AIM To investigate the therapeutic effect of hydrogen-rich water(HRW) on inflammatory bowel disease(IBD) and to explore the potential mechanisms involved.METHODS Male mice were randomly divided into the following four groups: control group, in which the mice received equivalent volumes of normal saline(NS) intraperitoneally(ip); dextran sulfate sodium(DSS) group, in which the mice received NS ip(5 m L/kg body weight, twice per day at 8 am and 5 pm) for 7 consecutive days after IBD modeling; DSS + HRW group, in which the mice received HRW(in the same volume as the NS treatment) for 7 consecutive days after IBD modeling; and DSS + HRW + Zn PP group, in which the mice received HRW(in the same volume as the NS treatment) and ZnP P [a heme oxygenase-1(HO-1) inhibitor, 25 mg/kg] for 7 consecutive days after IBD modeling. IBD was induced by feeding DSS to the mice, and blood and colon tissues were collected on the 7th d after IBD modeling to determine clinical symptoms, colonic inflammation and the potential mechanisms involved.RESULTS The DSS + HRW group exhibited significantly attenuated weight loss and a lower extent of disease activity index compared with the DSS group on the 7th d(P < 0.05). HRW exerted protective effects against colon shortening and colonic wall thickening in contrast to the DSS group(P < 0.05). The histological study demonstrated milder inflammation in the DSS + HRW group, which was similar to normal inflammatory levels, and the macroscopic and microcosmic damage scores were lower in this group than in the DSS group(P < 0.05). The oxidative stress parameters, including MDA and MPO in the colon, were significantly decreased in the DSS + HRW group compared with the DSS group(P < 0.05). Simultaneously, the protective indicators, superoxide dismutase and glutathione, were markedly increased with the use of HRW. Inflammatory factors were assessed, and the results showed that the DSS + HRW group exhibited significantly reduced levels of TNF-α, IL-6 and IL-1β compared with the DSS group(P < 0.05). In addition, the pivotal proteins involved in endoplasmic reticulum(ER) stress, including p-e IF2α, ATF4, XBP1 s and CHOP, were dramatically reduced after HRW treatment in contrast to the control group(P < 0.05). Furthermore, HRW treatment markedly up-regulated HO-1 expression, and the use of Zn PP obviously reversed the protective role of HRW. In the DSS + HRW + ZnP P group, colon shortening and colonic wall thickening were significantly aggravated, and the macroscopic damage scores were similar to those of the DSS + HRW group(P < 0.05). The histological study also showed more serious colonic damage that was similar to the DSS group.CONCLUSION HRW has a significant therapeutic potential in IBD by inhibiting inflammatory factors, oxidative stress and ER stress and by up-regulating HO-1 expression. AIM To investigate the therapeutic effect of hydrogen-rich water (HRW) on inflammatory bowel disease (IBD) and to explore the potential mechanisms involved. METHODS Male mice were randomly divided into the following four groups: control group, in which the mice received equivalent volumes of normal saline (NS) intraperitoneally (ip); dextran sulfate sodium (DSS) group, where the mice received NS ip (5 m L / kg body weight, twice per day at 8 am and 5 pm) for 7 consecutive days after IBD modeling; DSS + HRW + Zn PP group, where the mice received HRW (in the same volume as the NS treatment) for 7 consecutive days after IBD modeling; the same volume as the NS treatment and ZnP P [a heme oxygenase-1 (HO-1) inhibitor, 25 mg / kg] for 7 consecutive days after IBD modeling. IBD was induced by feeding DSS to the mice, and blood and colon tissues were collected on the 7th day after IBD modeling to determine clinical symptoms, colonic inflammation a nd the potential mechanisms involved .RESULTS The DSS + HRW group showed significant attenuated weight loss and a lower extent of disease activity index compared with the DSS group on the 7th d (P <0.05). HRW exerted protective effects against colon shortening and colonic wall thickening in contrast to the DSS group (P <0.05). The histological study demonstrated milder inflammation in the DSS + HRW group, which was similar to normal inflammatory levels, and the macroscopic and microcosmic damage scores were lower in this group than in the DSS The oxidative stress parameters, including MDA and MPO in the colon, were significantly decreased in the DSS + HRW group compared with the DSS group (P <0.05). Simultaneously, the protective indicators, superoxide dismutase and glutathione , were markedly increased with the use of HRW. Inflammatory factors were assessed, and the results showed that the DSS + HRW group were significantly reduced reduced levels of TNF-α, IL-6 and I LIn addition, the pivotal proteins involved in endoplasmic reticulum (ER) stress, including pe IF2α, ATF4, XBP1 s and CHOP, were dramatically reduced after HRW treatment in contrast to the control group (P <0.05). In addition, HRW treatment markedly up-regulated HO-1 expression, and the use of Zn PP act reversed the protective role of HRW. In the DSS + HRW + ZnP P group, colon shortening and colonic wall thickening were significantly aggravated, and the macroscopic damage scores were similar to those of the DSS + HRW group (P <0.05). The histological study also showed more serious colonic damage that was similar to the DSS group. CONCLUSION HRW has a significant therapeutic potential in IBD by inhibiting inflammatory factors, oxidative stress and ER stress and by up-regulating HO-1 expression.