The Potentials of Curcumin and Tetrahydrocurcumin in Hepatic Lipid and Glucose Metabolism Related Diabetes Mellitus and Non-Alcoholic Fatty Liver Diseases
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Abstract
The Liver is a crucial organ to metabolize endogenous substances, dietary, or xenobiotics in the body. Several diseases such as diabetes mellitus (DM) and non-alcoholic fatty liver disease (NAFLD) associated with deterioration of hepatic glucose and lipid metabolism. Turmeric or Curcuma longa is a herbal plant commonly used as a spice and a traditional medicine. The main yellow active compounds of turmeric is curcumin, in which tetrahydrocurcumin (THC) is its active colorless metabolite. The protective effect of both compounds related to lipid and glucose metabolism were presented in both DM and NAFLD. In In vitro anti-diabetic mechanism model, curcumin activated AMP-activated protein kinase (AMPK) and suppressed effect on gluconeogenic gene expression such as phosphoenol pyruvate carboxy kinase (PEPCK) and glucose 6-phosphatase (G6Pase) in hepatoma cells. Turmeric extract with main active constituents, i.e., curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone, suppressed an increase of blood glucose level in the KK-Ay mice. THC was reported to reduce plasma glucose, insulin, haemoglobin, and glycosylated haemoglobin (HbA1c) in the type 2-DM rats with lowering lipid and lipoprotein profiles, and improving HDL cholesterol in the streptozotocin-nicotinamide-induced diabetic rats. Down-regulation of HMG-CoA reductase activity in hypercholesterol treated rats by THC was also reported. Curcumin supplementation lowered lipid and lipoprotein cholesterol levels, and improved apolipoprotein profiles in the high fat-fed hamsters. Curcumin increased hepatic lipid–regulating enzyme activity such as fatty acid β-oxidation was noted. Turmeric extract decreased cholesterol synthesis and increased cholesterol conversion into bile acid in the hypercholestrolemic rats via down-regulation of HMG-CoA reductase expression and up-regulation of cholesterol 7α-hydroxylase (CYP7A1) and LDL receptor, resulting in lowering plasma cholesterol level. Though, curcumin and THC have exhibited positive effects on DM and NAFLD, an evidence supporting mechanism to delay progression or manage these diseases is still incomplete. Hence, further studies is required for clarify a key regulatory mechanism for the use of these two compounds in the liver related diseases.
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