high antioxidant property.

Compartmentalized Accumulation of cAMP near Complexes of Multidrug Resistance Protein 4 (MRP4) and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Contributes to Drug-induced Diarrhea

“…Measurement of Intestinal Fluid Secretion in Mice-Intestinal fluid secretion measurement in murine ileal loops was performed as described previously (12). Three ileal loops were made on the ileum between 0.5 and 3.5 cm from the cecum, between the jejunum and the cecum, and each closed loop was injected with PBS-diluted DMSO, 0.5 g of cholera toxin (Sigma-Aldrich), or 4 -100 M irinotecan (Sigma-Aldrich).…”

“…The in Silico Topological Study for Docking of Irinotecan into MRP4 -The three-dimensional structure of MRP4 isoenzymes was constructed by the homology modeling method (12). Each MRP4 isoenzyme sequence was derived from BLAST (blast.…”

“…Ϫ/Ϫ Mice Are Resistant to Irinotecan-induced Fluid Secretion-We evaluated the effect of irinotecan (4 and 50 M) on intestinal fluid secretion in wild-type (Mrp4 ϩ/ϩ ) and Mrp4 Ϫ/Ϫ mice using a closed-loop diarrhea model (12). DMSO (the solvent for irinotecan) was used as a negative control, and cholera toxin (0.5 g/loop), which activates CFTR-mediated fluid secretion, was used as a positive control.…”

Targeting CD38 in the tumor microenvironment; a novel approach to treat glioma

“…TA also has anti-oxidant activity and acts as a scavenger of reactive free radicals [31] . Moreover, a TA-based medical food supplement is currently in clinical trials for the treatment of diarrhea, in which it was demonstrated to be safe and effective [32] .…”

Macromolecular Complexes of Cystic Fibrosis Transmembrane Conductance Regulator Alter Fluid Transport in inflammatory Bowel Disorders

“…Based on the effects of LPA in downregulating CFTR function and ameliorating diarrheal phenotype of CTX-injected mice, an LPA-rich diet can effectively control certain forms of diarrhea. Cesinex®, a tannic acid based medical food is prescribed for diarrheal episodes in USA and could successfully attenuate CTX-induced diarrhea in mice (98). It is known that egg albumen has high amounts of LPA.…”