Luteolin attenuates diabetic nephropathy via inhibition of metalloenzymes in rats  

作　　者：R.B.Daude Rajendra Bhadane J.S.Shah 

机构地区：[1]Department of Pharmacy,Government Polytechnic,Jalgaon-425001,Maharashtra,India [2]Structural Bioinformatics Laboratory,Faculty of Science and Engineering,Biochemistry,Abo Akademi University,FI-20520 Turku,Finland [3]Pharmaceutical Sciences Laboratory,Faculty of Science and Engineering,Pharmacy,Åbo Akademi University,FI-20520 Turku,Finland [4]Institute of Biomedicine,Research Unit for Infection and Immunity,University of Turku,FI-20520 Turku,Finland [5]Department of Pharmacology,Institute of Pharmacy,Nirma University,Ahmedabad-382481,Gujrat,India

出　　处：《Asian Pacific Journal of Tropical Biomedicine》2023年第12期507-520,I0002,I0003,共16页亚太热带生物医学杂志（英文版）

基　　金：supported by the Joe,Pentti,and Tor Borg Memorial Fund.

摘　　要：Objective:To investigate the renoprotective effects of luteolin on diabetes in rats.Methods:One week after administration of streptozotocin 55 mg/kg intraperitoneally,rats were given 25,50,and 75 mg/kg/day of luteolin orally for another eight weeks.At the end of the experiment,body weight,blood glucose level,biochemical parameters for renal function(serum creatinine,blood urea nitrogen,uric acid,serum albumin,and total protein),kidney histology,matrix metalloproteinase(MMP)-2,MMP-9,and histone deacetylase 2(HDAC-2)expression,and malondialdehyde,myeloperoxidase,and hydroxyproline content in renal tissue were evaluated.High glucose-induced damage using NRK-52E cell line was studied to evaluate cell viability and metalloenzyme expression.Additionally,in silico studies including docking and molecular dynamics simulations were conducted.Results:MMP-2,MMP-9,and HDAC-2 expressions were significantly increased in high glucose-induced NRK-52E cells and the renal tissue of diabetic rats.However,these changes were reversed by luteolin at the administered doses.Additionally,luteolin significantly reduced oxidative stress,inflammation,and fibrosis,as well as improved biochemical parameters in diabetic rats.Furthermore,luteolin at the examined doses markedly alleviated diabetes-induced histopathological changes in renal tissues.Conclusions:Luteolin effectively attenuates streptozotocin-induced diabetic nephropathy in rats by inhibiting MMP-2,MMP-9,and HDAC-2 expression,and reducing oxidative stress and inflammation.

关 键 词：MMPS HDAC-2 LUTEOLIN NRK-52E Diabetic nephropathy DOCKING Molecular dynamic simulations 

分 类 号：R285.5[医药卫生—中药学]