title: Quercetin phospholipid complex significantly protects against oxidative injury in ARPE-19 cells associated with activation of Nrf2 pathway.
abstract: Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27μg/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400μM. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200μM. In addition, quercetin-PC at 200μM significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200μM failed to do so. Molecular examinations revealed that quercetin-PC at 200μM significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense.
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China. Electronic address: xinrong_xu@aliyun.com.
authors.forename: Xin-Rong
authors.initials: XR
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hang
authors.affiliation: Department of Clinical Laboratory, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Xue-Wen
authors.initials: XW
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Ding
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050217:Metabolic Detoxication, Phase II; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010743:Phospholipids / Q000737:chemistry*; D011794:Quercetin / Q000737:chemistry* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D010743:Phospholipids; D011794:Quercetin; D006861:Hydrogen Peroxide
keywords: Age-related macular degeneration; Nrf2; Oxidative stress; Phospholipid complex; Quercetin