Enhancing intestinal tight junction assembly by gallic acid as a subcellular basis for the pharmacological effect of Ocimum sanctum L. flower aqueous extract
Wanapas Wachiradejkul, Pichayapa Sukmak, Supisara Treveeravoot, Laphatrada Yurasakpong, Nutnicha Rangchaikul, Pimngeon Chatkul, Pitsinee Supapol, Apiwan Arinno, Natnicha Teansuk, Jakkapong Inchai, Sukpaporn Phummisutthigoon, Makha Phongjit, Autsadakorn Loungjan, Nattaphong Akrimajirachoote, Wanangkan Poolsri, Chanat Aonbangkhen, Rungtiwa Khumjiang, Chatchai Muanprasat, Chutima S. Vaddhanaphuti, Pawin Pongkorpsakol
Abstract
• OSLF promotes intestinal barrier function and tight junction-dependent leak pathway permeability. • Gallic acid is a major chemical component of OSLF and exerts the pharmacological effect of OSLF. • Gallic acid and OSLF enhances ZO-1 and occludin recovery to cell junction via CaMKK-β/AMPK/SIRT-1/ERK-dependent mechanism. • Gallic acid represents a drug candidate for treating diseases associated impaired intestinal barrier function. 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 Ca 2+ 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.