Protective Effect of Hawthorn Fruit Extract against High Fructose-Induced Oxidative Stress and Endoplasmic Reticulum Stress in Pancreatic β-Cells

Abstract

Hyperglycemia has deleterious effects on pancreatic β-cells, causing dysfunction and insulin resistance that lead to diabetes mellitus (DM). The possible causes of injury can be caused by glucose- or fructose-induced oxidative and endoplasmic reticulum (ER) stress. Hawthorn (Crataegus pinnatifida) fruit has been widely used as a hypolipidemic agent in traditional herbal medicine. The study aimed to investigate whether high fructose-induced pancreatic β-cell dysfunction could be reversed through amelioration of ER stress by the treatment of polyphenol-enriched extract (PEHE) from hawthorn fruit. The extract was partitioned using ethyl acetate as a solvent from crude water extract (WE) of hawthorn fruits, followed by column fractionation. The results showed that the contents of total polyphenols, flavonoids and triterpenoids in PEHE could be enhanced by 2.2-, 7.7- and 1.1-fold, respectively, in comparison to the original obtained WE from hawthorn fruit. In ER stress studies, a sharp increase in the inhibitory activity on the gene expression levels of GRP79, ATF6, IRE1α and CHOP involved in ER stress was evident when dosages of PEHE at 50–100 μg/mL were used against high-fructose (150 mM)-treated cells. HPLC–MS/MS analysis showed that polyphenols and flavonoids collectively accounted for 87.03% of the total content of PEHE.

Keywords

• hawthorn fruit
• <i>Crataegus pinnatifida</i>
• polyphenol-enriched extract
• pancreatic β-cell
• hyperglycemia
• endoplasmic reticulum (ER) stress