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

• Published in: International journal of biological macromolecules 2019-11, Vol.140, p.568-576
• Main Authors: Liao, Zhengzheng, Zhang, Jingying, Wang, Jinyu, Yan, Tingxu, Xu, Fanxing, Wu, Bo, Xiao, Feng, Bi, Kaishun, Niu, Jumin, Jia, Ying
• Format: Article
• Language: English
• Subjects: A polysaccharide; Abelmoschus - chemistry; AMP-Activated Protein Kinases - metabolism; Animals; Antioxidants - metabolism; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diabetic Nephropathies - metabolism; Diabetic nephropathy; Disease Models, Animal; Fibrosis - drug therapy; Fibrosis - metabolism; Kidney - drug effects; Kidney - metabolism; Male; Mice; Mice, Inbred C57BL; Okra; 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
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2019.08.149

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.