Enhancing intestinal tight junction assembly by gallic acid as a subcellular basis for the pharmacological effect of Ocimum sanctum L. flower aqueous extract

Abstract

Intestinal tight junction disruption initiates pathogenesis of colitis and determines diseases progression. At present, there is no therapeutics that directly corrects intestinal tight junction disassembly. Here, we discovered that Ocimum sanctum L. flower aqueous extract (OSLF) and gallic acid, increased intestinal barrier function by suppressing tight junction-dependent leak pathway permeability after being disrupted by Ca2+ depletion method. Transepithelial electrical resistance (TER) measurement, western blot analysis, immunofluorescence staining, and molecular docking indicated that OSLF and gallic acid improved intestinal barrier function by inducing tight junction assembly and inhibiting leak pathway permeability in intestinal epithelial cell monolayers via CaMKK-β/AMPK/SIRT-1/ERK-dependent fashion. Therefore, Gallic acid represents a drug candidate for treating diseases associated impaired intestinal barrier function including colitis.