SGLT2 inhibitors prevent amyloid-beta induced brain endothelial cell integrity damage

SGLT2 (Sodium-glucose cotransporter 2) inhibitors are glucose-lowering drugs with multiple pleiotropic effects [1]. Recent studies suggest that they can also have neuroprotective properties [2].

The aim of the study was to assess the influence of SGLT2 inhibitors (empagliflozin, dapagliflozin and canagliflozin) on the integrity of HBMEC (Human Brain Microvascular Endothelial Cells) impaired with β-amyloid.

HBMEC were cultured for 24h, then stimulated with Medium (1), β-amyloid 4µM (2), β-amyloid with the presence of SGLT2 inhibitors empagliflozin 1µM (3), dapagliflozin 1µM (4), canagliflozin 1µM (5). The integrity of HMBEC was analyzed in the xCELLigence system and expressed as normalized Cell Index (nCI) after 4h.

The integrity of HBMEC stimulated with β-amyloid after 4h was 161.3% lower than medium control (nCI = -0.38±0.26 vs. 0.62 ±0.05), p=0.0003. The integrity of HBMEC stimulated with β-amyloid and empagliflozin 1µM was 202.6% higher than the integrity of β-amyloid only stimulated HBMEC (nCI= 0.39± 0.11 vs. -0.38±0.26), p=0.002. For dapagliflozin 1µM and β-amyloid it was 194.7% higher (nCI= 0.36± 0.02 vs. -0.38±0.26) p=0.0053. For canagliflozin this effect was 134.2% higher (nCI= 0.13± 0.26 vs. -0.38±0.26) 0.0223. There were no significant differences in the integrity of HBMEC incubated with β-amyloid + empagliflozin vs. medium (nCI = 0.39± 0.11 vs. 0.62 ±0.05), p=0.3776 and β-amyloid + dapagliflozin vs. medium (nCI = 0.36± 0.02 vs. 0.62 ±0.05), p=0.3837. For β-amyloid + canagliflozin the cellular integrity of HBMEC was significantly lower than the medium (nCI = 0.13± 0.26 vs. 0.62 ±0.05), p=0.0309 .

SGLT2 inhibitors attenuated HBMEC integrity loss induced by β-amyloid. For empagliflozin and dapagliflozin this effect was better than for canagliflozin as there was no difference in cellular integrity of HBMEC incubated with β-amyloid and empagliflozin or dapagliflozin vs medium control.