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J Appl Toxicol. 2018 Feb;38(2):180-192. doi: 10.1002/jat.3521. Epub 2017 Sep 20.

Cytoprotective effects of xanthohumol against methylglyoxal-induced cytotoxicity in MC3T3-E1 osteoblastic cells.

Author information

1
Department of Endocrinology & Metabolism, School of Medicine, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul, 02447, Republic of Korea.

Abstract

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.

KEYWORDS:

cytotoxicity; methylglyoxal; mitochondrial function; osteoblasts; xanthohumol

PMID:
28940469
DOI:
10.1002/jat.3521
[Indexed for MEDLINE]

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