title: Neuroprotective effect of Salvia sahendica is mediated by restoration of mitochondrial function and inhibition of endoplasmic reticulum stress.
abstract: Herein, we investigated the protective effect of Salvia sahendica against H(2)O(2)-induced cell death in rat pheochromocytoma (PC12) cells. Our data show that S. sahendica blocks apoptosis pathway by inhibition of cytochrome c release from mitochondria and leakage of calcium from endoplasmic reticulum. It also activates/inactivates two members of Bcl-2 family, Bax and Bcl-2. Bax inhibition and Bcl-2 activation suppress release of cytochrome c from mitochondria that prevents cleavage of caspase-3. Besides S. sahendica suppresses ER stress via attenuation of intracellular levels of calcium. Suppression of ER stress decreased calpain activation and subsequently cleavage of caspase-12. Altogether, these results indicate that S. sahendica protects PC12 cells treated with H(2)O(2) via suppression of upstream factors of apoptosis pathway. While oxidative stress is an early event in Alzheimer disease, it seems that S. sahendica prevents deleterious effects of reactive oxygen species by stabilizing mitochondrial membranes and inhibiting ER stress.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaerzadeh
authors.forename: Shabnam Zeighamy
authors.initials: SZ
authors.lastname: Alamdary
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Esmaeili
authors.forename: Nazanin Namazi
authors.initials: NN
authors.lastname: Sarvestani
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000096:biosynthesis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D016923:Cell Death / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006861:Hydrogen Peroxide; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010936:Plant Extracts / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D027544:Salvia / Q000737:chemistry*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000187:drug effects
chemical_list: D061945:Caspase Inhibitors; D018696:Neuroprotective Agents; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D006861:Hydrogen Peroxide; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D002154:Calpain; D053148:Caspase 3; D002118:Calcium