Tannic acid acts as an agonist of the dopamine D2L receptor, regulates immune responses, and ameliorates experimentally induced colitis in mice.

Tannic acid (TA) is an herbal polyphenol containing a galloyl group that has been prescribed to treat gastroenteritis, diarrhea, and irritable bowel syndrome. TA has anti-inflammatory, anti-cancer, and anti-viral properties; however, the molecular mechanisms of these potential therapeutic effects are still largely unknown. Here, we examined the ability of TA to induce anti-inflammatory responses. TA was found to be an agonist of the dopamine D2L receptor. TA reduced interferon (IFN)-γ and interleukin (IL)-1β secretion but upregulated tumor necrosis factor α and IL-10 secretion from lipopolysaccharide (LPS)-stimulated mouse splenocytes. TA also reduced IFN-γ secretion but enhanced IL-10 secretion from anti-cluster of differentiation (CD) 3/CD28 antibody-stimulated splenocytes. An immune subset study confirmed that TA regulated cytokine secretion by various types of immune cells in the context of stimulation with LPS or anti-CD3/CD28 antibodies. Administration of TA to mice with experimentally induced colitis strikingly suppressed weight loss, colon shrinkage, and IL-17 secretion from mesenteric lymph node lymphocytes in response to CD3/CD28 stimulation. These data suggest that TA suppresses inflammatory responses in colitis by regulating cytokine secretion by immune cells in the colon.