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Hepatoprotective effects of zingerone on carbon tetrachloride- and dimethylnitrosamine-induced liver injuries in rats

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Abstract

In this study, we investigated the hepatoprotective and anti-fibrotic effects of zingerone, one of the active components of ginger, against carbon tetrachloride (CCl4)- and dimethylnitrosamine (DMN)-induced liver injuries in rats, respectively. Oral administration of zingerone (10 mg/kg) reduced CCl4-induced abnormalities in liver histology, serum alanine aminotransferase and aspartate aminotransferase levels, and liver malondialdehyde levels. Zingerone treatment attenuated CCl4-induced increases in inflammatory mediators, including tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and inducible nitric oxide synthase mRNA levels. Western blot analysis showed that zingerone suppressed activation of nuclear factor-kappa B (NF-κB) p65 and phosphorylation of extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinases (MAPKs). Liver fibrosis induced by DMN (10 mg/kg, intraperitoneally) was ameliorated by administration of zingerone (10 and 20 mg/kg, orally). Zingerone treatment reduced DMN-induced elevation of hydroxyproline content and hepatic stellate cell activation. In conclusion, zingerone showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream MAPKs. Moreover, zingerone had hepatoprotective and anti-fibrotic effects against DMN-induced liver injury suggesting its usefulness in the prevention of liver inflammation and the development of hepatic fibrosis.

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Acknowledgments

This work was supported by a 2-year Research Grant of Pusan National University. We thank the Aging Tissue Bank (Busan, Korea) for supplying research materials.

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Correspondence to Jeon-Ok Moon.

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Cheong, K.O., Shin, DS., Bak, J. et al. Hepatoprotective effects of zingerone on carbon tetrachloride- and dimethylnitrosamine-induced liver injuries in rats. Arch. Pharm. Res. 39, 279–291 (2016). https://doi.org/10.1007/s12272-015-0696-2

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  • DOI: https://doi.org/10.1007/s12272-015-0696-2

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