Improving the Effects of Mulberry Leaves and Neochlorogenic Acid on Glucotoxicity-Induced Hepatic Steatosis in High Fat Diet Treated db/db Mice

Abstract

There are many complications of type 2 diabetes mellitus. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are two complications related to the increased lipid accumulation in the liver. Previous studies have shown that mulberry leaf water extract (MLE) has the effect of lowering lipid levels in peripheral blood, inhibiting the expression of fatty acid synthase (FASN) and increasing the activity of liver antioxidant enzymes superoxide dismutase (SOD) and catalase. Our study aimed to investigate the role of MLE and its main component, neochlorogenic acid (nCGA), in reducing serum lipid profiles, decreasing lipid deposition in the liver, and improving steatohepatitis levels. We evaluated the antioxidant activity including glutathione (GSH), glutathione reductase (GRd), glutathione peroxidase (GPx), glutathione S-transferase (GST), and superoxide dismutase (SOD), and catalase was tested in mice fed with MLE and nCGA. The results showed a serum lipid profile, and fatty liver scores were significantly increased in the HFD group compared to the db/m and db mice groups, while liver antioxidant activity significantly decreased in the HFD group. When fed with HFD + MLE or nCGA, there was a significant improvement in serum lipid profiles, liver fatty deposition conditions, steatohepatitis levels, and liver antioxidant activity compared to the HFD group. Although MLE and nCGA do not directly affect the blood sugar level of db/db mice, they do regulate abnormalities in lipid metabolism. These results demonstrate the potential of MLE/nCGA as a treatment against glucotoxicity-induced diabetic fatty liver disease in animal models.

Keywords: antioxidant activities; diabetes mellites; mulberry leaves; neochlorogenic acid; nonalcoholic fatty liver disease.

Figure 1

MLE reduction of hepatic steatosis in HFD-induced diabetic mice. Six-week-old male db/db mice fed with HFD and MLE for 12 weeks. Liver frozen sections were stained using H&E (A) and Oil red O (B). The arrow indicates the presence of polymorphonuclear leukocytes. The experimental groups consisted of age-matched heterozygous mice assigned to the normal diet group (db/m), db/db mice divided into two groups (normal diet group (db) and high-fat diet group (HFD)), and a group of db/db mice fed HFD and administered MLE (MLE).

Figure 2

nCGA reduction of hepatic steatosis in HFD-induced diabetic mice. Six-week-old male db/db mice fed with HFD and MLE for 12 weeks. Liver frozen sections were stained using H&E (A) and Oil red O (B). The arrow indicates the presence of polymorphonuclear leukocytes. The experimental groups consisted of age-matched heterozygous mice assigned to the normal diet group (db/m), db/db mice divided into two groups (normal diet group (db) and high-fat diet group (HFD)), and a group of db/db mice fed HFD and administered nCGA (nCGA).