Therapeutic Potential of Ruberythric Acid in Intestinal Inflammation and Barrier Function Reduction

Inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract, which results from pathogen-activated inflammatory mechanisms, and is increasingly prevalent worldwide, warranting further research. Ruberythric acid (RBA), a major polyphenolic compound of the anthraquinone family, is abundantly present in the roots of Rubia cordifolia L., which has traditionally been used for the treatment of coughs and skin diseases. However, its effects and mechanisms in IBD prevention remain unclear. Therefore, this study aimed to determine whether RBA alleviates inflammatory mechanisms and affects the tight junction protein localization. We evaluated the effect of RBA based on changes in the intestinal permeability in Caco-2 cells. RBA significantly inhibited the lipopolysaccharide (LPS)- and tumor necrosis factor (TNF)-α-induced increases in intestinal permeability in a dose-dependent manner. In addition, it substantially attenuated the LPS- and TNF-α-induced localization of tight junction proteins at a concentration of 50 μM. Furthermore, RBA significantly inhibited the redistribution of tight junctions by activating the nuclear factor-kappa B (NF-κB)-myosin light-chain kinase signaling pathway. This study indicates that RBA regulates tight junction protein localization and intestinal permeability by modulating the NF-κB pathway, thereby suggesting its potential as a nutraceutical for treating IBD.