Neuroprotective effects of anthocyanins and their in vivo metabolites in SH-SY5Y cells.
Recent in vivo studies have highlighted an important role for the neuroprotective actions of dietary anthocyanins. However, one consistent result of these studies is that the systemic bioavailability of anthocyanins, including cyanidin 3-O-glucopyranoside (Cy-3G), is very poor. Cy-3G has been demonstrated to be highly instable at physiological pH, so its in vivo metabolites, such as the aglycon cyanidin (Cy) and protocatechuic acid (PA), may be responsible for both the antioxidant activitiy and the neuroprotective effects observed in vivo. Therefore, we investigated the protective effects of Cy-3G, Cy and PA against H(2)O(2)-induced oxidative stress in a human neuronal cell line (SH-SY5Y). We determined their ability to counteract reactive oxygen species (ROS) formation and to inhibit apoptosis in terms of mitochondrial functioning loss and DNA fragmentation induced by H(2)O(2). We demonstrated that pretreatment of SH-SY5Y cells with Cy-3G, Cy and PA inhibits H(2)O(2)-induced ROS formation at different cellular levels: Cy-3G at membrane level, PA at cytosolic level and Cy at both membrane and cytosolic levels. In addition, Cy showed a higher antioxidant activity at membrane and cytosolic level than Cy-3G and PA, respectively. Interestingly, both Cy and PA, but not Cy-3G, could inhibit H(2)O(2)-induced apoptotic events, such as mitochondrial functioning loss and DNA fragmentation. These results suggest that Cy and PA may be considered as neuroprotective molecules and may play an important role in brain health promotion. These in vitro findings should encourage further research in animal models of neurological diseases to explore the potential neuroprotective effects of compounds generated during in vivo metabolism of anthocyanins.
Tarozzi
Andrea
A
Department of Pharmacology, Alma Mater Studiorum--University of Bologna,Via Irnerio 48, 40126 Bologna, Italy. andrea.tarozzi@unibo.it
Morroni
Fabiana
F
Hrelia
Silvana
S
Angeloni
Cristina
C
Marchesi
Alessandra
A
Cantelli-Forti
Giorgio
G
Hrelia
Patrizia
P
D000872:Anthocyanins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001927:Brain Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D045744:Cell Line, Tumor; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D062385:Hydroxybenzoates / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D000872:Anthocyanins; D000975:Antioxidants; D062385:Hydroxybenzoates; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C462279:cyanidin-3-O-beta-glucopyranoside; C009091:protocatechuic acid; C017154:cyanidin