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Cytoprotective effects of xanthohumol against methylglyoxal‐induced cytotoxicity in MC3T3‐E1 osteoblastic cells
Author(s) -
Suh Kwang Sik,
Chon Suk,
Choi Eun Mi
Publication year - 2018
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3521
Subject(s) - xanthohumol , methylglyoxal , chemistry , pharmacology , glutathione , cytotoxicity , reactive oxygen species , biochemistry , oxidative stress , glycation , superoxide dismutase , lactoylglutathione lyase , viability assay , apoptosis , biology , enzyme , in vitro , key (lock) , ecology , receptor
Methylglyoxal (MG) has been suggested to be a major source of intracellular reactive carbonyl compounds, and has been implicated in increasing the levels of advanced glycation end products in age‐related diseases. Xanthohumol is a prenylated flavonoid found in hops ( Humulus lupulus ) and beer. In the present study, we investigated the effects of xanthohumol on MG‐induced cytotoxicity in osteoblastic MC3T3‐E1 cells. Xanthohumol attenuated MG‐induced cytotoxicity, as evidenced by improved cell viability, and prevented MG‐induced MG‐protein adducts, inflammatory cytokines, reactive oxygen species and mitochondrial superoxide production. In addition, xanthohumol increased glyoxalase I activity, glutathione, heme oxygenase‐1 and nuclear factor erythroid 2‐related factor 2 levels in the presence of MG. Pretreatment with xanthohumol before MG exposure reduced MG‐induced mitochondrial dysfunction. Furthermore, xanthohumol treatment resulted in a significant reduction in the levels of endoplasmic reticulum stress and autophagy induced by MG. Notably, the autophagy‐reducing effect of xanthohumol was abolished after the addition of Ex527, a selective inhibitor of sirtuin 1, suggesting that xanthohumol is an effective sirtuin 1 activator for reducing autophagy. Taken together, our findings suggest xanthohumol as a promising new strategy for preventing diabetic osteopathy.