Effects of ε‐viniferin, a dehydrodimer of resveratrol, on transepithelial active ion transport and ion permeability in the rat small and large intestinal mucosa

ε‐Viniferin is a dehydrodimer of resveratrol, a polyphenol synthesized in many plants, including grapevine. The present study investigated the effects of ε‐viniferin and resveratrol on epithelial secretory and barrier functions in isolated rat small and large intestinal mucosa. Mucosa–submucosa tissue preparations of various segments of the rat large and small intestines were mounted on Ussing chambers, and short‐circuit current (I (sc)) and tissue conductance (G (t)) were continuously measured. The mucosal addition of ε‐viniferin (>10(−5) mol/L) and resveratrol (>10(−4) mol/L) to the cecal mucosa, which was the most sensitive region, induced an increase in I (sc) and a rapid phase decrease (P‐1) followed by rapid (P‐2) and broad (P‐3) peak increases in G (t) in concentration‐dependent manners. Mucosal ε‐viniferin (10(−4) mol/L), but not resveratrol (10(−4) mol/L), increased the permeability of FITC‐conjugated dextran (4 kDa). The mucosal ε‐viniferin–evoked changes in I (sc) (Cl(−) secretion), but not in G (t), were attenuated by a selective cyclooxygenase (COX)‐1 inhibitor and a selective EP (4) prostaglandin receptor. The mucosal ε‐viniferin–evoked increase in I (sc) was partially attenuated, and P‐2, but not P‐1 or P‐3, change in G (t) was abolished by a transient receptor potential cation channel, subfamily A, member 1 (TRPA1) inhibitor. Moreover, the mucosal ε‐viniferin concentration‐dependently attenuated the mucosal propionate (1 mmol/L)‐evoked increases in I (sc) and G (t). Immunohistochemical studies revealed COX‐1–immunoreactive epithelial cells in the cecal crypt. The present study showed that mucosal ε‐viniferin modulated transepithelial ion transport and permeability, possibly by activating sensory epithelial cells expressing COX‐1 and TRPA1. Moreover, mucosal ε‐viniferin decreased mucosal sensitivity to other luminal molecules such as short‐chain fatty acids. In conclusion, these results suggest that ε‐viniferin modifies intestinal mucosal transport and barrier functions.