Effects of α-mangostin on the apoptosis of mouse mesangial cells cultured with high glucose medium

Objective To investigate the effects of α-mangostin on the apoptosis of mouse mesangial cells (MES13) cultured with high glucose through inhibition of acid sphingomyelinase (ASMase) and endoplasmic reticulum stress signaling pathway. Methods Synchronized MES13 cells were divided into following group: a low glucose group (5.5 mmol/L glucose), a low glucose + α-mangostin group, a high glucose group (30 mmol/L glucose), a high glucose + low-concentration α-mangostin group (1 μmol/L), a high glucose + medium-concentration α-mangostin group (2 μmol/L), a high glucose+ high-concentration α-mangostin group (4 μmol/L), and a high glucose + desipramin group. The cell survival was detected by CCK-8 assay, and the cellular apoptosis was examined by flow cytometry. Moreover, the levels of ASMase, GRP78, p-PERK, ATF4, CHOP and caspase12 were detected by Western blot. Results Compared with the low glucose group, the apoptosis of MES13 cells in the high glucose group was significantly increased (P<0.05). Compared with the high glucose group, the apoptotic rate decreased in the high glucose+ α-mangostin group in a dose-dependent manner. Compared with the low glucose group, the levels of ASMase in MES13 cells in the high glucose group significantly increased (P<0.05). Compared with the high glucose group, the levels of ASMase decreased in the high glucose+ α-mangostin group (P<0.05). Compared with the low glucose group, the high glucose group produced remarkably increased levels of GRP78, p-PERK, ATF4, CHOP and caspase12 (P<0.05). Compared with the high glucose group, significant decreases were found in the levels of GRP78, p-PERK, ATF4, CHOP and caspase12 in the high glucose+ α-mangostin group (P<0.05). Conclusions α-Mangostin can inhibit the apoptosis of MES13 cells cultured with high glucose, through inhibiting the activation of ASMase by high glucose, and decreasing the inactivation of the endoplasmic reticulum stress signaling pathway, which provides experimental evidence for the prevention and control of diabetic nephropathy.