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

Abstract

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.

Fructo‐oligofructose ameliorates 2,4‐dinitrofluorobenzene‐induced atopic dermatitis‐like skin lesions and psychiatric comorbidities in mice

“…[46][47][48] It has been reported that administering dopamine or activating dopamine D2L receptors could reduce secretion of IFN-γ. 49,50 Our results are consistent with this, as a correlation analysis showed that IFN-γ was negatively correlated with dopamine (r = −0.981). Stimulation of dopamine D3 receptors (D3R) reduced mast cell activation and inhibited IL-13 release in the mouse gut, which correlated significantly and negatively with the results of our correlation analysis between DA in brain and IL-13 in skin (P < 0.05, r = −0.960).…”

Ropinirole inhibits inflammatory cytokine production in gingival epithelial cells and suppresses alveolar bone loss in an experimental rat model of periodontitis

“…We also showed previously that tannic acid is a D2-like receptor agonist, and that tannic acid suppressed IL-17 production in chemically induced colitis models (19). More recently, we determined that tannic acid inhibited alveolar bone resorption in a carrageenan-induced rat model of periodontitis (20).…”

Hydrolysable tannins as a potential therapeutic drug for the human fibrosis‐associated disease

“…HT have been shown to contribute to declining of ROS formation, suppressing the nuclear factor kappa‐B (NF‐κB) pathway, and inhibiting the expression of proinflammatory mediators by immune cells in multiple disease models of mice induced by lipopolysaccharide (LPS). These disease models include neuroinflammation, colitis, depressive‐like behaviors, acute lung injury, and septic heart injury (Kawano et al, 2020; Luduvico et al, 2020; Sivanantham, Pattarayan, Rajasekar, et al, 2019). In vitro studies also suggested that HT mainly alleviated inflammatory response by reducing the inflammatory cytokines and inhibiting ROS production in cells (Wu et al, 2019; Yang et al, 2021).…”