Chronic stress is linked to liver injury by increasing intestinal permeability to lipopolysaccharide (LPS), which in turn can result in systemic and liver inflammation and damage. Beneficial effect of honey in the prevention of liver injury has been shown in previous studies, but mechanisms underlying are still less known. Here, we examined the therapeutic impacts of honey on intestinal nuclear factor-κB (NF-κB; an important regulator of stress-induced immune and inflammatory responses) and ileal tight junction (TJ) proteins of claudin-1 and ZO-1, serum LPS, liver inflammation and oxidative markers of malondialdehyde (MDA), nitric oxide (NO), (erythroid-derived 2)-like 2 (Nrf2), tumor necrosis factor (TNF)-α and total antioxidant capacity (TAC) following chronic unpredictable mild stress (CUMS) using Western blotting, ELISA kit and spectrophotometry. Male rats were subjected to CUMS for 28 consecutive days. Honey (0.2 and 2 g/kg/day, by gavage) was administered pretreatment (10 days) and during stress. Honey reduced stress-induced LPS elevation by preventing reduction in the intestinal TJ proteins of claudin-1 and ZO-1, while did not affect NF-kB levels. In liver, honey significantly suppressed stress-induced increase in MDA, NO, TNF-α and Nrf2 expression and normalized TAC. Noteworthy, honey high-dose provoked a greater decrease in TNF-α, Nrf2 and LPS levels than honey low-dose. Together, our study indicated that honey protects against stress-induced liver damage by modulating at least two pathways; intestinal barrier protection via increased TJ protein complex expression, and hepatic TAC protection that may be involved in the inhibition of MDA, NO, TNF-α and Nrf2 expression.
Keywords: Hepatic injury; Honey; Intestinal TJ proteins; Intestinal permeability; LPS; NF-kB; Nrf2; TNF-α.