Geniposide attenuates dextran sulfate sodium-induced colitis in mice via Nrf-2/HO-1/NF-κB pathway.

Abstract

Geniposide (GE) is the main component in gardenia fruit. This study aimed to investigate the protective effects and potential mechanisms of GE on dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-induced RAW 264.7 cells. The in vivo acute colitis experimental model was established by administering drinking water containing 3% DSS to the mice for 7 days. GE was administered to the mice via oral gavage at 20 and 40 mg/kg for 7 days. Colon length, colon myeloperoxidase (MPO) level, serum and colon malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity were determined, and histological evaluation was performed. The levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) in the serum and colon were detected. The expression of proteins of the nuclear factor E2 related factor 2 (Nrf-2)/HO-1/ NF-κB pathway in the colon was detected. The in vitro model of LPS-induced RAW 264.7 cells to simulate enteritis model. Cell viability, IL-6, IL-1β, and TNF-α levels in the cell supernatant were measured. The MPO levels in RAW 264.7 cells and DSS-induced mice and MDA and SOD levels in the cell supernatant were measured. The expression of proteins of the Nrf-2/HO-1/NF-κB pathway in RAW 264.7 cells was determined. GE treatment resulted in significant histological changes and reduced the expression of inflammatory mediators IL-6, IL-1β, and TNF-α the in serum, colon, and cell supernatant effectively. Parenteral nutrition reduced MPO content in the colon and RAW 264.7 cells. GE treatment increased SOD levels in the serum, colon, and cell supernatant. GE restored the protein expression of the Nrf-2/HO-1/ NF-κB pathway in RAW 264.7 cells and nude mice, and these changes were blocked significantly by Nrf-2 siRNA. These findings demonstrated that GE ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf-2/HO-1/NF-κB pathway. Thus, GE could serve as a potential therapeutic agent for the treatment of ulcerative colitis (UC).