Chronic administration of Angelica sinensis polysaccharide effectively improves fatty liver and glucose homeostasis in high-fat diet-fed mice

Environmental factors, such as a high-fat diet (HFD) and a sedentary lifestyle, are the causes of the current epidemic of metabolic syndrome, which is characterized by a group of metabolic risks including hyperglycemia, hyperlipidemia, hypertension and insulin resistance1. Excessive exposure to a HFD is believed to play a key role in the pathogenesis of metabolic damages and has led to an increased number of individuals with nonalcoholic fatty liver disease (NAFLD) and diabetes2,3. NAFLD, which represents a spectrum of liver pathologies that range from simple steatosis to severe hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, has become the most common cause of chronic liver diseases4. HFD-induced hyperglycemia increases the risk of development of type 2 diabetes, which is also an epidemic disease in modern society. Changes in dietary habits merit particular consideration because a HFD leads to severe hyperglycemia, metabolic damages and fatty liver. However, the modification of dietary habits and lifestyles are not readily accepted in many developed countries. Therefore, dietary supplementation or consumption of health foods could be an alternative means for the prevention of metabolic syndrome. Traditional Chinese medicines are rich sources of bioactive substances that can be used to pretreat or cure various types of human diseases5. Polysaccharides are polymeric carbohydrate macromolecules composed of long chains of monosaccharide units that are connected by various glycosidic linkages. Currently, an increasing number of studies have focused on polysaccharides extracted from different Chinese medicines due to their potential pharmacological activities. Many types of polysaccharides have shown appreciable effects in the amelioration of NAFLD or diabetes, such as Lycium barbarum polysaccharide6, Radix Hedysari polysaccharide7, Aureobasidium pullulans-derived β-glucan8, Rehmannia glutinosa polysaccharide9 and Ganoderma lucidum polysaccharide10. Specifically, these polysaccharides have demonstrated hypolipidemic/hypoglycemic effects or antioxidative properties. Angelica sinensis polysaccharide (ASP), a biomacromolecule isolated from the roots of Angelica sinensis, has drawn accumulating attention recent years for its various bioactivities, such as hematopoietic, immunomodulatory, hepatoprotective, and antioxidant activities, among others11,12,13,14. In addition, our group has demonstrated that ASP has hypoglycemic and hypolipidemic effects in a mouse model of type 2 diabetic mice and that this action was mediated by an elevation of glycogen levels and a reduction of inflammatory factors15. In the current study, we established an HFD-induced mouse model that resulted in fatty liver, hyperglycemia, as well as severe oxidative stress16,17. We then explored the potential effects of ASP on the improvement of metabolic dysfunction and oxidative stress in HFD-fed mice by examining various physiological parameters and investigating the mechanisms underlying these beneficial properties. Our findings demonstrate that ASP is an excellent candidate for the prevention of HFD-induced metabolic syndrome. Therefore, to prevent the NAFLD or diabetes, ASP can be used as a health care product or food supplement in populations that consistently consume HFDs.