The anti-nephritic activity of a polysaccharide from okra (Abelmoschus esculentus (L.) Moench) via modulation of AMPK-Sirt1-PGC-1α signaling axis mediated anti-oxidative in type 2 diabetes model mice

Int J Biol Macromol. 2019 Nov 1:140:568-576. doi: 10.1016/j.ijbiomac.2019.08.149. Epub 2019 Aug 20.

Abstract

Diabetic nephropathy (DN) with high morbidity and mortality is one of the most severe diabetes complications and affects nearly one-third of people with diabetes. Our present experiment was designed to assess the potential therapeutic of a polysaccharide purified from okra (OP) on DN in high-fat diet-fed and streptozotocin (STZ)-induced diabetic mice. We found that an 8-week treatment with OP could significantly decrease the 24-h urine protein (24-h UP), serum creatinine (Scr), serum urea nitrogen (SUN) and glycosylated hemoglobin (HbA1c) levels, which are regard as the biomarkers of renal injury. The results of immunohistochemical analysis and histopathological examination showed that the diabetic-induced microstructural changes and fibrosis in kidney can be alleviated by the administration of OP (400 mg/kg). Our immunofluorescences results demonstrated that OP (400 mg/kg) could greatly reduce the level of reactive oxygen species (ROS) in kidney. In addition, we also studied the level of SOD, GSH, CAT, HO-1, Nrf2, p-AMPK, PGC-1α, Sirt1, Bcl-2, cleaved caspase-3 and Bax in renal tissue by assay kit and western blot. Our results suggested that OP ameliorated DN in diabetic mice, which is possibly related to suppressing apoptosis and oxidative stress through activating AMPK-Sirt1-PGC-1α signaling axis.

Keywords: A polysaccharide; Diabetic nephropathy; Okra.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Abelmoschus / chemistry*
  • Animals
  • Antioxidants / metabolism
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetic Nephropathies / metabolism
  • Disease Models, Animal
  • Fibrosis / drug therapy
  • Fibrosis / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Polysaccharides / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Sirtuin 1 / metabolism*
  • Streptozocin / pharmacology

Substances

  • Antioxidants
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Polysaccharides
  • Ppargc1a protein, mouse
  • Reactive Oxygen Species
  • Streptozocin
  • AMP-Activated Protein Kinases
  • Sirt1 protein, mouse
  • Sirtuin 1