Eucommia ulmoides Cortex, Geniposide and Aucubin Regulate Lipotoxicity through the Inhibition of Lysosomal BAX

Abstract

In this study we examined the inhibition of hepatic dyslipidemia by Eucommia ulmoides extract (EUE). Using a screening assay for BAX inhibition we determined that EUE regulates BAX-induced cell death. Among various cell death stimuli tested EUE regulated palmitate-induced cell death, which involves lysosomal BAX translocation. EUE rescued palmitate-induced inhibition of lysosomal V-ATPase, α-galactosidase, α-mannosidase, and acid phosphatase, and this effect was reversed by bafilomycin, a lysosomal V-ATPase inhibitor. The active components of EUE, aucubin and geniposide, showed similar inhibition of palmitate-induced cell death to that of EUE through enhancement of lysosome activity. Consistent with these in vitro findings, EUE inhibited the dyslipidemic condition in a high-fat diet animal model by regulating the lysosomal localization of BAX. This study demonstrates that EUE regulates lipotoxicity through a novel mechanism of enhanced lysosomal activity leading to the regulation of lysosomal BAX activation and cell death. Our findings further indicate that geniposide and aucubin, active components of EUE, may be therapeutic candidates for non-alcoholic fatty liver disease.

Aucubin Protects against Myocardial Infarction‐Induced Cardiac Remodeling via nNOS/NO‐Regulated Oxidative Stress

“…By inhibition of NF- κ B signaling, aucubin prevents proinflammatory cytokine-induced inflammatory response [ 6 , 7 ]. Aucubin is also reported to regulate Bcl-2 family protein expression and inhibit cell death [ 12 ] and apoptosis [ 8 , 9 ]. Ho et al reported that aucubin protected against UVB-induced skin fibroblast activation by inhibition of the production of matrix metalloproteinase-1 [ 13 ].…”

Aucubin Protects against TGFβ1-Induced Cardiac Fibroblasts Activation by Mediating the AMPKα/mTOR Signaling Pathway

“…plants Plantago lanceolata L. and Veronica officinalis L. (Plantaginaceae). Several pharmacological benefits have been reported for aucubin, such as hepatoprotective [7], anti-inflammatory [8], anti-oxidant [9,10], anti-osteoporosis [11], and neurotrophic effects [12,13]. Lv et al [14] reported that aucubin reduced the protein expression of α-SMA, collagen I, collagen III, and MMP-2, suppressed the generation of reactive oxygen species, and down-regulated the nicotinamide adenine dinucleotide phosphate-oxidase-4 mRNA expression in LX-2 cells.…”

Citrus Peel Extract Ameliorates High-Fat Diet-Induced NAFLD via Activation of AMPK Signaling

“…Citrus flavonoids have antioxidant, anti-inflammatory, and antitumor activities [2,16]. Hesperidin, a major compound of citrus peel [29], suppresses cell death through regulation of AMPK activation [30]. Along with other components in citrus peel, mTOR was inhibited by hesperidin.…”