ABSTRACT
The effect of pepino polyphenolic extract (PPE) on diabetic neuropathy was examined. Using HPLC/ESI-MS-MS analysis, PPE was demonstrated to contain coumaroyl and caffeoyl derivatives among polyphenols. PPE at 0.5 or 1% was supplied to diabetic mice for 12 weeks. The PPE intake at two doses significantly improved glycaemic control. These treatments reserved the glutathione (GSH) level, and decreased the thiobarbituric acid reactive substances (TBARS) level, reactive oxygen species (ROS), interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, fructose, and glycation intermediates and precursors of advanced glycation end products (AGEs), such as methylglyoxal (MG) and N-(carboxymethyl)lysine (CML), in the sciatic nerves of diabetic mice. In a histological study of sciatic nerves, PPE had the effects in improving the nerves of diabetic mice, showing disorganization of the fascicle with numerous small myelinated fibers. The PPE intake at two doses retained the activity, and the protein and mRNA levels of glutathione peroxidase (GPX), and decreased protein expressions of aldose reductase (AR) and the receptor for the advanced glycation end product (RAGE) in sciatic nerves. These findings support that pepino polyphenolic extract could attenuate oxidative, inflammatory and glycative stress in diabetic peripheral nerves.
Subject(s)
Plant Extracts/pharmacology , Polyphenols/pharmacology , Sciatic Nerve/drug effects , Solanum/chemistry , Stress, Physiological/drug effects , Aldehyde Reductase/genetics , Aldehyde Reductase/metabolism , Animals , Blood Glucose/metabolism , Chromatography, High Pressure Liquid , Diabetes Mellitus, Experimental/drug therapy , Flavonoids/analysis , Gallic Acid/analysis , Glutathione Peroxidase/genetics , Glutathione Peroxidase/metabolism , Glycation End Products, Advanced/genetics , Glycation End Products, Advanced/metabolism , Hydroxybenzoates/analysis , Insulin/blood , Interleukin-6/blood , Male , Mice , Mice, Inbred BALB C , Oxidative Stress/drug effects , Plant Extracts/analysis , Polyphenols/analysis , Polysaccharides/analysis , Reactive Oxygen Species/metabolism , Sciatic Nerve/metabolism , Streptozocin , Tandem Mass Spectrometry , Tumor Necrosis Factor-alpha/bloodABSTRACT
Advances and improvements in mesenchymal stromal/stem cells (MSCs) and cell replacement therapies have been promising approaches to treat diabetes mellitus (DM) since their potent capacities for differentiation into various functional cells match the demands of tissue repair and regeneration. The aim of this study is to examine the effects of nano-sized type I collagen molecules in combination with nicotinamide (NCT) and exendin-4 (EX4) on MSC differentiation into insulin-secreting cells in vitro and to evaluate their reparative effects against type 2 diabetes mellitus (T2DM) in vivo. Differentiation of MSCs in the presence of NCT, nano-sized type I collagen molecules and EX4 was represented with insulin production and Nkx6.1/PDX-1 mRNA expression assessed by insulin secretion assay and quantitative RT-PCR. Histopathological and glycosylated haemoglobin (HbA1) analysis was performed to assess reparative effects against T2DM in the rat model. The results revealed that MSCs showed increased differentiation into insulin-secreting cells with higher mRNA expression for Nkx6.1 and early PDX-1 in the presence of NCT and nano-sized type I collagen molecules. Addition of nano-sized type I collagen fibrils increased morphologically islet-like clusters in differentiated cells. T2DM rats reverted to their normal HbA1 values and exhibited structurally repaired islets in the pancreas implanted with NCT/nano-sized collagen I molecule/EX4-incubated differentiated cells. In short, the combined recipe showed reparative actions on the destructive islet of Langerhans in the pancreas coupled with glucoregulatory effects in T2DM rats in vivo. Therefore, MSCs incubated with NCT/EX4 and nano-sized collagen I molecules could be a potential therapy for retrieval of destructed islets and could efficiently regulate blood glucose in T2DM.
