Mangiferin protects mitochondrial function by preserving mitochondrial hexokinase-II in vessel endothelial cells

Abstract

Hexokinase-II (HK-II) confers protection against cell death and this study was designed to investigate the effect of mangiferin on the regulation of mitochondrial HK-II. In vessel endothelial cells, saturated fatty acid palmitate (PA) stimulation induced HK-II detachment from mitochondria due to cellular acidification. Mangiferin reduced lactate accumulation by improving pyruvate dehydrogenase activity, promoted Akt translocation to HK-II and prevented HK-II detachment from mitochondria. Knockdown of Akt2 diminished the protective effect of mangiferin on mitochondrial HK-II, confirming the role of Akt in the regulation of HK-II. Mangiferin prevented mitochondrial permeability transition pore opening, restored mitochondrial membrane potential and thereby protected cell from apoptosis. In high-fat diet fed mice, oral administration of mangiferin induced Akt phosphorylation, increased HK-II binding to mitochondria and resultantly protected vessel endothelial function, demonstrating its protective effect on endothelial integrity in vivo. This finding provided a novel strategy for the protection of mitochondrial function in the endothelium.

Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation

“…In addition, in an in vitro research, Song J. et al . had made a systemic investigation of the detail effect of MF on mitochondrial function, and demonstrated that MF could reduce Cyto C release and further protect cell from apoptosis by inhibiting capase-3 activation, resulting from its prevention against mitochondrial membrane potential and its restoration of mitochondrial membrane potential 52 . In the present study, we observed similar beneficial effects of MF on mitochondrial Cyto C release and related apoptosis in SAH rats, which provide us some primary evidences to deduce the mitochondrial role in MF’s neuroprotection.…”

Mangiferin Ameliorates Cisplatin Induced Acute Kidney Injury by Upregulating Nrf-2 via the Activation of PI3K and Exhibits Synergistic Anticancer Activity With Cisplatin

“…In the flavonoid family, mangiferin, a non-steroidal polyhydroxy polyphenolic molecule, found predominantly in the bark of the Mangifera indica , has pleotropic activity ( Pal et al, 2013 , 2014 ). It has free radical scavenging activity and can inhibit as well as ameliorate ROS induced oxidative damage against several pathophysiological conditions ( Ghosh et al, 2012 ; Matkowski et al, 2013 ; Song et al, 2017 ). Previous studies indicated that pretreatment of renal cells with mangiferin prevents oxidative damage induced by tert-Butyl hydroperoxide (tBHP) via modulating the PI3K-AKT mediated signaling pathway and activation of Nrf-2 ( Saha et al, 2016c ).…”

Upregulation of CFTR Protects against Palmitate-Induced Endothelial Dysfunction by Enhancing Autophagic Flux

“…The mitochondrial apoptotic signaling pathway is associated with mitochondrial dysfunction: decreased mitochondrial membrane potential, and proapoptotic Bcl-2 family member translocation from cytosol to mitochondria leading to the release of Cyt C, and subsequently causes the activation of caspase 9 apoptotic caspase cascade [ 45 ]. It was reported that PA induced endothelial cell apoptosis by stimulating the death receptor pathway mediated by the TNF-R1/TNFR1-associated death domain protein (TRADD)/caspase 8 pathway [ 46 ], whereas most studies showed that PA led to mitochondrial dysfunction and increased the protein levels of Bax, Cyt C, and cleaved caspase 9 but reduced Bcl-2 protein expression [ 13 , 47 – 49 ]. In our previous study, we found that PA induced apoptosis in HUVECs through the mitochondria-mediated signaling pathway showing as a decrease of mitochondrial membrane potential and the ratio of Bcl-2/Bax [ 6 ].…”