Protective effect of acorn (Quercus liaotungensis Koidz) on streptozotocin-damaged MIN6 cells and type 2 diabetic rats via p38 MAPK/Nrf2/HO-1 pathway

Ethnopharmacological relevance: Acorn obtained from the Quercus liaotungensis Koidz tree is consumed as a Chinese folk medicine for the treatment of diarrhea, abdominal pain, and inflammation, also having strong antioxidant activity and have been utilized for the treatment of diabetes in China. However, its mechanism of action on complications of diabetes and oxidative stress is unclear.

Aim of the study: The purpose of this research was to assess the effects of acorn (Quercus liaotungensis Koidz) ethanol extract (AE) on pancreatic β-cell dysfunction through a streptozotocin (STZ)-damaged mouse normal pancreatic β-cell (MIN6 cell) model in vitro, and by using a high-fat and high-sugar diet with STZ-induced diabetic rat model in vivo to explore the possible mechanism of action against diabetes.

Materials and methods: MIN6 cells were pretreated with AE (20, 40, 80 μM) for 2 h and then treated with 3 mM STZ for 24 h. Cell viability was measured by MTT assay. The amount of intracellular reactive oxygen species was measured by 2,7-dichlorodi-hydrofluorescein diacetate. The activities of insulin secretion, superoxide dismutase, catalase and glutathione were determined by kits. Sprague Dawley rats were either given normal feed or a high sugar and fat diet for four weeks, followed STZ (25 mg/kg, via i. p.) was given. Rats with fasting blood glucose ≥ 11.1 mmol/l after one week were deemed to be diabetic. Animals were divided into 5 groups, which received saline (10 mL/kg), metformin (200 mg/kg), or AE at doses of 200 and 400 mg/kg during 4 weeks by oral gavage. Blood samples were used to evaluate hematological and biochemical indicators, and pancreas was removed for post-analysis. Body weight and fasting blood glucose were recorded weekly. The expression levels of Bax, Bcl-2, p38, p-p38, Nrf2 and HO-1 were determined by western blot.

Results: Data showed that AE inhibited apoptosis and increased antioxidant level in STZ-induced MIN6 cells. In addition, the AE-administered group lowered blood glucose, increased insulin secretion, and alleviated weight loss in the diabetic rats. Histopathologically, the AE-administered group reduced pancreatic injury by significantly restoring the insulin content in β-islets. It was observed that the anti-diabetic effects of AE were associated with the suppressed the p38 MAPK pathway and actived the Nrf2 pathway.

Conclusions: The ameliorative impact of AE on diabetes may be attributed to protection of the function of pancreatic β islets and by improving serum insulin levels, hence reducing the blood glucose, which involved in the p38 MAPK and Nrf2 pathways.

Keywords: Acorn; Diabetes; Insulin secretion; Oxidative stress; Pancreas.