title: Calycopterin promotes survival and outgrowth of neuron-like PC12 cells by attenuation of oxidative- and ER-stress-induced apoptosis along with inflammatory response.
abstract: There is mounting evidence implicating the role of oxidative stress induced by reactive oxygen species (ROS) in neurodegenerative disease, including Alzheimer's disease. Herein we investigated the neuroprotective potential of a natural flavonoid, calycopterin, against H(2)O(2)-induced cell death in differentiated PC12 cells. We pretreated PC12 cells with 25, 50, and 100 μM calycopterin followed by the addition of H(2)O(2) as an oxidative stress agent. We measured cell viability by the MTT test and found that 50 μM is the best protective concentration of calycopterin. Moreover, we measured six different parameters of neurite outgrowth. Interestingly, we found that calycopterin not only protects PC12 cells against H(2)O(2)-induced apoptosis but also defends against the destructive effect of oxidative stress on the criteria of neural differentiation. Calycopterin decreased ER stress-associated proteins including calpain and caspase-12, and suppressed ERK, JNK, and p38 MAPK phosphorylation. Moreover, calycopterin inhibited H(2)O(2)-induced nuclear translocation of nuclear factor-κB, a known regulator of a host of genes involved in specific stress and inflammatory responses. This observation was perfectly in agreement with the decrease of COX-2 and TNF-α levels. Calycopterin reduced intracellular ROS levels and increased catalase activity. The protective effect of this compound could represent a promising approach for the treatment of neurodegenerative diseases.
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran.
authors.forename: Mahdi Moridi
authors.initials: MM
authors.lastname: Farimani
authors.forename: Nazanin Namazi
authors.initials: NN
authors.lastname: Sarvestani
authors.forename: Niloufar
authors.initials: N
authors.lastname: Ansari
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002154:Calpain / Q000378:metabolism; D053454:Caspase 12 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D047309:Flavones; D014409:Tumor Necrosis Factor-alpha; C533734:calycopterin; D006861:Hydrogen Peroxide; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002154:Calpain; D053454:Caspase 12