Treatment with oligonol, a low-molecular polyphenol derived from lychee fruit, attenuates diabetes-induced hepatic damage through regulation of oxidative stress and lipid metabolism

Abstract

We have identified the effects of oligonol, a low-molecular polyphenol derived from lychee fruit, on oxidative stress and lipid metabolism in a type 2 diabetic model. Oligonol was orally administered at 10 or 20 mg per kg body weight per d for 8 weeks to db/db mice, and its effects were compared with those of the vehicle in db/db and m/m mice. Serum and hepatic biochemical factors, and protein and mRNA expression related to lipid metabolism were measured. In the oligonol-administered group, there were significant reductions of reactive oxygen species (ROS), lipid peroxidation, and the TAG and total cholesterol concentrations in both the serum and liver. Additionally, oligonol attenuated oxidative stress through the inhibition of advanced glycation endproduct formation and its receptor expression. Furthermore, augmented expressions of NF-kBp65 and inducible NO synthase were down-regulated to the levels of m/m mice in the group treated with oligonol at 20 mg/kg. Regarding lipid metabolism, lower hepatic lipid resulted from the down-regulation of sterol regulatory element-binding protein-1 and its target gene of lipogenic enzymes in the liver of db/db mice. The present results suggest that oligonol has protective effects against ROS-related inflammation and excess lipid deposition in the type 2 diabetic liver.Key words: Oligonol: Type 2 diabetes: Oxidative stress: Dyslipidaemia: Steatosis Type 2 diabetes is associated with oxidative stress and abnormal lipid metabolism due to hyperglycaemia and hyperlipidaemia. Increased reactive oxygen species (ROS) generation and lipid peroxidation activate stress-sensitive intracellular signalling pathways such as the transcription of NF-kB, which plays a central role in inflammation-related disease (1) . In addition, hyperglycaemia accelerates the formation of advanced glycation endproducts (AGE), which are proteins produced from non-enzymic glycation reactions (2) . AGE and their binding with receptors, such as the receptor for AGE (RAGE), galectin-3 and CD36, induce free radical formation. They accumulate during the normal ageing process and at accelerated rates during the course of diabetes, and are associated with the pathogenesis of chronic diseases such as arthritis, atherosclerosis, liver cirrhosis and diabetic nephropathy (3) . Therefore, the attenuation of oxidative stress during the initiation and propagation of type 2 diabetes is important to prevent a vicious cycle of inflammatory responses and tissue damage. Moreover, insulin resistance in type 2 diabetes leads to a marked disruption of lipid dynamics, often reflected by elevated levels of circulating NEFA and TAG, together with excess fat deposition in various tissues (4) . Lipid homeostasis is regulated by a transcription factor, sterol regulatory elementbinding protein (SREBP), which is highly expressed in the presence of metabolic disorders such as obesity and diabetes. In particular, up-regulated SREBP-1 has been suggested to play a central role in the development of hepatic steatosis in an insulin-res...

Oligonol Attenuates Diabetes-Induced Pancreatic Damage by Inhibiting Inflammatory Responses via Oxidative Stress-Dependent MAPK/NF-kB Signaling

“…To avoid any intergroup differences in these indices, the rats were divided into three experimental groups: group 1, diabetic rats receiving water (n=5); groups 2 and 3, diabetic rats receiving 10 or 20 mg/kg body weight/day of oligonol (n=5, each group) through once-daily oral gavage. The administration dose and duration were determined based on other reports [12][13][14]. Rats that underwent a sham injection of citrate buffer without STZ were used as a nondiabetic control group (n=5).…”

“…Kundu et al [10] reported the beneficial antioxidant and anti-inflammatory effects of oligonol in mouse skin, while Ahn et al [11] showed that oligonol protects against oxidative stress-induced inflammation in C6 glial cells. In our previous studies, oligonol improved hyperglycemia and hyperglycemia-induced oxidative stress in the liver and kidney of type 2 diabetic db/db mice, attenuated renal damage through the inhibition of glycation end product formation by glucose accumulation, and subsequently decreased NAD(P)H oxidase-derived ROS production in the kidney of db/db mice [12][13][14]. Therefore, oligonol appears to represent a novel therapeutic approach to a range of conditions associated with diabetes and hyperglycemia-related disorders such as oxidative stress and inflammation; however, the details of the mechanisms are still unknown.…”

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“…Oligonol is a patented, low-molecular-weight polyphenol derived from lychee fruit (85%) and green tea (15% In another study carried out by Noh and group found that treatment of Oligonol(10 or 20 mg/kg) for 8 weeks to db/db mice reducedthe level of reactive oxygen species (ROS), lipid peroxidation, and the TAG and total cholesterol concentrations in both the serum and liver and attenuated oxidative stress through the inhibition of advanced glycation endproduct formation and its receptor expression 43 .…”

Development and significance of RAPD-SCAR markers for the identification of Litchi chinensis Sonn. by improved RAPD amplification and molecular cloning

“…Litchi is an edible fruit and is used in traditional medicine. As a traditional medicine, the fruit and its secondary metabolic products have been reported to have anticancer, anti-inflammatory, antifungal, antiviral, antioxidant, antiplatelet and anticoagulant, and antidiabetic activities [5,6,7,8,9,10,11,12].…”