Molecular mechanism of naringenin inhibiting the expressions of inflammatory factors of mesangial cells in diabetic nephropathy

Abstract:

Objective：To study the effect of naringenin（NAR） on diabetic nephropathy（DN） mice and the expressions of inflammatory factors tumor necrosis factor alpha（TNF-α） and interleukin-6（IL-6） in glomerular mesangial cells. Methods：Totally 10 male db/db DN mice were randomly divided into two groups：NAR group and DN group. Five db/m control mice were set up as normal group. Mice in NAR group were treated with NAR [50 mg/（kg×d）] by gavage for two weeks. Mice in DN group were treated with the same volume of saline by gavage for two weeks. Mice in normal group were treated with normal diet. Body weight，blood glucose and urinary albumin excretion（UAE） were tested in mice，and the morphology of the renal glomerular was tested by HE staining and electron microscope. Moreover，the glomerular mesangial cells were cultured in DMEM medium with different glucose concentrations（5 mmol/L and 25 mmol/L glucose）. Cells in normal group were cultured with 5 mmol/L glucose. Cells in high glucose group were cultured with 25 mmol/L glucose. Cells in NAR group were cultured with 25 mmol/L glucose containing 400 μmol/L NAR. Then，the expressions of inflammatory factors TNF-α and IL-6 were tested by ELISA，and the expression of NF-κB p65 was tested by Western blot in the cytoplasm and nucleus of the cells. Results：After the treat－ment of NAR in mice，UAE was decreased[（51.48±8.54） μg/24 h] when compared with that in DN group[（99.3±5.15） μg/24 h]（F=254.302，P=0.000）；glomerular mesangial area was smaller[（2 098±571.84） μm2] than that in DN group[（4 240±536.66） μm2]（F=24.468，P=0.000），and the mesangial proliferation was lessened. Additionally，after the treatment of NAR in mesan－gial cells，the expressions of TNF-α and IL-6 were lower（1.99±0.29，1.76±0.15） than those in high glucose group（2.82±0.14，2.53±0.32）（F=111.303，P=0.000；F=65.127，P=0.000），the expression of NF-κB p65 was decreased（0.29±0.01） when compared with that in high glucose group（0.81±0.02）（F=1579.764，P=0.000）. Conclusion：Naringenin may play roles in relieving albu－minuria and mesangial proliferation via inhibiting the expressions of inflammatory factors through NF-κB in DN.