A polysaccharide extract from the medicinal plant Maidong inhibits the IKK–NF-kB pathway and IL-1b–induced islet inflammation and increases insulin secretion

Abstract

The herb dwarf lilyturf tuber (Maidong, Ophiopogonis Radix) is widely used in Chinese traditional medicine to manage diabetes and its complications. However, the role of Maidong polysaccharide extract (MPE) in pancreatic b-cell function is unclear. Here, we investigated whether MPE protects b-cell function and studied the underlying mechanisms. We treated db/db and high-fat diet (HFD)-induced obese mice with 800 or 400 mg/kg MPE or water for 4 weeks, followed by an oral glucose tolerance test. Pancreas and blood were collected for molecular analyses, and clonal MIN6 b-cells and primary islets from HFD-induced obese mice and normal chow diet–fed mice were used in additional analyses. In vivo, MPE both increased insulin secretion and reduced blood glucose in the db/db mice but increased only insulin secretion in the HFD-induced obese mice. MPE substantially increased the b-cell area in both models (3-fold and 2-fold, p < 0.01, for db/db and HFD mice, respectively). We observed reduced nuclear translocation of the p65 subunit of NF-kB in islets of MPE-treated db/db mice, coinciding with enhanced glucose-stimulated insulin secretion (GSIS). In vitro, MPE potentiated GSIS and decreased interleukin 1b (IL-1b) secretion in MIN6 b-cells. Incubation of MIN6 cells with tumor necrosis factor a (TNFa), interferon-g, and IL-1b amplified IL-1b secretion and inhibited GSIS. These effects were partially reversed with MPE or the IkB kinase b inhibitor PS1145, coinciding with reduced activation of p65 and p-IkB in the NF-kB pathway. We conclude that MPE may have potential for therapeutic development for b-cell protection.