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  1. Cheng HS, Kong JM, Ng AX, Chan WK, Ton SH, Abdul Kadir K
    Nat Prod Bioprospect, 2014 Dec;4(6):325-33.
    PMID: 25369772 DOI: 10.1007/s13659-014-0044-0
    Beneficial effects of glycyrrhizic acid (GA), a bioactive extract of licorice root, in the prevention of metabolic syndrome have been consistently reported while advanced glycation end products (AGE) and receptor for advanced glycation end product (RAGE) are the leading factors in the development of diabetes mellitus. The aim of this study was to investigate the effects of GA on the AGE-RAGE axis using high-fat/high-sucrose (HF/HS) diet-induced metabolic syndrome rat models. Twenty four male Sprague-Dawley rats were randomly assigned into three groups for 4 weeks: (1) Group A, normal diet with standard rat chow; (2) Group B, HF/HS diet; (3) Group C, HF/HS diet and oral administration of 100 mg/kg GA per day. The results showed that HF/HS diet elevated the fasting blood glucose level and insulin resistance index which was prevented by GA supplementation. GA treatment significantly lowered the circulating AGE independent of its glucose-lowering effect. HF/HS diet also triggered RAGE upregulation in the abdominal muscles while GA administration downregulated RAGE expression in the abdominal muscles, aorta and subcutaneous adipose tissues. In conclusion, HF/HS diet could cause glucose intolerance, insulin resistance and upregulation of RAGE expression while GA ameliorated the metabolic dysregulation besides exhibiting inhibitory effects on the AGE-RAGE axis.
  2. Cheng HS, Yaw HP, Ton SH, Choy SM, Kong JM, Abdul Kadir K
    Nutrition, 2016 Sep;32(9):995-1001.
    PMID: 27130470 DOI: 10.1016/j.nut.2016.02.002
    OBJECTIVE: To investigate the effects of glycyrrhizic acid supplementation on glucose and lipid metabolism in rodents consuming a high-fat, high-sucrose diet.

    METHODS: Twenty-four male, 8-week old Sprague Dawley rats with an initial weight of 160 to 200 g were randomised into three groups (n = 6 for each group): groups A (standard rat chow), B (high-fat, high-sucrose diet), and C (high-fat, high-sucrose diet + 100 mg/kg/d of glycyrrhizic acid via oral administration). The rats were treated accordingly for 4 wk. Glycaemic parameters, lipid profile, stress hormones, and adiponectin levels were measured after the treatment. Relative gene expressions of peroxisome proliferator-activated receptor α and γ, lipoprotein lipase as well as gluconeogenic enzymatic activities in different tissues were also determined.

    RESULTS: Consumption of high-fat, high-sucrose diet triggered hyperglycaemia, insulin resistance, and dyslipidemia, which were effectively attenuated by supplementation with glycyrrhizic acid. Glycyrrhizic acid supplementation also effectively reduced circulating adrenaline, alleviated gluconeogenic enzymes overactivity, and promoted the upregulation of lipoprotein lipase expression in the cardiomyocytes and skeletal muscles. A high calorie diet also triggered hypoadiponectinaemia and suppression of peroxisome proliferator-activated receptor γ expression, which did not improve with glycyrrhizic acid treatment.

    CONCLUSION: Supplementation with glycyrrhizic acid could alleviate high calorie diet-induced glucose and lipid metabolic dysregulations by reducing circulatory stress hormones, normalizing gluconeogenic enzyme activities, and elevating muscular lipid uptake. The beneficial effects of these bioactivities outweighed the adverse effects caused by diet-induced repression of peroxisome proliferator-activated receptor γ expression, resulting in the maintenance of lipid and glucose homeostasis.

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