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A polysaccharide extract from the medicinal plant Maidong inhibits the IKK-NF-kappa B pathway and IL-1 beta-induced islet inflammation and increases insulin secretion

作者 Mao, Dandan; Tian, Xiao Yu; Mao, Di; Hung, Sze Wan; Wang, Chi Chiu; Lau, Clara Bik San; Lee, Heung Man; Wong, Chun Kwok; Chow, Elaine; Ming, Xing; Cao, Huanyi; Ma, Ronald C.; Chan, Paul K. S.; Kong, Alice P. S.; Li, Joshua J. X.; Rutter, Guy A.; Tam, Wing Hung; Chan, Juliana C. N.

期刊 JOURNAL OF BIOLOGICAL CHEMISTRY , SEP 4 2020,36:295

DOI 10.1074/jbc.RA120.014357 PubMed 32605924

摘要 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 beta-cell function is unclear. Here, we investigated whether MPE protects beta-cell function and studied the underlying mechanisms. We treateddb/dband 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 beta-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 thedb/dbmice but increased only insulin secretion in the HFD-induced obese mice. MPE substantially increased the beta-cell area in both models (3-fold and 2-fold,p< 0.01, fordb/dband HFD mice, respectively). We observed reduced nuclear translocation of the p65 subunit of NF-kappa B in islets of MPE-treated db/db mice, coinciding with enhanced glucose-stimulated insulin secretion (GSIS).In vitro, MPE potentiated GSIS and decreased interleukin 1 beta (IL-1 beta) secretion in MIN6 beta-cells. Incubation of MIN6 cells with tumor necrosis factor alpha (TNF alpha), interferon-gamma, and IL-1 beta amplified IL-1 beta secretion and inhibited GSIS. These effects were partially reversed with MPE or the I kappa B kinase beta inhibitor PS1145, coinciding with reduced activation of p65 and p-I kappa B in the NF-kappa B pathway. We conclude that MPE may have potential for therapeutic development for beta-cell protection.

涉及物种 沿阶草属 Ophiopogon