Protective effect of 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione, isolated from Averrhoa carambola L., against Aβ1–42-induced apoptosis in SH-SY5Y cells by reversing Bcl-2/Bax ratio

• DOI: 10.1007/s00213-020-05668-9
• Publication Date: 2020-10-08T04:02:43Z
• Authors: Shunyu Lu; Xiaojie Wei; Hongliang Zhang; Zhenfeng Chen; Juman Li; Xiaohui Xu; Qiuqiao Xie; Lixiu Chen; Fangxing Ye; Hoa Thi Thai Phama; Luhui Jiang; Tianmin Huang; Jinbin Wei; Renbin Huang
• Keywords: Bcl-2-associated X protein; SH-SY5Y

Aβ1-42-induced neurotoxicity has been considered as a possible mechanism to aggravate the onset and progression of Alzheimer's disease (AD). In this study, we aim to determine the protective effect of DMDD on the apoptosis of SH-SY5Y cells induced by Aβ1-42 and elucidate potential mechanism of DMDD's protective function in apoptosis.CCK-8, AnnexinV-FITC/PI flow cytometry, and transmission electron microscopy analysis were used to determine the protection of DMDD on Aβ1-42-evoked apoptosis of SH-SY5Y cells. Cytochrome c release, JC-1 staining, and measuring the protein of Bcl-2 family by Western blot were applied to elucidate the mechanism of DMDD's protective function in apoptosis.Three concentration of DMDD (5 μmol/L, 10 μmol/L, and 20 μmol/L) rescues the cell viability loss and apoptosis of SH-SY5Y cells cultivated in Aβ1-42. The expressions of cleaved Caspase-3, -8, -9, the cytochrome c release, and mitochondrial membrane potential loss were inhibited by DMDD in Aβ1-42-insulted SH-SY5Y cells. The Western blot analysis showed that DMDD pretreatment clearly downregulated the protein of Bax and upregulated Bcl-2. Moreover, the Bcl-2/Bax ratio was obviously decreased in cells only exposed to Aβ1-42, but, which was suppressed by treated with DMDD.DMDD attenuated the apoptosis of SH-SY5Y cells induced by Aβ1-42 through reversing the Bcl-2/Bax ratio.