Abstract
Background2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is an active compound derived from Polygonum multiflorum Thunb., a Chinese Taoist herbal medicine, which exerts lipid lowering, anti-cancer, anti-aging, anti-inflammatory and hepatoprotective effects. However, its role in protecting hepatocytes under pre-diabetic condition remains unclear.MethodsIn this study, we developed prediabetic SD rats by feeding high-fat and high-sugar diet. The body weight, blood lipid, blood glucose, and fasting insulin (FINS) and insulin resistance index (HOMA-IR) were detected and calculated to assess the potential risk of prediabetes. HE and Oil Red O staining was used, and blood level of biochemical index was detected to observe the liver injury. The autophagic cell death-associated signaling proteins, and the potential signaling factors p-Akt/Akt and p-Erk/Erk were detected using western blot to explore the potential effects of TSG on pre-diabetic liver and the underlying mechanisms.ResultsThe results showed that the body weight in TSG-treated group was significantly decreased vs. the model group. The blood glucose, the level of FINS and HOMA-IR, TC and TG were decreased in TSG-treated group as well. Furthermore, TSG treatment significantly ameliorated lipid droplet accumulation, enhanced liver anti-oxidative response which may be associated with an increased activity of SOD and GSH-Px, and a decrease of LDLC and MDA. The autophagic cell death-associated proteins, p-AMPK, ATG12, LC3 II, and Beclin 1 were up-regulated in the TSG-treated group, while the upstream signaling pathway, PI3K/Akt and Erk, were activated.ConclusionsTSG induced liver autophagic cell death to protect liver from prediabetic injury by activating PI3K/Akt and Erk.Graphical abstract
Highlights
Diabetes mellitus (DM) is a metabolic disorder with high blood glucose level and the patients suffer from symptoms of frequent urination, severe thirst and increased appetite
TSG reversed the increase of body weight, blood glucose, and the level of fasting insulin (FINS) and Insulin resistance index (HOMA-IR) As shown in Fig. 2, the body weight, fasting plasma glucose (FPG) and Two-hour postprandial blood glucose (2hPBG), FINS and HOMA-IR were increased in Model group vs. control group (Ctrl) group, indicating high-fat and -sucrose feeding increased body weight and blood glucose in the prediabetic rats
TSG reversed the increased level of body weight, FPG, 2hPBG, FINS and HOMA-IR, indicating TSG attenuated the prediabetic condition in the rats as compared to Model group
Summary
Diabetes mellitus (DM) is a metabolic disorder with high blood glucose level and the patients suffer from symptoms of frequent urination, severe thirst and increased appetite. Among all types of DM, type 2 DM (T2DM) is associated with unhealthy lifestyles such as lack of physical exercise, consumption of high-fat and high-sugar food [1]. Terrible chronic complications include visual impairment, cardiovascular disease, stroke, diabetic ketoacidosis, hyperosmolar hyperglycemic state, or even death. The initiation of T2DM may encounter the process of prediabetes. World Health Organization (WHO) defined the condition of intermediate hyperglycemia, which did not go on to develop diabetes, as socalled prediabetes [2]. It was estimated that the overall prevalence of prediabetes was up to 35.7% in China in 2013 [3]. The prediabetes was defined as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT)
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