Luteolin attenuates diabetic nephropathy via inhibition of metalloenzymes in rats

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 glucoseinduced 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 streptozotocininduced diabetic nephropathy in rats by inhibiting MMP-2, MMP9, and HDAC-2 expression, and reducing oxidative stress and
inflammation.