Objective  To investigate the protective effect of apigenin on renal tubular epithelial cells (HK-2) induced by hyperglycemia and its potential mechanism.

Methods  HK-2 cells were incubated with d-glucose to establish an in vitro diabetic nephropathy model. Cell viability, apoptosis and oxidative stress were assessed. The mRNA levels of nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and epoxy chloropropane Kelch sample related protein-1 (Keap1) were measured by quantitative real-time-PCR (q-PCR). Western blot analysis was performed to measure the protein expression of Nrf2.

Results  In HK-2 cells, high glucose decreased cell viability in a concentration- and time-dependent manner. Apigenin improved the viability of HK-2 cells under high glucose stress, reduced apoptosis and proinflammatory cytokine production, and inhibited the oxidative stress. Apigenin increased mRNA expression of Nrf2 and HO-1, increased expression of Nrf2 protein and reduced the mRNA level of Keap1. Inhibition of Nrf2 using small interfering RNA (siRNA) abolished the protective effects of apigenin on HK-2 cells under high glucose stress.

Conclusion  Apigenin treatment can alleviate the damage of HK-2 cells under high glucose stress, and exert the anti-oxidation and anti-inflammation effects through Keap1-Nrf2-ARE pathway.

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