Aims Oxidative stress and inflammation are always associated. Appropriate management of oxidative mediators may represent a therapeutic strategy to reduce inflammation, and use of antioxidant can be protective against inflammatory diseases. Glycyrrhizin (GL) plays an anti-inflammatory and antioxidant effect by inhibiting high mobility group box 1 (HMGB1) or 11-β-hydroxysteroid dehydrogenase type II (11βHSD2) enzyme. In this study, the potential role of dipotassium glycyrrhizate (DPG), a salt of GL, to reduce oxidative stress in intestinal inflammatory condition was investigated in vivo and the mechanism of action of DPG was studied in vitro. Results In a colitis mouse model DPG affected oxidative stress reducing iNOS and COX-2 expression, as well as NO and PGE2 levels. By means of LPS-stimulated macrophages we found that DPG inhibited the expression of pro-inflammatory cytokines and reduced iNOS and COX-2 expression in a time dependent manner, through two different ways of signal. DPG reduced, at a later time, both iNOS and COX-2, through a mechanism HMGB1-dependent, and at an earlier time only COX-2, through a mechanism AMP-activated kinase (AMPK)-phosphorylation-mediated. Conclusion DPG has a protective effect on colitis and inflammation through the inhibition of oxidative stress. This study clarifies the two-ways mechanism by which DPG inhibits iNOS and COX-2 during inflammation and demonstrates for the first time that AMPK is a target of DPG. Uncovering this mechanism is significant to clarify the relationship between energy homeostasis and anti-oxidative responses and suggests that DPG could play a relevant role in the development of new therapy against inflammatory diseases associated to oxidative stress.
All Science Journal Classification (ASJC) codes
Vitali, R., Palone, F., Pierdomenico, M., Negroni, A., Cucchiara, S., Aloi, M., ... Stronati, L. (2015). Dipotassium glycyrrhizate via HMGB1 or AMPK signaling suppresses oxidative stress during intestinal inflammation. Biochemical Pharmacology, 97(3), 292 - 299. https://doi.org/10.1016/j.bcp.2015.07.039