Daikenchuto and Processed Ginger Alleviate Liver Ischemia–Reperfusion Injury by Enhancing Anti‐Inflammatory Effects and HO ‐1 Production

ABSTRACT Background and Aim Daikenchuto (DKT), a Kampo medicine, is widely used in surgical practice because of its pro‐motility effects on the gastrointestinal tract. Although its anti‐inflammatory effects in the gastrointestinal tract have been well documented, its role in hepatic ischemia–reperfusion injury (IRI) remains unclear. This study investigated the protective effects of DKT and its individual components against hepatic IRI. Methods Male C57BL/6 mice were fed a diet containing 3.6% DKT or its individual herbal components for 1 week before 60 min of partial hepatic ischemia. Liver injury was evaluated based on serum liver enzyme levels, histology, and TUNEL staining. Portal venous adrenomedullin (ADM) levels and hepatic heme oxygenase‐1 (HO‐1) expression were also assessed. In vitro, peritoneal macrophages were stimulated with High Mobility Group Box 1 (HMGB1) to examine the effects of DKT and 6‐shogaol (6SG). Results DKT significantly reduced serum alanine aminotransferase levels, necrotic area, and hepatocyte apoptosis compared to the control. Although single‐herb doses equivalent to those in the DKT formula did not confer protection, a threefold dose of processed ginger reproduced the hepatoprotective effects of DKT. DKT did not increase portal ADM levels. In contrast, both DKT and 6SG significantly upregulated HO‐1 expression in vivo and suppressed the production of inflammatory cytokines in HMGB1‐stimulated macrophages in vitro. Conclusion DKT attenuates liver IRI via HO‐1 induction and suppression of macrophage‐mediated inflammation, rather than via ADM elevation. These protective effects may be mediated, at least in part, by processed ginger.