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Glycyrrhizin ameliorates metabolic syndrome-induced liver damage in experimental rat model

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Abstract

Glycyrrhizin, a major constituent of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate insulin resistance, hyperglycemia, dyslipidemia, and obesity in rats with metabolic syndrome. Liver dysfunction is associated with this syndrome. The objective of this study is to investigate the effect of glycyrrhizin treatment on metabolic syndrome-induced liver damage. After induction of metabolic syndrome in rats by high fructose (60 %) diet for 6 weeks, the rats were treated with glycyrrhizin (50 mg/kg body weight, single intra-peritoneal injection). After 2 weeks of treatment, rats were sacrificed to collect blood samples and liver tissues. Compared to normal, elevated activities of serum alanine transaminase, alkaline phosphatase and aspartate transaminase, increased levels of liver advanced glycation end products, reactive oxygen species, lipid peroxidation, protein carbonyl, protein kinase Cα, NADPH oxidase-2, and decreased glutathione cycle components established liver damage and oxidative stress in fructose-fed rats. Activation of nuclear factor κB, mitogen-activated protein kinase pathways as well as signals from mitochondria were found to be involved in liver cell apoptosis. Increased levels of cyclooxygenase-2, tumor necrosis factor, and interleukin-12 proteins suggested hepatic inflammation. Metabolic syndrome caused hepatic DNA damage and poly-ADP ribose polymerase cleavage. Fluorescence-activated cell sorting using annexin V/propidium iodide staining confirmed the apoptotic hepatic cell death. Histology of liver tissue also supported the experimental findings. Treatment with glycyrrhizin reduced oxidative stress, hepatic inflammation, and apoptotic cell death in fructose-fed rats. The results suggest that glycyrrhizin possesses therapeutic potential against hepatocellular damage in metabolic syndrome.

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Acknowledgments

R. S received research fellowship from University Grants Commission (UGC), India. D. R received research fellowship from Council of Scientific and Industrial Research (CSIR), India. Assistances from the Departmental Special Assistance Programme of UGC and Centre for Research in Nanoscience and Nanotechnology (CRNN), University of Calcutta are gratefully acknowledged.

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  1. Doel Ray

    Present address: School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, 110067, India

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  1. Department of Biophysics, Molecular Biology and Bioinformatics, University College of Science, University of Calcutta, 92 Acharyya Prafulla Chandra Road, Kolkata, West Bengal, 700009, India

    Rajarshi Sil, Doel Ray & Abhay Sankar Chakraborti

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Sil, R., Ray, D. & Chakraborti, A.S. Glycyrrhizin ameliorates metabolic syndrome-induced liver damage in experimental rat model. Mol Cell Biochem 409, 177–189 (2015). https://doi.org/10.1007/s11010-015-2523-y

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