Page 44 - ebook

[B. Cell Biology/Stem Cell] B-22

Ginsenoside protopanaxadiol-induced changes in autophagy

and apoptosis in chloroquine-induced adult retinal pigment

epithelial-19 cells

Haesung Lee¹, Long Ngo Hoang¹, Ngoc Buu Tran¹, Sook-Jeong Lee¹*

¹Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National

University, Jeonju, Jeollabuk-do 54896, Korea

Ginsenosides are the major active component found in ginseng (Panax ginseng). Among the ginsenosides, (20S)-

Protopanaxadiol (PPD) ginsenosides Rg3, Rh2 have been demonstrated for their hepatoprotection, tumor
suppression and diabetes resistance. Chloroquine (CQ) is an antimalarial drug known to inhibit autophagy flux by

impairing autophagosome–lysosome fusion, frequently causes serious eye and vision problems. In this study, we
dertermined whether the PPD reduces CQ-induced retinopathy by restoring lysosomotropic abnormalities in human

adult retinal pigment epithelial (ARPE)-19 cells. The accumulation of autophagosomes with fusion defects in
lysosomes and the formation of ROS in CQ-treated ARPE-19 cells, which trapped Beclin-1 with B-cell lymphoma 2

(Bcl-2), interfering with autophagy initiation and autophagosome development. PPD alleviated the CQ-induced
toxicity by modulating the interaction between Beclin-1 and Bcl-2, and this effect was mediated by the 5' adenosine
monophosphate-activated protein kinase-mammalian target of rapamycin signal axis. The results indicate that

autophagy and apoptosis were simultaneously controlled by PPD via the upregulation of autophagy flux and

decreased ROS formation and apoptotic protein expression. These findings suggest that PPD may be a promising
treatment strategy for CQ-mediated retinopathy.